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Here is a chemical reaction formula: Reactants are aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br, amount is: 0.0033400000538676977 MOLE;amine:C1CN(CCN1)CCC2=CC=CC=N2, amount is: 0.0035099999513477087 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.004350000061094761 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.00033400001120753586 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00016700000560376793 MOLE.Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC=CC=N4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 12/01 2009 15:21:58 +0100 To ethyl 7-bromobenzofuran-2-carboxylate (0.900 g, 3.34 mmol) and 1-(2-(pyridin-2-yl)ethyl)piperazine (0.672 g, 3.51 mmol) in dry degassed dioxane (13 mL) were added Cesium carbonate (1.417 g, 4.35 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.159 g, 0.33 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.153 g, 0.17 mmol) under argon and the reaction heated at 95°C o/n. All starting material consumed. Water and DCM were added and the layers separated. The aq phase was extracted with DCM (3x). The combined org phases were washed with water, dried (MgSO4), filtered and evaporated. The crude was purified by flash chrom. (SiO2; DCM/MeOH 95/5) to give EN02198-25-001: 47.3 mg (fraction 12 from the flash) of the product as a pale yellow solid. This batch was submitted to test. EN02198-25-002: 0.460 g (fractions 11 and 13-18 from the flash) of the product as a pale brown solid. |
Here is a chemical reaction formula: Reactants are amine:C1CN(CCN1)CCC2=CC=CC=N2, amount is: 0.005849999841302633 MOLE;aryl halide:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)Br, amount is: 0.005570000037550926 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.007249999791383743 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 0.0005569999921135604 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0002789999998640269 MOLE.Products are 0:CCOC(=O)C1=CC2=C(O1)C(=CC=C2)N3CCN(CC3)CCC4=CC=CC=N4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 17/02 2009 12:47:13 +0100 To ethyl 7-bromobenzofuran-2-carboxylate (1.50 g, 5.57 mmol) and 1-(2-(pyridin-2-yl)ethyl)piperazine (1.120 g, 5.85 mmol) in dry degassed dioxane (20 mL) were added Cesium carbonate (2.361 g, 7.25 mmol), 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.266 g, 0.56 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.255 g, 0.28 mmol) under argon and the reaction heated at 95°C o/n. The reaction was allowed to reach rt. Starting material left 18/02 2009 14:51:20 +0100 Additional2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (0.266 g, 0.56 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.255 g, 0.28 mmol) were added and the reaction stirred at 95°C o/n. The reaction mixture was pooled with the reaction mixture in EN02198-44. Water and DCM were added and the layers separated. The aq phase was extracted with DCM (3x). The combined org phases were washed with water, dried (Na2SO4), filtered and evaporated. The crude was purified by flash chrom. (SiO2; DCM/MeOH 95/5) to give 1.48 g (35% calculated from EN02198-44+45) of the product as a pale brown solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)COC2=CN=C(C=C2)Cl, amount is: 0.009530000388622284 MOLE;amine:CC(C)(C)OC(=O)N1CCNCC1, amount is: 0.010499999858438969 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.013299999758601189 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 9.529999806545675e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 9.529999806545675e-05 MOLE.Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=NC=C(C=C2)OCC3=CC=CC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: BIS(DIBENZYLIDENEACETONE)PALLADIUM (0.055 g, 0.10 mmol) was added to tert- butyl piperazine-1-carboxylate (1.952 g, 10.48 mmol), 5-(benzyloxy)-2-chloropyridine (2.093 g, 9.53 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.059 g, 0.10 mmol) and sodium 2-methylpropan-2-olate (1.282 g, 13.34 mmol) in toluene (30 mL) at 20ºC under nitrogen. The resulting solution was stirred at 80 °C for 16 hours then cooled to room temperature. The reaction mixture was filtered through celite, filtrate partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase was dried (Na2SO4), filtered and evaporated to give a brown gum. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(5-(benzyloxy)pyridin-2-yl)piperazine-1-carboxylate (2.420 g, 68.7 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=CC(=C1)OC(F)(F)F)C2=CN=C3N2N=C(C=C3)Cl.Cl, amount is: 0.0015699999639764428 MOLE;amine:CN1CCC(CC1)CN, amount is: 0.002360000042244792 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.006279999855905771 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4, amount is: 0.0004710000066552311 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00015700000221841037 MOLE.Products are 0:CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A 100 mL round bottom flask was charged with a magnetic stir bar, toluene (17.45 mL), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine hydrochloride (550 mg, 1.57 mmol) (EN02141-06), Pd2dba3 (144 mg, 0.16 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (185 mg, 0.47 mmol),sodium tert-butoxide (604 mg, 6.28 mmol), and (1-methylpiperidin-4-yl)methanamine (302 mg, 2.36 mmol). The mixture was degassed with argon, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 110 °C with stirring for 16 h. The mixture was cooled to rt, pre-absorbed onto silca gel (~ 10 g) and purified on silica gel (80 g) using MeOH/DCM (1:3) as eluent to afford the title compound, .N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (391 mg, 55.6 %) as an off white solid. 110 mg of this pure free base was dissolved in anhydrous MeOH and 32 uL of conc. H2SO4 were added. The mixture was stirred for 10 min. ar rt before being conc. in vacuo. The crude solids were triturated with diethyl ether and collected via vacuum filtration to afford the title compound as its bis(bisulfate). |
Here is a chemical reaction formula: Reactants are amine:C1COCCN1, amount is: 0.009829999879002571 MOLE;aryl halide:CCOC(=O)C1=C(C2=CC(=C(C=C2N=C1)OCCOC)Br)NC3=C(C=C(C=C3)C)F, amount is: 0.009829999879002571 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.029500000178813934 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0031399999279528856 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0007859999896027148 MOLE.Products are 0:CCOC(=O)C1=C(C2=CC(=C(C=C2N=C1)OCCOC)N3CCOCC3)NC4=C(C=C(C=C4)C)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Reaction reference EN00057-06, EN02095-49, 67, 68, 74, 78, 90 In a 50 mL round-bottomed flask was ethyl 6-bromo-4-(2-fluoro-4-methylphenylamino)-7-(2-methoxyethoxy)quinoline-3-carboxylate (4.6911 g, 9.83 mmol), Morpholine (0.857 mL, 9.83 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.720 g, 0.79 mmol), and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (1.958 g, 3.14 mmol) in Dioxane (100 mL) to give a orange suspension. The reaction mixture was heated and stirred at 80°C (start 4pm). After stirring/heating overngiht, reaction is about 30% complete. Add rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (1.958 g, 3.14 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.720 g, 0.79 mmol). Continue heating/stirring. After heating and stirring for another 24hr, reaction is about 85% complete with some starting material. Add rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (1.958 g, 3.14 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.720 g, 0.79 mmol). Continue heating and stirring. Reaction complete after going another 24 hr. Cool reaction, and concentrate in vacuo (CIV). Dissolve in DCM, and purify on ISCO; EtOAc/Hexanes, 0-100%, some product elutes at end of run. Continue eluting column with MeOH/DCM, 0-5%; more product elutes at 5%. Combine all fractions containing product; 3.5475g isolated of an amber solid. LC-MS and NMR indicate that it is a mixture of methyl and ethyl ester products. |
Here is a chemical reaction formula: Reactants are amine:C[C@@H]1CN(CCN1)C(=O)OC(C)(C)C, amount is: 0.0003000000142492354 MOLE;aryl halide:C1=CC=C(C=C1)COC2=CC=C(C=C2)Br, amount is: 0.0006000000284984708 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.00033000000985339284 MOLE,Solvents are Solvent:C1CCOC1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 0.00033000000985339284 MOLE;metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Pd], amount is: 2.9999999242136255e-05 MOLE.Products are 0:C[C@@H]1CN(CCN1C2=CC=C(C=C2)OCC3=CC=CC=C3)C(=O)OC(C)(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 1-(benzyloxy)-4-bromobenzene (158 mg, 0.60 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (60.1 mg, 0.3 mmol), bis(tri-t- butylphosphine)palladium(0) (15.33 mg, 0.03 mmol) and potassium tert-butoxide (37.0 mg, 0.33 mmol) in THF (2 mL) was flushed with nitrogen and sealed into a microwave tube. The reaction was heated to 150 °C for 20 minutes in the microwave reactor and cooled to RT. The reaction mixture was filtered and the filtrate evaporated to dryness. The residue was dissolved in MeOH (5mL) and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 0.35M NH3/MeOH and pure fractions were evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-methylpiperazine-1-carboxylate (41.0 mg, 35.7 %) as a colourless oil that solidified on standing. |
Here is a chemical reaction formula: Reactants are amine:C[C@@H]1CN(CCN1)C(=O)OC(C)(C)C, amount is: 0.0003000000142492354 MOLE;aryl halide:C1=CC=C(C=C1)COC2=CC=C(C=C2)Br, amount is: 0.0003600000054575503 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.00044999999227002263 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 2.4000000848900527e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.9999999242136255e-05 MOLE.Products are 0:C[C@@H]1CN(CCN1C2=CC=C(C=C2)OCC3=CC=CC=C3)C(=O)OC(C)(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of (R)-tert-butyl 3-methylpiperazine-1-carboxylate (0.060 g, 0.3 mmol), 1-(benzyloxy)-4-bromobenzene (0.095 g, 0.36 mmol), palladium(II) acetate (6.74 mg, 0.03 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.015 g, 0.02 mmol) and sodium t-butoxide (0.043 g, 0.45 mmol) in toluene (2 mL) was flushed with nitrogen and sealed into a microwave tube. The reaction was heated to 150 °C for 10 minutes in the microwave reactor and cooled to RT. Analysis by LCMS. Only a small amount of the product could be detected (MH+ = 383, 5%). The reaction was not progressed further. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)COC2=CC=C(C=C2)Br, amount is: 0.003000000026077032 MOLE;amine:C[C@@H]1CN(CCN1)C(=O)OC(C)(C)C, amount is: 0.001500000013038516 MOLE,Reagents are Base:CC(C)(C)[O-].[K+], amount is: 0.0016499999910593033 MOLE,Solvents are Solvent:C1CCOC1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 0.0001500000071246177 MOLE;metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C.[Pd], amount is: 0.0001500000071246177 MOLE.Products are 0:C[C@@H]1CN(CCN1C2=CC=C(C=C2)OCC3=CC=CC=C3)C(=O)OC(C)(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of 1-(benzyloxy)-4-bromobenzene (789 mg, 3.00 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (300 mg, 1.5 mmol), bis(tri-t- butylphosphine)palladium(0) (77 mg, 0.15 mmol) and potassium tert-butoxide (185 mg, 1.65 mmol) in THF (10 mL) was flushed with nitrogen and heated to 75 °C overnight. A further 0.1eq of bis(tri-t-butylphosphine)palladium(0) (77 mg, 0.15 mmol) was added and the reaction was heated for a further 2.5 hours. The solvent was evaporated and the residue dissolved in MeOH (10mL) and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 0.35M NH3/MeOH and purified further by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-methylpiperazine-1-carboxylate (181 mg, 31.5 %) as an orange oil. |
Here is a chemical reaction formula: Reactants are amine:C[C@@H]1CN(CCN1)C(=O)OC(C)(C)C, amount is: 0.0003600000054575503 MOLE;aryl halide:C1=CC=C(C=C1)COC2=CC=C(C=C2)Br, amount is: 0.0003000000142492354 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0010499999625608325 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 5.999999848427251e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.9999999242136255e-05 MOLE.Products are 0:C[C@@H]1CN(CCN1C2=CC=C(C=C2)OCC3=CC=CC=C3)C(=O)OC(C)(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of (R)-tert-butyl 3-methylpiperazine-1-carboxylate (0.072 g, 0.36 mmol), 1-(benzyloxy)-4-bromobenzene (0.079 g, 0.3 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.035 g, 0.06 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.027 g, 0.03 mmol) and sodium 2-methylpropan-2-olate (0.101 g, 1.05 mmol) in toluene (2 mL) was flushed with nitrogen and sealed into a microwave tube. The reaction was heated to 150 °C for 10 minutes in the microwave reactor and cooled to RT. Only a small amount of the desired product was visible by LCMS. The reaction was not progressed further. |
Here is a chemical reaction formula: Reactants are amine:C1CCNCC1, amount is: 0.0005949999904260039 MOLE;aryl halide:C1=CC(=C(C=C1Br)F)C#N, amount is: 0.0005949999904260039 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0005949999904260039 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 2.970000059576705e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.970000059576705e-05 MOLE.Products are 0:C1CCN(CC1)C2=CC(=C(C=C2)C#N)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 4-bromo-2-fluorobenzonitrile (119 mg, 0.59 mmol), Piperidine (0.059 mL, 0.59 mmol), Palladium(II) acetate (6.68 mg, 0.03 mmol), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (14.18 mg, 0.03 mmol) and sodium tert-butoxide (57.2 mg, 0.59 mmol) were suspended in toluene (4 mL) and tBuOH (0.800 mL) and heated to 160°C for 10 minutes in the microwave. LCMS indicated incomplete reaction, thus, the reaction mixture was heated to 160°C for a further 20 minutes. Still incomplete reaction however, the reaction mixture was diluted with EtOAc (10 mL), and washed sequentially with water (10 mL), and saturated brine (10 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. A yellow oil (60mg) was isolated but NMR revealed this not be the desired product. No further work done. |
Here is a chemical reaction formula: Reactants are amine:C1=CN=CC=C1C2=CC3=CN=C(N=C3C(=C2)Cl)N, amount is: 0.012000000104308128 MOLE;aryl halide:C[C@H](C1=CC=C(C=C1)Br)NC(=O)OC(C)(C)C, amount is: 0.014700000174343586 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.017100000753998756 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0002680000034160912 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0001250000059371814 MOLE.Products are 0:C[C@H](C1=CC=C(C=C1)NC2=NC=C3C=C(C=C(C3=N2)Cl)C4=CC=NC=C4)NC(=O)OC(C)(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A 250 mL roundbottom flask was charged with 8-chloro-6-(pyridin-4-yl)quinazolin-2-amine (EN01547-76-1; 3.09 g, 12.04 mmol), (R)-tert-butyl 1-(4-bromophenyl)ethylcarbamate (EN01547-74-1; 4.42 g, 14.72 mmol), Pd2(dba)3 (114.4 mg, 2.1 mol % Pd), XantPhos (155.0 mg, 2.2 mol %), and Cs2CO3 (5.57 g, 17.10 mmol). The flask was evacuated and backfilled with N2 (3x), and then anhydrous dioxane (40 mL) was added. The mixture was allowed to stir at room temperature for ~5 minutes and was then heated under N2 in a 100 °C oil bath. After heating overnight, LC-MS showed complete conversion of the starting material to the desired product (trace N-phenylated product). A significant side product appeared to be present, derived from the starting aminoquinazoline that had undergone two Suzuki couplings in the previous step (see EN01547-76; MW=518.6). The reaction was allowed to cool and was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc, and the combined organics were concentrated under reduced pressure. The crude material was purified by silica gel chromatography (Rf in EtOAc = 0.44) to give a yellow-orange solid. 2.92 g (51%) of solid was collected. A trace of EtOAc remained by NMR analysis despite being kept under high vacuum over the weekend. |
Here is a chemical reaction formula: Reactants are amine:CC1=C(C=CC(=N1)N2C=NC=N2)N, amount is: 0.028200000524520874 MOLE;aryl halide:CC(C)OC(=O)N1CCC(CC1)OC2=C(C(=NC=N2)Cl)OC, amount is: 0.028200000524520874 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0005629999795928597 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)CN1CCN2CCN(P1N(CC2)CC(C)C)CC(C)C, amount is: 0.0005629999795928597 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00028199999360367656 MOLE.Products are 0:CC1=C(C=CC(=N1)N2C=NC=N2)NC3=C(C(=NC=N3)OC4CCN(CC4)C(=O)OC(C)C)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Sodium tert-butoxide (8.28 mL, 67.61 mmol) was added portionwise to a mixture of 2-methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-amine (4.94 g, 28.17 mmol) isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (9.29 g, 28.17 mmol) and in dioxane (136 mL) at 18°C over a period of 1 minute under nitrogen. The mixture was degassed by subjecting to vacuum then nitrogen atmosphere (six times). Palladium(II) acetate (0.063 g, 0.28 mmol) and 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo{3.3.3}undecane (0.200 mL, 0.56 mmol) was added and the mixture degassed again. The resulting suspension was stirred at 90 °C for 3 hours. Palladium(II) acetate (0.126 g, 0.56 mmol) and 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo{3.3.3}undecane (0.400 mL, 1.12 mmol) was added and the reaction stirred at 90 °C for 5 hours. The reaction mixture was diluted with water (100 mL) then extracted with EtOAc (300 mL), and washed with saturated brine (100 mL). The aqueous was extracted with EtOAc ( 100 mL). The combined organic layers were dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography (330g column), elution gradient 0 to 10% EtOH in DCM (rising quickly to 5% then more slowly to 10%). Pure fractions were evaporated to dryness to afford impure isopropyl 4-(5-methoxy-6-(2-methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-ylamino)pyrimidin-4-yloxy)piperidine-1-carboxylate, EN02029-80-P, as a yellow solid. The chromatography was repeated to give a slightly purer sample, EN02029-80-P2. This was triturated with Et2O (40 mL) to give a mobile solid which was filtered off and washed with Et2O (2 x 10 mL) then hexane (2 x 10 mL) to give a pale yellow solid, EN02029-80-solid 1. Analysis of this compound showed good purity so this mobile pale yellow solid was handed in as EN02029-80-01. |
Here is a chemical reaction formula: Reactants are amine:CC(=O)N1CCN(CC1)C2=C(C=C(C(=C2)OC)N)OC, amount is: 0.0005000000237487257 MOLE;aryl halide:C1=CC2=NC=C(N2C=C1)C3=NC(=NC=C3Cl)Cl, amount is: 0.0005000000237487257 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 3.9999998989515007e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 3.9999998989515007e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.9999999494757503e-05 MOLE.Products are 0:CC(=O)N1CCN(CC1)C2=C(C=C(C(=C2)OC)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC=C5)Cl)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: _3-(2,5-dichloropyrimidin-4-yl)imidazo[1,2-a]pyridine (132.5 mg, 0.50 mmol)_ _ _ _1-(4-(4-amino-2,5-dimethoxyphenyl)piperazin-1-yl)ethanone (140 mg, 0.50 mmol)_ ___(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (23.14 mg, 0.04 mmol)_ _ _ _cesium carbonate (244 mg, 0.75 mmol)_ ___diacetoxypalladium (4.49 mg, 0.02 mmol)_ _were suspended in_ _1,4-dioxane (4 ml)_ _,degased with argon . The mixture was heated to_ _80 °C_ _ for 2 hrs *_ |
Here is a chemical reaction formula: Reactants are aryl halide:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC(=C5)Cl)Cl)OC, amount is: 0.00020300000323913991 MOLE;amine:C1CCNC1, amount is: 0.00030399998649954796 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 1.52000002344721e-05 MOLE,Solvents are Solvent:COC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C, amount is: 1.52000002344721e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 5.070000042906031e-06 MOLE.Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC(=C5)N6CCCC6)Cl)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: _pyrrolidine (0.025 mL, 0.30 mmol)_ _was added to a suspension of_ _1-(4-(4-(5-chloro-4-(7-chloroimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)piperazin-1-yl)ethanone (104 mg, 0.20 mmol)_ _ in __dioxane (3.5 mL)_ _, followed by_ _sodium 2-methylpropan-2-olate (58.5 mg, 0.61 mmol)_ _, the mixture was degassed by bubbling N2 through , then a solution of pre-activated ( 50°C /15 min ) solution in dioxanne (1 ml) of __dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (7.26 mg, 0.02 mmol)_ _( Xphos) and_ _TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (4.65 mg, 5.07 µmol)_ _was added ._ _The brown-orange suspension was stirred at _ _105 °C_ _1 hr ( trace of reaction )_ _anisole (2 mL)_ _was added and then overnight under nitrogen atmosphere : few of reaction observed from 1 hr to 16 hrs heating_ _and TBAC ( 25 mg ) were added and the heating was continued overnight no reaction _ _ _ |
Here is a chemical reaction formula: Reactants are aryl halide:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC(=C5)Cl)Cl)OC, amount is: 0.00020300000323913991 MOLE;amine:C1CCNC1, amount is: 0.0010100000072270632 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0006089999806135893 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.090000169933774e-06 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.0399999104702147e-06 MOLE.Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)C4=CN=C5N4C=CC(=C5)N6CCCC6)Cl)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: _pyrrolidine (0.019 mL, 0.22 mmol)_ _was added to a suspension of_ _1-(4-(4-(5-chloro-4-(7-chloroimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)piperazin-1-yl)ethanone (104 mg, 0.20 mmol)_ _ in __dioxane (3.5 mL)_ _, followed by_ _sodium 2-methylpropan-2-olate (58.5 mg, 0.61 mmol)_ _, the mixture was degassed by bubbling N2 through , then __2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (3.79 mg, 6.09 µmol)_ _and_ _TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (2.79 mg, 3.04 µmol)_ _were added ._ _The orange suspension was stirred at _ _95 °C_ _for 2 hours under nitrogen atmosphere : no reaction observed_ _The same quantities of Binap and Pd2dba3 were added : 2 hours later ( no reaction ), _ _pyrrolidine (0.085 mL, 1.01 mmol)_ _was added and the yellow orange mixture was heated at 100°C overnight....no reaction_ _Water ( 1ml) was added , solution, and the heating was continued : mass pick 548, 549 appeared ( trce ? under SM pick ,Uplc, lcms2 acid conditions , trace of product) _ _An activated batch of Xantphos /Pd2dba3 ( 1.5/1 Pd ) was prepared and added and the heating continued no evolution_ _Not progressed isolation/recovery later_ _ _ _ _ |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=C(N=CN=C1Cl)OC2CCN(CC2)C(=O)OC(C)C, amount is: 0.03350000083446503 MOLE;amine:CC1=C(C=CC(=N1)S(=O)(=O)C)N, amount is: 0.03180000185966492 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.08030000329017639 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)CN1CCN2CCN(P1N(CC2)CC(C)C)CC(C)C, amount is: 0.0006689999718219042 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0003349999897181988 MOLE.Products are 0:CC1=C(N=CN=C1OC2CCN(CC2)C(=O)OC(C)C)NC3=C(N=C(C=C3)S(=O)(=O)C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Sodium tert-butoxide (9.83 mL, 80.31 mmol) was added portionwise to isopropyl 4-(6-chloro-5-methylpyrimidin-4-yloxy)piperidine-1-carboxylate (10.50 g, 33.46 mmol) and 2-methyl-6-(methylsulfonyl)pyridin-3-amine (5.92 g, 31.79 mmol) in dioxane (160 mL) at 18ºC over a period of 1 minute under nitrogen. The reaction was degassed with vacuum / nitrogen (6 times) and 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo{3.3.3}undecane (0.238 mL, 0.67 mmol) and Palladium(II) acetate (0.075 g, 0.33 mmol) was added and the suspension was stirred at 90 °C for a further 2 hours. More 2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo{3.3.3}undecane (0.238 mL, 0.67 mmol) and Palladium(II) acetate (0.075 g, 0.33 mmol) was added and the suspension was stirred at 90 °C for a further another 2 hours before being allowed to cool and stirred at room temperature overnight. The reaction was worked up with water (50 mL) and diluted with EtOAc (400 mL), and washed sequentially with water (100 mL) and saturated brine (50 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography (330g column), elution gradient 0 to 50% EtOAc in DCM (rising quickly to 20% then more slowly to 50%). The impure fractions were collected and combined and purified again in exactly the same way. Pure fractions were evaporated to dryness to afford isopropyl 4-(5-methyl-6-(2-methyl-6-(methylsulfonyl)pyridin-3-ylamino)pyrimidin-4-yloxy)piperidine-1-carboxylate, EN02029-72-solid-1, as a yellow solid. This solid was recrystallised from MeOH (~ 50 mL) and the resultant solid filtered off and washed with cold MeOH (2 x 5 mL), Et2O (2 x 5 mL) then isohexane (2 x 5 mL). The solid, EN02029-72-solid-2 was combined with the product from EN02029-67-01 and the whole sample was named EN02029-72-01 (8.39 g) and submitted to the collection. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C=NC=C1Br)N, amount is: 0.0009250000002793968 MOLE;amine:C1COCCN1, amount is: 0.004619999788701534 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0018500000005587935 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00011100000119768083 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.249999857274815e-05 MOLE.Products are 0:C1COCCN1C2=CN=CC(=C2)N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (20.76 mg, 0.09 mmol) was added to 5-bromopyridin-3-amine (160 mg, 0.92 mmol), morpholine (0.403 mL, 4.62 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (64.2 mg, 0.11 mmol) and cesium carbonate (603 mg, 1.85 mmol) in dioxane (5 mL). The resulting solution was stirred at 150 °C in the microwave for 30 minutes. The major product was the dimer. Rection abandoned. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C=NC=C1Br)N, amount is: 0.0009250000002793968 MOLE;amine:C1COCCN1, amount is: 0.04619999974966049 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0018500000005587935 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00011100000119768083 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.249999857274815e-05 MOLE.Products are 0:C1COCCN1C2=CN=CC(=C2)N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (20.76 mg, 0.09 mmol) was added to 5-bromopyridin-3-amine (160 mg, 0.92 mmol), morpholine (4028 µl, 46.24 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (64.2 mg, 0.11 mmol) and cesium carbonate (603 mg, 1.85 mmol). The resulting suspension was stirred at 150 °C for 30 minutes in a microwave. Reaction very messy but some product is visible. Reaction abandoned. |
Here is a chemical reaction formula: Reactants are amine:CC1=CC(=NN1C(=O)OC(C)(C)C)N, amount is: 0.0006419999990612268 MOLE;aryl halide:CC(C1=C(C=C(C=N1)F)F)NC2=C(C(=NC(=N2)Cl)N3CCOCC3)F, amount is: 0.000534999999217689 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.001069999998435378 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 4.819999958272092e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.2100000680657104e-05 MOLE.Products are 0:CC1=CC(=NN1)NC2=NC(=C(C(=N2)N3CCOCC3)F)NC(C)C4=C(C=C(C=N4)F)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (27.9 mg, 0.05 mmol), 2-chloro-N-(1-(3,5-difluoropyridin-2-yl)ethyl)-5-fluoro-6-morpholinopyrimidin-4-amine (200 mg, 0.54 mmol), tert-butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate (127 mg, 0.64 mmol) and cesium carbonate (349 mg, 1.07 mmol) were added to dioxane (8 mL). The mixture was purged with nitrogen for 15 minutes. Pd2(dba)3 (29.4 mg, 0.03 mmol) was added and the mixture heated at 110 °C for 3h. No sign of any reaction. |
Here is a chemical reaction formula: Reactants are amine:C1CNCCN1, amount is: 0.07599999755620956 MOLE;aryl halide:C1=CC(=CN=C1)Br, amount is: 0.01269999984651804 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.01899999938905239 MOLE,Solvents are Solvent:CC1=CC=C(C=C1)C, amount is: 0.0 ,Catalysts are metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C, amount is: 0.0006329999887384474 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0002530000056140125 MOLE.Products are 0:C1CN(CCN1)C2=CN=CC=C2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a 100 ml RBF, 3-bromopyridine (1.220 mL, 12.66 mmol) was taken in xylenes (20 mL). To this was added tris(dibenzylideneacetone)dipalladium(0) (0.232 g, 0.25 mmol), tri-t-butylphosphine (10%wt in Hexane) (1.281 g, 0.63 mmol) and sodium tert-butoxide (1.825 g, 18.99 mmol). Then piperazine (6.54 g, 75.95 mmol) was added to RM and the RM was then heated at 130 °C for 5 hrs. The reaction was monitored by LCMS. It did not show formation of product. The RM was discarded. |
Here is a chemical reaction formula: Reactants are amine:CN1CCC(CC1)CN, amount is: 0.0008570000063627958 MOLE;aryl halide:C1=CC(=CC(=C1)OC(F)(F)F)C2=CN=C3N2N=C(C=C3)Cl.Cl, amount is: 0.0005709999823011458 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0022799998987466097 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4, amount is: 0.00017100000695791095 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 5.709999823011458e-05 MOLE.Products are 0:CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A 50 mL round bottom flask was charged with a magnetic stir bar, toluene (6.376 mL), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine hydrochloride (200 mg, 0.57 mmol), (1-methylpiperidin-4-yl)methanamine (110 mg, 0.86 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (67.4 mg, 0.17 mmol), Pd2dba3 (52.3 mg, 0.06 mmol), and sodium tert-butoxide (220 mg, 2.28 mmol). The mixture was degassed with argon, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 110 °C with stirring for 16 h. The mixture was cooled to rt, pre-absorbed onto silca gel (~ 20 g) and purified on silica gel (80 g) using MeOH/DCM (1:3) as eluent to afford the title compound ~ 90 % pure. This material was then dissolved in DMSO and purified via reverse phase HPLC water/MECN (5->55%, 12 min) as eluent. The pure fractions were collected and converted to the corresponding HCl salt to afford N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (125 mg, 49.5 %) hydrochloride as a white solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)COC2=NC(=CC=C2)Br, amount is: 0.009999999776482582 MOLE;amine:C1COCCN1, amount is: 0.012000000104308128 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.014000000432133675 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0001500000071246177 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 9.999999747378752e-05 MOLE.Products are 0:C1COCCN1C2=NC(=CC=C2)OCC3=CC=CC=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Reagents split into 2 microwave tubes:- 2-(benzyloxy)-6-bromopyridine (2.641 g, 10.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.092 g, 0.10 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.093 g, 0.15 mmol) ,morpholine (1.045 g, 12.00 mmol) and sodium t-butoxide (1.345 g, 14.00 mmol) were suspended in toluene (30 mL). Degassed with N2 for 5 mins and sealed into a microwave tube. The reaction was heated to 120 °C for 10 minutes in the microwave reactor and cooled to RT. **_Work-up*_** The mixture was diluted with EtOAc and filtered through a short celite pad. The solution was then concentrated to dryness to give an orange viscous liquid (~4.7g). The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 4-(6-(benzyloxy)pyridin-2-yl)morpholine (2.350 g, 87 %) as a yellow oil. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.0004659999976865947 MOLE;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, amount is: 0.0003100000030826777 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0004659999976865947 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.209999992279336e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.099999958067201e-05 MOLE.Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)NC4=CC=NN4C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.31 mmol), 1-methyl-1H-pyrazol-5-amine (60.3 mg, 0.62 mmol), sodium 2-methylpropan-2-olate (44.7 mg, 0.47 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (38.7 mg, 0.06 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (28.4 mg, 0.03 mmol) were suspended in dioxane (2 mL) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 150 °C over a period of 30 minutes in the microwave reactor. Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 1% acetic acid) and acetonitrile as eluent. The fractions containing product were combined and basified with saturated aqueous solution of NaHCO3. Aqueous layer was extracted with CH2Cl2 (2x15 mL). Organic layer was washed with brine, dried over MgSO4 and concentrated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (57.0 mg, 48.0 %) as a yellow crystalline solid. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.0004659999976865947 MOLE;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, amount is: 0.0003100000030826777 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0004659999976865947 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 6.209999992279336e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.099999958067201e-05 MOLE.Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)NC4=CC=NN4C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.31 mmol), 1-methyl-1H-pyrazol-5-amine (60.3 mg, 0.62 mmol), sodium 2-methylpropan-2-olate (44.7 mg, 0.47 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (35.9 mg, 0.06 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (28.4 mg, 0.03 mmol) were suspended in dioxane (2 mL) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 150 °C over a period of 30 minutes in the microwave reactor. Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 1% acetic acid) and acetonitrile as eluent. The fractions containing product were combined and basified with saturated aqueous solution of NaHCO3. Aqueous layer was extracted with CH2Cl2 (2x15 mL). Organic layer was washed with brine, dried over MgSO4 and concentrated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (52.0 mg, 43.8 %) as a pale purple crystalline solid. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.0004659999976865947 MOLE;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, amount is: 0.0003100000030826777 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0004659999976865947 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.209999992279336e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.099999958067201e-05 MOLE.Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)NC4=CC=NN4C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.31 mmol), 1-methyl-1H-pyrazol-5-amine (60.3 mg, 0.62 mmol), sodium 2-methylpropan-2-olate (44.7 mg, 0.47 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (38.7 mg, 0.06 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (28.4 mg, 0.03 mmol) were suspended in dioxane (2 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 1 hour. Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (32.0 mg, 26.9 %) as a white solid. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.0004659999976865947 MOLE;aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, amount is: 0.0003100000030826777 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0004659999976865947 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.209999992279336e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 3.099999958067201e-05 MOLE.Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)NC4=CC=NN4C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.31 mmol), 1-methyl-1H-pyrazol-5-amine (60.3 mg, 0.62 mmol), sodium 2-methylpropan-2-olate (44.7 mg, 0.47 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (38.7 mg, 0.06 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (28.4 mg, 0.03 mmol) were suspended in dioxane (2 mL) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 140 °C for 5 minutes in the microwave reactor. Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (36.0 mg, 30.3 %) as an off-white solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)Cl, amount is: 0.0003100000030826777 MOLE;amine:CN1C(=CC=N1)N, amount is: 0.0006210000137798488 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00037200000951997936 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 4.9700000090524554e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.479999966453761e-05 MOLE.Products are 0:CN1CCC2=C(C1=O)C(=CC=C2)NC3=CC(=NC=C3Cl)NC4=CC=NN4C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.31 mmol), 1-methyl-1H-pyrazol-5-amine (60.3 mg, 0.62 mmol), cesium carbonate (121 mg, 0.37 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.7 mg, 0.05 mmol) and diacetoxypalladium (5.57 mg, 0.02 mmol) were suspended in dioxane (2 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 12 hours. Reaction was filtered, washed with CH2Cl2 and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (83 mg, 69.8 %) as a grey solid. Sample was combined with EN01622-31,32,33,35,36,37,38,39&40\. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (218 mg, EN01622-42-02) as a pale pink foam. |
Here is a chemical reaction formula: Reactants are aryl halide:C1COCCN1C2=CC(=O)N3C=CC=C(C3=N2)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.0017800000496208668 MOLE;amine:CC(C)(C)OC(=O)NC, amount is: 0.0035600000992417336 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.007120000198483467 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 8.900000102585182e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 4.450000051292591e-05 MOLE.Products are 0:CC(C)(C)OC(=O)N(C)C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CN5C4=NC(=CC5=O)N6CCOCC6, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: tert-butyl methylcarbamate (467 mg, 3.56 mmol) dissolved in dioxane (5ml) was added in one portion to 6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (1000 mg, 1.78 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (40.8 mg, 0.04 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (51.5 mg, 0.09 mmol) and cesium carbonate (2321 mg, 7.12 mmol) in dioxane (18mL) at 110 °C. The reaction flask was evacuated and blanketed with nitrogen 4X. The resulting suspension was stirred at 110 °C for 3 __ hours _. _ The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH/DCM (50/50) and pure fractions were evaporated to dryness to afford tert-butyl methyl(6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl)carbamate (771 mg, 80 %) as a yellow solid. Used crude in the next reaction see EN01985-94 |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)NC, amount is: 0.0035600000992417336 MOLE;aryl halide:C1COCCN1C2=CC(=O)N3C=CC=C(C3=N2)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.0017800000496208668 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.007120000198483467 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 8.900000102585182e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 4.450000051292591e-05 MOLE.Products are 0:CC(C)(C)OC(=O)N(C)C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CN5C4=NC(=CC5=O)N6CCOCC6, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: tert-butyl methylcarbamate (467 mg, 3.56 mmol) dissolved in dioxane (5ml) was added in one portion to 6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (1000 mg, 1.78 mmol) , TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (40.8 mg, 0.04 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (51.5 mg, 0.09 mmol) and cesium carbonate (2321 mg, 7.12 mmol) in degassed dioxane (18 mL), under nitrogen, at 110 °C. The reaction flask was evacuated and blanketed with nitrogen 4X. The resulting suspension was stirred at 110 °C for 3 __ hours with complete reaction observed by LCMS. After cooling, the mixture was partitioned between EtOAc (100mL) and water (50ml). The organics were separated and dried (MgSO4) and evaporated to give the crude product, tert- butyl methyl(6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl)carbamate (950 mg, 98 %) which was combined with the crude product from EN02472-66 and purified (proceedure detailed on that page). m/z (ES+) (M+H)+ = 543; HPLC tR= 2.91 min. |
Here is a chemical reaction formula: Reactants are aryl halide:C1COCCN1C2=CC(=O)N3C=CC=C(C3=N2)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.011599999852478504 MOLE;amine:CC(C)(C)OC(=O)NC, amount is: 0.02319999970495701 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.046300001442432404 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0005789999850094318 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00028899998869746923 MOLE.Products are 0:CC(C)(C)OC(=O)N(C)C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CN5C4=NC(=CC5=O)N6CCOCC6, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: tert-butyl methylcarbamate (3.04 g, 23.15 mmol) dissolved in dioxane (5ml) was added in one portion to 6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (6.50g, 11.58 mmol) , TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.265 g, 0.29 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.335 g, 0.58 mmol) and cesium carbonate (15.09 g, 46.30 mmol) in degassed dioxane (18 mL), under nitrogen. The reaction flask was evacuated and blanketed with nitrogen 4X. __The resulting suspension was stirred at 110 °C for 3 __ hours with complete reaction observed by LCMS. After cooling, the mixture was partitioned between EtOAc (500mL) and water (250ml). The organics were separated and dried (MgSO4) and evaporated to give the crude product which was combined with the crude product from EN02472-66. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford tert-butyl methyl(6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl)carbamate (5.61 g, 89 %) as a yellow solid. 1H NMR (400 MHz, CDCl3, 22°C) d 1.48 (9H, s), 3.34 - 3.39 (7H, m), 3.54 - 3.59 (4H, m), 5.63 (1H, s), 6.99 - 7.05 (1H, m), 7.34 (1H, dd), 7.56 (2H, m), 7.72 (1H, d), 7.86 (1H, dt), 8.04 (1H, s), 8.16 (1H, dt), 9.04 (1H, m). m/z (ES+) (M+H)+ = 543; HPLC tR= 2.89 min. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC2=NN=C(N2C=C1Br)C(F)(F)F, amount is: 0.0003760000108741224 MOLE;amine:COC1=CC(=CC=C1)OC2CCNCC2.Cl, amount is: 0.000450999999884516 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0013200000394135714 MOLE,Solvents are Solvent:CC1=CC=C(C=C1)C, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 2.8200000087963417e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 1.8799999452312477e-05 MOLE.Products are 0:COC1=CC(=CC=C1)OC2CCN(CC2)C3=CN4C(=NN=C4C(F)(F)F)C=C3, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 6-bromo-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (100 mg, 0.38 mmol), 4-(3-methoxyphenoxy)piperidine hydrochloride (110 mg, 0.45 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (17.56 mg, 0.03 mmol) and Sodium tert-butoxide (0.161 mL, 1.32 mmol) were suspended in xylenes (5 mL), then de-gassed and purged with nitrogen. Bis(dibenzylideneacetone)palladium (10.81 mg, 0.02 mmol) was added, and the mixture was sealed into a microwave tube. The reaction was heated to 100 °C for 20 minutes in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (25 mL), and washed with water (25 mL). The organic layer was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-(4-(3-methoxyphenoxy)piperidin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (45.0 mg, 30.5 %) as a white solid. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)CCOC2=CC=C(C=C2)C3CCNCC3, amount is: 0.00024399999529123306 MOLE;aryl halide:C1=CC2=NN=C(N2C=C1Br)C(F)(F)F, amount is: 0.00024399999529123306 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0004889999981969595 MOLE,Solvents are Solvent:CC1=CC=C(C=C1)C, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 1.82999992830446e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 1.2200000128359534e-05 MOLE.Products are 0:CN1C(=CC=N1)CCOC2=CC=C(C=C2)C3CCN(CC3)C4=CN5C(=NN=C5C(F)(F)F)C=C4, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 6-bromo-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (65 mg, 0.24 mmol), 4-(4-(2-(1-methyl-1H-pyrazol-5-yl)ethoxy)phenyl)piperidine (112 mg, 0.24 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (11.41 mg, 0.02 mmol) and Sodium tert-butoxide (0.060 mL, 0.49 mmol) were suspended in xylenes (5 mL), then de-gassed and purged with nitrogen. Bis(dibenzylideneacetone)palladium (7.02 mg, 0.01 mmol) was added, and the mixture was sealed into a microwave tube. The reaction was heated to 110 °C for 30 minutes in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (25 mL), and washed with water (25 mL). The aqueous layer was extraced with further EtOAc (25 mL). The combined organic layers were purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-(4-(4-(2-(1-methyl-1H-pyrazol-5-yl)ethoxy)phenyl)piperidin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (22.00 mg, 19.14 %) as a colourless gum. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=C(C=C1Cl)Cl)I, amount is: 0.04340000078082085 MOLE;amine:C1CNCCC1CO, amount is: 0.04340000078082085 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0013000000035390258 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.005210000090301037 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00043399998685345054 MOLE.Products are 0:C1CN(CCC1CO)C2=C(C=C(C=C2)Cl)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: **_Procedure:_** To a flask was added 1,3-Dichloro-4-iodobenzene (5.89 mL, 43.41 mmol), piperidin-4-ylmethanol (5 g, 43.41 mmol), cesium carbonate (28.3 g, 86.83 mmol), 18-Crown-6 (1.377 g, 5.21 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.811 g, 1.30 mmol), and toluene (50 mL). The mixture was stirred under nitrogen and Tris(dibenzylideneacetone)dipalladium(0) (0.398 g, 0.43 mmol) was added in one portion. The resultant yellow mixture was heated with oil bath temperature set at 125°C for 3 hours. LCMS shows desired product as well as other impurities. The reaction was cooled to room temperature. Ethyl acetate (2 x 200 mL) was added and the resultant mixture was extracted with saturated aqueous sodium chloride (200 mL). The organics were collected and dried over sodium sulfate. Ethyl acetate (100 mL) and hexanes (100 mL) were added to the crude and insoluble material filltered off. The filtrate was concentrated and chromatographed on silica gel (divided into 3 40 gram silica gel columns). The columns were eluted with hexanes up to ethyl acetate:hexanes (up to 100%). The desired product eluted between 40-60% ethyl acetate:hexanes. Clean fractions were combined from all columns and concentrated to give EN01972-36-1 (2.47 g, 21.87% yield) as an orange oil. |
Here is a chemical reaction formula: Reactants are amine:C1CNCCC1CO, amount is: 0.04340000078082085 MOLE;aryl halide:C1=CC(=C(C=C1Cl)Cl)I, amount is: 0.04340000078082085 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0013000000035390258 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.005210000090301037 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00043399998685345054 MOLE.Products are 0:C1CN(CCC1CO)C2=C(C=C(C=C2)Cl)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: **_Procedure:_** To a flask was added 1,3-Dichloro-4-iodobenzene (5.89 mL, 43.41 mmol), piperidin-4-ylmethanol (5 g, 43.41 mmol), cesium carbonate (28.3 g, 86.83 mmol), 18-Crown-6 (1.377 g, 5.21 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.811 g, 1.30 mmol), and toluene (50 mL). The mixture was stirred under nitrogen and Tris(dibenzylideneacetone)dipalladium(0) (0.398 g, 0.43 mmol) was added in one portion. The resultant yellow mixture was heated with oil bath temperature set at 125°C for 3 hours. LCMS shows desired product as well as other impurities. The reaction was cooled to room temperature. Ethyl acetate (2 x 200 mL) was added and the resultant mixture was extracted with saturated aqueous sodium chloride (200 mL). The organics were collected and dried over sodium sulfate. The crude was placed in the freezer for several days. The crude was dissolved in 10% methanol:dichloromethane (200 mL) and preabsorbed onto silica gel. Column chromatography was performed on silica gel eluting with hexanes up to ethyl acetate:hexanes (10%, 20%, 40%). Desired product eluted at 40% ethyl acetate:hexanes. Collected clean fractions and concentrated to give EN01972-57-1 (2.83 g, 25.06% yield) as an orange oil. Put aside product due to shift in priorities of project. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)I, amount is: 0.004900000058114529 MOLE;amine:CN(C)CCN, amount is: 0.009800000116229057 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009800000116229057 MOLE,Solvents are Solvent:CN(C)C=O, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0009800000116229057 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0004900000058114529 MOLE.Products are 0:CN(C)CCNC1=CC=CC=C1, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: In a 50 mL round-bottomed flask (t=g) was unsym-Dimethylethylenediamine (1.080 mL, 9.80 mmol), Iodobenzene (0.549 mL, 4.90 mmol), and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.449 g, 0.49 mmol)Cesium carbonate (2.396 g, 7.35 mmol) andCesium carbonate (2.396 g, 7.35 mmol) were added. in DMF (10 mL) ([VOLUME]) to give a brown suspension. Reaction stirred over night at 100°C. no reaction. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)NC1CNC1, amount is: 0.00038300000596791506 MOLE;aryl halide:COC1=NC=CC(=C1)Br, amount is: 0.00031900001340545714 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.000446999998530373 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 3.189999915775843e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 1.5999999959603883e-05 MOLE.Products are 0:CC(C)(C)OC(=O)NC1CN(C1)C2=CC(=NC=C2)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of all the reactants in toluene was heated in a sealed vial at 70 °C overnight. According to LC-MS the reaction was completed and the product had been formed. Toluene was removed, water was added and the product was extracted with DCM. The organic phase was dried through phase separator and concentrated. The crude was used without further purification in the next step, EN01762-02. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)NC1CNC1, amount is: 0.0012799999676644802 MOLE;aryl halide:COC1=NC=CC(=C1)Br, amount is: 0.0010600000387057662 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0014900000533089042 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00010599999950500205 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 5.32000012753997e-05 MOLE.Products are 0:CC(C)(C)OC(=O)NC1CN(C1)C2=CC(=NC=C2)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of all the reactants in toluene was heated in a sealed vial at 70 °C overnight. According to LC-MS the reaction was completed and the product had been formed. Toluene was removed, water was added and the product was extracted with DCM. The organic phase was dried through phase separator and concentrated. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.00013099999341648072 MOLE;amine:CN1CCC2=C(C1=O)C(=CC=C2)N, amount is: 0.00013099999341648072 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 1.3099999705445953e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.3099999705445953e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.539999958476983e-06 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC4=C3C(=O)N(CC4)C)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (23.06 mg, 0.13 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (50 mg, 0.13 mmol), diacetoxypalladium (1.469 mg, 6.54 µmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.57 mg, 0.01 mmol) and cesium carbonate (85 mg, 0.26 mmol) was stirred at 80 °C overnight under nitrogen. LCMS showed formation of more bis-arylation by-product than in _EN01775-08_ (DMA under micorwaves conditions). The crude was combined with EN01775-08-01 and poured onto a silicagel column. The crude product was purified by flash chromatography eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness to afford a gummy film in the flask **(37mg: not that bad)**. it was scratched in diethyl ether (soluble) then after Et2O evaporation in a few drops of MeCN. A solid crashed out. The resulting solid was taken up into diethyl ether, collected by filtration and dried to afford 8-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (19.00 mg, 33.7 %) as a white solid (a bit soluble in Et2O because some P1 remained in the Et2O filtrate). **not the real yield** |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.010499999858438969 MOLE;amine:CNC(=O)C1=CC=CC=C1N, amount is: 0.017799999564886093 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.020899999886751175 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0010499999625608325 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0005230000242590904 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.606 g, 1.05 mmol), diacetoxypalladium (0.118 g, 0.52 mmol), 2-amino-N-methylbenzamide (2.67 g, 17.80 mmol) and N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (4 g, 10.47 mmol) were dissolved in dioxane (120 mL) and argon was let to bubble in the mixture for 5 minutes.cesium carbonate (6.82 g, 20.94 mmol) was added and argon was let to bubble in the mixture for 5 minutes. The reaction was stirred at 90 °C for 2 hours. After taking 2 aliquotsd to check the reaction it turned from yello to grey. LCMS didn't show a complete clean reaction but it stopped. The reaction mixture was allowed to cool to room temperature under stirring, diluted with dichloromethane, insoluble was removed by filtration and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel (150g) eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness, giving a gummy foam. 60 mL of tBuOMe was added and the resulting solution was stirred at rt for 15 minutes. The resulting precipitate was collected by filtration, washed with tBuOMe and dried to a constant weight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (3.60 g, 85 %) as a pale beige solid. |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=CC=CC=C1N, amount is: 0.002240000059828162 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0013200000394135714 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0001320000010309741 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0001320000010309741 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.579999899258837e-05 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (76 mg, 0.13 mmol) and diacetoxypalladium (14.77 mg, 0.07 mmol) were dissolved in dioxane (15 mL) and argon was let to bubble in the mixture for 5 minutes. 2-amino-N- methylbenzamide (336 mg, 2.24 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (503 mg, 1.32 mmol) and cesium carbonate (858 mg, 2.63 mmol) were added and the reaction was heated to 90 °C, over a period of 90 minutes under nitrogen. LCMS didn't show a complete clean reaction (as Cs2CO3 got stuck on the flask). Vigourous stirring was applied and theaction was heated to 90 °C, over a period of 90 minutes under nitrogen. Crude LCMS was as expected. The reaction mixture was allowed to cool to room temperature under stirring, diluted with dichloromethane and decalite speed + was added. The mixture was concentrated and the crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness, giving a gummy foam of P1 (490mg). A bit of diethyl ether then a lot of pentane were added to obtain a solid, which was dried under vacuum at 50°C to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (450 mg, 77 %) as an yellow solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.00013099999341648072 MOLE;amine:CNC(=O)C1=CC=CC=C1N, amount is: 0.00026199998683296144 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 1.3099999705445953e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.3099999705445953e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 6.539999958476983e-06 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-amino-N-methylbenzamide (39.3 mg, 0.26 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (50 mg, 0.13 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.57 mg, 0.01 mmol), diacetoxypalladium (1.469 mg, 6.54 µmol) and cesium carbonate (85 mg, 0.26 mmol) were dissolved in dioxane (1 mL) and sealed into a microwave tube. Argon was let to bubble in the mixture for 5 minutes. The reaction was heated to 90 °C, over a period of 90 minutes. LCMS showed complete and pretty clean reaction. The reaction mixture was allowed to cool to room temperature under stirring, diluted with dichloromethane and decalite speed + was added. The mixture was concentrated and the crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness, a bit of diethyl ether was added in order to crystallised but it didn't work. So it was concentrated again to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (50.0 mg, 94 %) as a brown dry film. |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.05299999937415123 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.03530000150203705 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.003530000103637576 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.003530000103637576 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.001769999973475933 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of 2-amino-6-methoxy-N-methylbenzamide (9.55 g, 52.99 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (13.5 g, 35.33 mmol), diacetoxypalladium (0.397 g, 1.77 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.044 g, 3.53 mmol) and cesium carbonate (20.72 g, 63.59 mmol) in dioxane (150 mL) was degassed with argon, which was also let to bubble for 10 minutes then stirred at 100 °C overnight (yellow-ish dense suspension turning grey lighter). The reaction mixture was allowed to cool to rt, the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. (Insolubles~25g, which seemed to contain very little P1 by TLC and LCMS). The crude product (24.5g) was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate (pure AcOEt to remove by- product coming from overreaction). The solvent was evaporated to dryness to afford a foam (12.5g) which was dissolved in dichloromethane (100ml). The resulting crystalline precipitate was collected by filtration, washed with dichloromethane. The filtrate was concentrated down, taken up into DCM and a second crop was collected by filtration, which was combined with the first batch and dried to a constant weight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy- N-methylbenzamide (11.51 g, 75.0 %) as a white crystalline solid. The filtrate was concentrated to dryness, taken up into DCM and collected by filtration to give a second sample EN02972-35-02 (0.41 g, 0.944 mmol, 2.67 %). |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.10199999809265137 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.06800000369548798 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.006800000090152025 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.006800000090152025 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0034000000450760126 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred solution of N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (26 g, 68.04 mmol) and 2-amino-6-methoxy-N-methylbenzamide (18.39 g, 102.06 mmol) in dioxane (300 mL) is added cesium carbonate (39.9 g, 122.47 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.94 g, 6.80 mmol) and diacetoxypalladium (0.764 g, 3.40 mmol). Mixture was degassed 3 times with N2 and heated to 100°C overnight. LCMS crude seems OK. Reaction was cooled to room temperature then salts were filtered and the filtrate concentrated to afford a crude compound which was purified on silica, eluting with 5% MeOH in AcOEt. Solvent were evaporated to afford a gum which finished by crystallize in 100mL of CH2Cl2. Solid was filtered and dried to a constant weight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy- N-methylbenzamide (17.30 g, 58.5 %) as a white crystalline product. 1H NMR, purity check OK, 98% of purity. |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.0007849999819882214 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0003929999948013574 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 3.930000093532726e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 3.930000093532726e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.9600000086938962e-05 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of [Reactants], N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol), diacetoxypalladium (4.41 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (22.71 mg, 0.04 mmol) and cesium carbonate (256 mg, 0.79 mmol) in dioxane (2 mL) was degassed with argon then stirred at 100 °C for 2 hours sealed in a microwave vial. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford impure product EN01775-26-01. The impure product was repurified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1) - spillage occurred when collecting. The solvent was evaporated to dryness to afford 110mg of a foam, which was triturated in tBuOMe. The resulting precipitate was collected by filtration and dried to a constant weight to afford [Products] as a white solid EN01775-26-02 (81 mg, 0.186 mmol, 47.5 %). |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.00687999976798892 MOLE;amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.013799999840557575 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0006880000000819564 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0006880000000819564 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0003440000000409782 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of [Reactants], N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (2.63 g, 6.88 mmol), diacetoxypalladium (0.077 g, 0.34 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.398 g, 0.69 mmol) and cesium carbonate (4.48 g, 13.77 mmol) in dioxane (37 mL) was degassed with argon then stirred at 100 °C for 3 hours . The reaction mixture was concentrated to dryness, diluted with ethyl acetate (80 ml), washed with water (1 x 50 ml), brine, dried over magnesium sulfate and concentrated to afford an oil. The crude product was purified by flash chromatography on silica gel eluting with AcOet pure to remove impurities then 3 to 8% methanol in ethyl acetate. The solvent was evaporated to dryness to afford a foam which was dissolved in dichloromethane ( 12ml ). A solid was formed after a few minutes, which was filtered, dried .A white solid was obtained 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy- N-methylbenzamide (1.570 g, 52.5 %) |
Here is a chemical reaction formula: Reactants are amine:CN1CCOC2=CC=CC(=C2C1=O)N, amount is: 0.0007849999819882214 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0003929999948013574 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 3.930000093532726e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 3.930000093532726e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.9600000086938962e-05 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C4C(=CC=C3)OCCN(C4=O)C)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of 6-amino-4-methyl-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (151 mg, 0.79 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol), diacetoxypalladium (4.41 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (22.71 mg, 0.04 mmol) and cesium carbonate (256 mg, 0.79 mmol) in dioxane (2 mL) was degassed with argon then stirred at 100 °C for 2 hours sealed in a microwave vial. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford impure product EN01775-27-01. The impure product was repurified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness to afford 118mg of a sticky foam, which was triturated in a mixture of tBuOMe and pentane (~30-40% of tBuOMe). The mixture was concentrated down to get a light white foam, which could be handled. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=NC(=C1Br)Cl)Cl, amount is: 9.999999747378752e-05 MOLE;amine:C1=CC=C(C=C1)N, amount is: 0.00019999999494757503 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0001500000071246177 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 7.499999810534064e-06 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.499999936844688e-06 MOLE.Products are 0:C1=CC=C(C=C1)NC2=C(N=C(C=C2)Cl)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: BINAP (4.67 mg, 7.50 µmol) and Pd2dba3 (2.289 mg, 2.50 µmol) were dissolved in dioxane (1ml) and flushed with nitrogen. 3-bromo-2,6-dichloropyridine (0.023 g, 0.1 mmol), aniline (0.018 mL, 0.20 mmol) and sodium tert-butoxide (0.014 g, 0.15 mmol) were weight in another flask and flushed with nitrogen. The ligand- Pd mixture was subjoined and the reaction mixture was stirred at 100°C over night. Detection of the reaction was done by LC/MS. LC/MS showed the completion of the reation. the 3-bromo-2,6-dichloropyridine as well as the aniline were gone, but no desired product was detected. NMR verified the observations. The products have not been identified. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C=C(N=C1Cl)Cl)C(=O)O, amount is: 0.0005210000090301037 MOLE;amine:CC(C)(C)OC(=O)N, amount is: 0.0006249999860301614 MOLE,Reagents are Base:[O-]P(=O)([O-])[O-].[K+].[K+].[K+], amount is: 2.5999999706982635e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 2.5999999706982635e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.5999999706982635e-05 MOLE.Products are 0:CC(C)(C)OC(=O)NC1=NC(=CC(=C1)C(=O)O)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Reagents were mixed in a 25 mL round bottom flask and flushed well with nitrogen - heated at 100 °C for 16 h. The mixture looked dark black. Could not detect any starting material or product! It was discarded. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.0013500000350177288 MOLE;amine:CN1C(=CC=N1)N, amount is: 0.0016199999954551458 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0027000000700354576 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0002699999895412475 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.00013499999477062374 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (124 mg, 0.14 mmol) was added in one portion to 2,4-dichloropyridine (200 mg, 1.35 mmol), 1-methyl-1H-pyrazol-5-amine (158 mg, 1.62 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (156 mg, 0.27 mmol), and cesium carbonate (881 mg, 2.70 mmol) in 1,4-dioxane (20 mL) under nitrogen. The resulting mixture was stirred at 105°C for 2 hours. The reaction mixture was evaporated to dryness and redissolved in DCM (50 mL), and washed with water (50 mL). The organic layer was filtered using phase separating paper and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (66.0 mg, 23.41 %) as a yellow oil which solidified on standing. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.0006760000251233578 MOLE;amine:CN1C(=CC=N1)N, amount is: 0.0007430000114254653 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 7.970000297063962e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 7.970000297063962e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.7399999453336932e-05 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2,4-dichloropyridine (100mg, 0.68 mmol), 1-methyl-1H-pyrazol-5-amine (72.2 mg, 0.74 mmol) and cesium carbonate (330 mg, 1.01 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (46.1 mg, 0.08 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (25.06 mg, 0.03 mmol) were suspended in 1,4-dioxane (5 mL) and sealed into a microwave tube. The reaction was heated to 200°C for 1 hour in the microwave reactor and cooled to RT. The reaction mixture was evaporated to dryness and redissolved in DCM (20 mL), and washed with water (20 mL). The organic layer was filtered with phase separating paper and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (14.00 mg, 9.93 %) as a yellow oil which solidified on standing. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.007430000230669975 MOLE;aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.00675999978557229 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.010099999606609344 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0007970000151544809 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0002739999908953905 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (251 mg, 0.27 mmol) was [AP-added] to 2,4-dichloropyridine (1000mg, 6.76 mmol), 1-methyl-1H-pyrazol-5-amine (722 mg, 7.43 mmol), cesium carbonate (3302 mg, 10.14 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (461 mg, 0.80 mmol) in 1,4-dioxane (75 mL) warmed to 105ºC over a period of 21 hours under nitrogen. The reaction mixture was evaporated to dryness and redissolved in DCM (50 mL), and sequentially with water (25 mL). The organic layer was filtered using phase separating paper and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (710 mg, 50.4 %) as a brown oil. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.010099999606609344 MOLE;aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.00675999978557229 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.010099999606609344 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0007970000151544809 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0002739999908953905 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (251 mg, 0.27 mmol) was added in one portion to 2,4-dichloropyridine (1000mg, 6.76 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (826 mg, 7.43 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (461 mg, 0.80 mmol) and sodium tert-butoxide (974 mg, 10.14 mmol) in 1,4-dioxane (60 mL) warmed to 130ºC over a period of 10 minutes under nitrogen. The resulting mixture was stirred at 130°C for 20 hours. The reaction mixture was evaporated to dryness and redissolved in DCM (150 mL). Solids were filtered off by suction and the filtrate subsequently washed with water (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 4% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (802 mg, 56.9 %) as a yellow oil which crystallised on standing. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.10100000351667404 MOLE;aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.06759999692440033 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.10100000351667404 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.004050000105053186 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0013500000350177288 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (1.238 g, 1.35 mmol) was added in one portion to 2,4-dichloropyridine (10g, 67.57 mmol), 1-methyl-1H-pyrazol-5-amine (7.22 g, 74.33 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.346 g, 4.05 mmol) and sodium tert-butoxide (9.74 g, 101.36 mmol) in 1,4-dioxane (500 mL) warmed to 130ºC over a period of 10 minutes under nitrogen. The resulting mixture was stirred at 130 °C for 24 hours. The reaction mixture was evaporated to dryness and redissolved in DCM (300 mL), and washed with water (125 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 4% MeOH in DCM. Pure fractions were evaporated to dryness to afford EN01861-14-01 (2.93 g, 20.8 %) as a yellow crystalline solid. EN01861-14-01 (2.93 g) was combined with EN01861-09-01 (2.63g) to give EN01861-14-02 (5.56 g) as a yellow crystalline solid. |
Here is a chemical reaction formula: Reactants are amine:CN1C(=CC=N1)N, amount is: 0.0014900000533089042 MOLE;aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.0013500000350177288 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.00203000009059906 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00015999999595806003 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 5.4700001783203334e-05 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (50.1 mg, 0.05 mmol) was added in one portion to 2,4-dichloropyridine (200 mg, 1.35 mmol), 1-methyl-1H-pyrazol-5-amine (144 mg, 1.49 mmol), cesium carbonate (660 mg, 2.03 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (93 mg, 0.16 mmol) in 1,4-dioxane (20 mL) warmed to 105°C over a period of 24 hours under nitrogen. The reaction mixture was evaporated to dryness and redissolved in DCM (20 mL), and washed with water (25 mL). The organic layer filtered using phase separating paper and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (171 mg, 60.5 %) as a yellow crystalline solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN=C(C=C1Cl)Cl, amount is: 0.06759999692440033 MOLE;amine:CN1C(=CC=N1)N, amount is: 0.07429999858140945 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.10100000351667404 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.004050000105053186 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0013500000350177288 MOLE.Products are 0:CN1C(=CC=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (1.238 g, 1.35 mmol) was added in one portion to 2,4-dichloropyridine (10g, 67.57 mmol), 1-methyl-1H-pyrazol-5-amine (7.22 g, 74.33 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.346 g, 4.05 mmol) and cesium carbonate (33.0 g, 101.36 mmol) in 1,4-dioxane (350 mL) warmed to 105ºC over a period of 20 hours under nitrogen. The reaction mixture was evaporated to dryness and redissolved in DCM (250 mL), and washed with water (200 mL) The organic layer was filtered using phase separating paper and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Relavent fractions were repurified by flash silica chromatography, elution gradient 0 to 5% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford 4-chloro-N-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine (2.91 g, 20.66 %) as a yellow crystalline solid. |
Here is a chemical reaction formula: Reactants are amine:C1=CC=C(C=C1)N, amount is: 0.00011999999696854502 MOLE;aryl halide:C1=CC(=NC(=C1I)Cl)Cl, amount is: 9.999999747378752e-05 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 3.999999989900971e-06 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 3.999999989900971e-06 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.999999989900971e-06 MOLE.Products are 0:C1=CC=C(C=C1)NC2=C(N=C(C=C2)Cl)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The reaction vessel was charged with nitrogen, BINAP (2.491 mg, 4.00 µmol) and diacetoxypalladium (0.898 mg, 4.00 µmol) were dilutet in toluene (2 ml) and flushed with nitrogen.2,6-dichloro-3-iodopyridine (0.027 g, 0.1 mmol), aniline (10.96 µl, 0.12 mmol) and cesium carbonate (0.163 g, 0.50 mmol) were weight in another flask and flushed with nitrogen. The Pd-BINAP mixture was subjoined and the reaction mixture was warmed to 120° C and stirred over night. The reaction was monitored using LC/MS. No product could be obtained. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=NC(=C1I)Cl)Cl, amount is: 9.999999747378752e-05 MOLE;amine:C1=CC=C(C=C1)N, amount is: 0.00011999999696854502 MOLE,Reagents are Base:C(=O)([O-])[O-].[K+].[K+], amount is: 7.999999979801942e-06 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4, amount is: 7.999999979801942e-06 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.999999989900971e-06 MOLE.Products are 0:C1=CC=C(C=C1)NC2=C(N=C(C=C2)Cl)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: Biphenyl-2-yldicyclohexylphosphine (2.80 mg, 8.00 µmol) and diacetoxypalladium (0.898 mg, 4.00 µmol) were dilutet in dioxane (1 ml) and flushed with nitrogen. 2,6-dichloro-3-iodopyridine (0.027 g, 0.1 mmol), aniline (10.96 µl, 0.12 mmol) and potassium carbonate (0.276 g, 2.00 mmol) were weight in another flask and flushed with nitrogen. The ligand-Pd mixture was subjoined and the reaction mixture was stirred at 120°C over night. The reaction was monitored by LC/MS and TLC. No desired product could be obtained and the starting material was left. |
Here is a chemical reaction formula: Reactants are amine:C1=CC=C(C=C1)N, amount is: 0.004999999888241291 MOLE;aryl halide:C1=CC(=NC(=C1I)Cl)Cl, amount is: 0.0010000000474974513 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.001500000013038516 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 7.500000356230885e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 2.499999936844688e-05 MOLE.Products are 0:C1=CC=C(C=C1)NC2=C(N=C(C=C2)Cl)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The reaction was carried out under nitrogen. Two runs using the same amount of starting material (2,6-dichloro-3-iodopyridine (274 mg, 1 mmol)) and the same conditions were started and carried out as described in the following. BINAP (46.7 mg, 0.08 mmol) and Pd2(dba)3 (22.89 mg, 0.03 mmol) were given into a nitrogen charged reaction vessel and dissolved in dioxane (10ml). 2,6-dichloro-3-iodopyridine (274 mg, 1 mmol), aniline (0.457 ml, 5.00 mmol) and sodium tert-butoxide (144 mg, 1.50 mmol) were weight in another flask and flushed with nitrogen. The prepared ligand-Pd mixture was added and the reaction mixture was heated at 100°C over night. The reaction was monitored using TLC and LC/MS. After the reaction was completed, the dioxane was evapurated and both reaction vessels containing the same reaction-mixture were combined. The crude was solved in DCM, filtered through a silica plug and it followed a water work up using sodium bicarbonate (5 %), brine and water. The organic phase was dried over sodium sulfate and concentrated to yield a dark brown oil. NMR showed the desired product, as well as the bis-addition of aniline. The crude product was purified by reverse-phase preparative HPLC. Column: Kromasil C8. Eluent: A: MeCN, B: H2O/MeCN/CH3COOH, 95/5/0.2. Gradient: The A fraction was increased from 30 % to 70 % over 40 minutes. Flow: 70 mL/min. The relevant fractions (6-9) were concentrated and freeze dried to yield 220.3 mg (46%) a brown oil. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)NC1CCNCC1, amount is: 0.004999999888241291 MOLE;aryl halide:COC(=O)C1=CC(=CC=C1)Br, amount is: 0.004999999888241291 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.007000000216066837 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0005000000237487257 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0005000000237487257 MOLE.Products are 0:CC(C)(C)OC(=O)NC1CCN(CC1)C2=CC=CC(=C2)C(=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: All chemicals were mixed in a 50 mL round bottom flask. The solids were degassed and placed under nitrogen. Toluene was added and the mixture was stirred at 100°C for 24 h. Cooled and filtered. The filtrate was concentrated under vacuum. Crude product was mainly starting material but some product had been formed. The product was purified by silica gel chromatography using 1-4% methanol/DCM. Product was slightly more polar than starting material bromide. There was obtained 230 mg of the desired product as a solid. HNMR and LC MS ok. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)N, amount is: 0.012000000104308128 MOLE;aryl halide:C1=CN=C(C=C1F)Cl, amount is: 0.01140000019222498 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009120000177063048 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0009120000177063048 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0004560000088531524 MOLE.Products are 0:C1=CN=C(C=C1F)N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-chloro-4-fluoropyridine (1.5 g, 11.40 mmol), tert-butyl carbamate (1.403 g, 11.97 mmol), CESIUM CARBONATE (7.43 g, 22.81 mmol) ,TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.418 g, 0.46 mmol) and 9,9-DIMETHYL-4,5-BIS(DIPHENYLPHOSPHINO)XANTHENE (0.528 g, 0.91 mmol) were suspended in 1,4-dioxane (28 ml) ,degased with argon and heated to 90 °C for 4 hours. After cooling the reaction was quenched with water and extracted with ethyl acetate ( x 2 ). The combined organic phases were washed with water , a saturated aqueous solution of brine , dried over magnesium sulfate , concentrated then purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The product was diluted in DCM (5 mL) and was added TFA (1.00 mL). After 15 minutes, the volatiles were evaporated. The residue was treated with aq NH3 30% and reevaporated. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CN2C(=CN=C2C(=C1)F)C3=NC(=NC=C3Cl)Cl, amount is: 0.0009960000170394778 MOLE;amine:CC(C)(C)OC(=O)CN(C)C1=CC(=C(C=C1)N)OC, amount is: 0.0010999999940395355 MOLE,Reagents are Base:[O-]P(=O)([O-])[O-].[K+].[K+].[K+], amount is: 9.960000170394778e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 9.960000170394778e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 4.980000085197389e-05 MOLE.Products are 0:CC(C)(C)OC(=O)CN(C)C1=CC(=C(C=C1)NC2=NC=C(C(=N2)C3=CN=C4N3C=CC=C4F)Cl)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A microwave tube was charged with diacetoxypalladium (11.18 mg, 0.05 mmol), potassium phosphate (529 mg, 2.49 mmol),2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (62.0 mg, 0.10 mmol), 3-(2,5-dichloropyrimidin-4-yl)-8-fluoroimidazo[1,2-a]pyridine (282 mg, 1.00 mmol) purged with nitrogen. Dioxane (4.5 ml) was added followed by tert-butyl 2-((4-amino-3-methoxyphenyl)(methyl)amino)acetate (292 mg, 1.10 mmol). The resulting suspension was purged again and was heated at 100 °C for 1h30. After cooling, the mixture was filtered through a pad of Dicalite speed plus and washed with dichloromethane. The solvent were evaporated. PBO-01970-51-01 The crude product was purified by flash chromatography on silica gel (Merck cartridge SVF D26 - SI60 15-40µm - 30g) eluting with 0 up to 50% EtOAc in petroleum ether. Collected fractions were evaporated to afford tert-butyl 2-((4-(5-chloro-4-(8-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-ylamino)-3-methoxyphenyl)(methyl)amino)acetate (220 mg, 43.1 %) as a clear yellow solid. PBO-01970-51-02 |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.0026499999221414328 MOLE;aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I, amount is: 0.002570000011473894 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0030799999367445707 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00041099998634308577 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00020599999697878957 MOLE.Products are 0:CNC(=O)C1=C(C=CC=C1OC)NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (790 mg, 2.57 mmol), 2-amino-6-methoxy-N-methylbenzamide (477 mg, 2.65 mmol), diacetoxypalladium (46.2 mg, 0.21 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (238 mg, 0.41 mmol) and cesium carbonate (1005 mg, 3.08 mmol) were mixed together in dioxane (15 mL). Reaction was degassed with argon and was stirred at 90 °C overnight under argon. Reaction was filtered, washed with CH2Cl2 and filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (590 mg, 63.8 %) as a white foam. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I, amount is: 0.0013699999544769526 MOLE;amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.0013699999544769526 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0016400000313296914 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00021899999410379678 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00010900000052060932 MOLE.Products are 0:CNC(=O)C1=C(C=CC=C1OC)NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (420 mg, 1.37 mmol), 2-amino-6-methoxy-N-methylbenzamide (246 mg, 1.37 mmol), diacetoxypalladium (24.54 mg, 0.11 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (126 mg, 0.22 mmol) and cesium carbonate (534 mg, 1.64 mmol) were mixed together in dioxane (8 mL). Reaction was degassed with argon and was stirred at 90 °C overnight (15 hours) under argon. Reaction was filtered, washed with CH2Cl2 and the filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 10 to 30% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (325 mg, 66.1 %) as a white solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C(=CN=C1Cl)C(F)(F)F)I, amount is: 0.02280000038444996 MOLE;amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.023900000378489494 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.027300000190734863 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.003640000009909272 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.001820000004954636 MOLE.Products are 0:CNC(=O)C1=C(C=CC=C1OC)NC2=CC(=NC=C2C(F)(F)F)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (7 g, 22.77 mmol), 2-amino-6-methoxy-N-methylbenzamide (4.31 g, 23.91 mmol), diacetoxypalladium (0.409 g, 1.82 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.108 g, 3.64 mmol) and cesium carbonate (8.90 g, 27.32 mmol) were suspended in dioxane (75 ml). Argon was let to bubble into the dark purple blurred solution and the reaction mixture was heated to at 90 °C for 24h. (yellow suspension when temperature reached 70°C). The reaction mixture was allowed to cool to room temperature, diluted with DCM (some drop of MeOH) and filtered. Silica gel was added and solents were evaporated to afford the crude, which was purified twice* by flash chromatography on silica gel eluting with 10 to 60% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy-N-methylbenzamide (7.00 g, 85 %) as an yellow foam. |
Here is a chemical reaction formula: Reactants are amine:C1COCCN1, amount is: 0.003120000008493662 MOLE;aryl halide:CC(C)(C)OC(=O)NC1=CC(=CN=C1)I, amount is: 0.0006249999860301614 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0012499999720603228 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 7.500000356230885e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.1200001103570685e-05 MOLE.Products are 0:C1COCCN1C2=CN=CC(=C2)N, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: morpholine (0.272 mL, 3.12 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.07 mmol), tert-butyl 5-iodopyridin-3-ylcarbamate (200 mg, 0.62 mmol), diacetoxypalladium (7.01 mg, 0.03 mmol) and cesium carbonate (407 mg, 1.25 mmol) were suspended in 1,4-dioxane (4 mL) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford the boc protected product. HCl in dioxane (4M, 5mL) was added to the product . The resulting suspension was stirred at room temperature for 3 hours. The product was evaporated to dryness to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH plus 1% aqueous ammonia in DCM. Pure fractions were evaporated to dryness to afford 5-morpholinopyridin-3-amine (31.0 mg, 27.7 %) as a cream solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=C(C=C1CO)Br)F, amount is: 0.0007719999994151294 MOLE;amine:C1=CN=C(N=C1N)Cl, amount is: 0.0007719999994151294 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0015399999683722854 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 9.259999933419749e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.859999924316071e-05 MOLE.Products are 0:C1=CC(=C(C=C1CO)NC2=NC(=NC=C2)Cl)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (8.67 mg, 0.04 mmol) was added to 2-chloropyrimidin-4-amine (100 mg, 0.77 mmol), (3-bromo-4-fluorophenyl)methanol (158 mg, 0.77 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (53.6 mg, 0.09 mmol) and cesium carbonate (503 mg, 1.54 mmol) in 1,4-dioxane (4 mL) . The resulting suspension was stirred at 150 °C in the microwave for 30 minutes. None of the desired material was visible by LCMS. Reaction abandoned. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=CC=C(C=C1)Br, amount is: 0.0004689999914262444 MOLE;amine: CC(C)(C(=O)OC)N, amount is: 0.00042699999175965786 MOLE,Reagents are Base:CCC(C)(C)[O-].[Na+], amount is: 0.0004689999914262444 MOLE,Solvents are Solvent:C1=CC=C(C=C1)C(F)(F)F, amount is: 0.0 ,Catalysts are metal and ligand:CCCCP(C12CC3CC(C1)CC(C3)C2)C45CC6CC(C4)CC(C6)C5, amount is: 1.7099999240599573e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.1899999663000926e-05 MOLE.Products are 0:CC(C)(C(=O)OC)NC1=CC=C(C=C1)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 1-bromo-4-methoxybenzene (0.060 mL, 0.47 mmol), methyl 2-amino-2-methylpropanoate (0.05 g, 0.43 mmol), sodium 2-methylbutan-2-olate (0.052 g, 0.47 mmol), diacetoxypalladium (2.68 mg, 0.01 mmol) and methyl 2-(4-methoxyphenylamino)-2-methylpropanoate (0.00 µg) was added to a microwave vial. (TRIFLUOROMETHYL)-BENZENE (0.5 mL) was used as solvent (1-1.2 mL/mmol amine). The mixture was heated in microwave at 180° for 60min. No conversion of startingmaterial was observed. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC(=CC=C1C(F)(F)F)Cl, amount is: 0.0005119999987073243 MOLE;amine: CC(C)(C(=O)OC)N, amount is: 0.00042699999175965786 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0008539999835193157 MOLE,Solvents are Solvent:C1=CC=C(C=C1)C(F)(F)F, amount is: 0.0 ,Catalysts are metal and ligand:CCCCP(C12CC3CC(C1)CC(C3)C2)C45CC6CC(C4)CC(C6)C5, amount is: 4.270000135875307e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.1300000298651867e-05 MOLE.Products are 0:CC(C)(C(=O)OC)NC1=CC=C(C=C1)C(F)(F)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 1-chloro-4-(trifluoromethyl)benzene (0.068 mL, 0.51 mmol), methyl 2-amino-2-methylpropanoate (0.05 g, 0.43 mmol),BUTYLDI-1-ADAMANTYLPHOSPHINE (0.015 g, 0.04 mmol), sodium 2-methylpropan-2-olate (0.082 g, 0.85 mmol) and diacetoxypalladium (4.79 mg, 0.02 mmol) was added to a microwave vial. (TRIFLUOROMETHYL)-BENZENE (0.5 mL) was used as solvent, before use the solvent was bubbled with nitrogen (1-1.2 mL/mmol amine). The mixture was bubbled with nitrogen before the vial was sealed. The mixture was heated in microwave at 180° for 60min.. The mixture was heated in microwave at 180° for 60min. No conversion of startingmaterial was observed. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=CC=C(C=C1)Cl, amount is: 0.0014199999859556556 MOLE;amine: CC(C)(C(=O)OC)N, amount is: 0.0017099999822676182 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0017099999822676182 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:CCCCP(C12CC3CC(C1)CC(C3)C2)C45CC6CC(C4)CC(C6)C5, amount is: 5.690000034519471e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.8500000553322025e-05 MOLE.Products are 0:CC1=CC=C(C=C1)NC(C)(C)C(=O)OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A flask was loaded with diacetoxypalladium (6.39 mg, 0.03 mmol), BUTYLDI-1-ADAMANTYLPHOSPHINE (0.020 g, 0.06 mmol), sodium 2-methylpropan-2-olate (0.164 g, 1.71 mmol) and methyl 2-amino-2-methylpropanoate (0.2 g, 1.71 mmol). The flask was evacuated and backfilled and toluene (5ml) and 1-chloro-4-methylbenzene (0.168 ml, 1.42 mmol) was added.The mixture was stirred for 20h at 120°. No conversion of startingmaterial was observed. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.01759999990463257 MOLE;aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.01600000075995922 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.024000000208616257 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0014400000218302011 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0009609999833628535 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (5 g, 16.02 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (2.453 g, 17.62 mmol) and cesium carbonate (7.83 g, 24.03 mmol) were suspended in 1,4-dioxane (75 mL). Nitrogen was bubbled through mixture for 15 minutes. (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.834 g, 1.44 mmol) and diacetoxypalladium (0.216 g, 0.96 mmol) were added and flask was purged with nitrogen (x3). Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 60 mL). Silica (63-200 µm) was added to the filtrate and mixture was concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 6% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (3.35 g, 50.4 %) as a dark green foam => _contains CH2Cl2 and MeOH._ EtOAc (10 mL) was added and mixture was stirred at room temperature for 5 hours. The resulting solid was filtered, washed with cold EtOAc and dried under high vacuum at 50°C overnight to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (2.41 g, 36.3 %) as a pale yellow solid => _crystalline powder under polarized light microscopy_ |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.1080000028014183 MOLE;aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.08969999849796295 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.13500000536441803 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.008070000447332859 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.005379999987781048 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: To a stirred solution of 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (28 g, 89.70 mmol) in 1,4-dioxane (300 mL) were added 1-isopropyl-3-methyl-1H-pyrazol-5-amine (14.98 g, 107.64 mmol), cesium carbonate (43.8 g, 134.55 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.67 g, 8.07 mmol) and diacetoxypalladium (1.208 g, 5.38 mmol) Mixture was degassed 3 times with N2 and heated to reflux overnight: OK. Reaction was cooled down, then filtered, salts were washed with 500mL of a 90/10 solution of CH2Cl2/MeOH and the filtrate was concentrated. Residue was then dissolved in CH2Cl2/MeOH, adsorbed on silica and purified by chromatography, eluting with 7% of MeOH in CH2Cl2. Solvent were concentrated and the solid obtained was stirred in 300mL of AcOEt for 3h. product was filtered, washed with AcOEt and dried on vacuum at 50°C for the we. 1H NMR indicates the presence of 7% of AcOEt... Need to dissolve the product in EtOH, then concentrated to dryness and stirred with 500mL of water for 3h. Solid was filtered, washed with water and dried on vacuum overnight at 50°C to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (21.50 g, 57.8 %) as a white powder. Purity-check OK. |
Here is a chemical reaction formula: Reactants are aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.0006409999914467335 MOLE;amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.0012799999676644802 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0009609999833628535 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.00012799999967683107 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 9.609999688109383e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (200 mg, 0.64 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (178 mg, 1.28 mmol) and sodium 2-methylpropan-2-olate (92 mg, 0.96 mmol) were suspended in 1,4-dioxane (3 mL). Nitrogen was bubbled through mixture for 10 minutes. (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (74.1 mg, 0.13 mmol) and BIS(DIBENZYLIDENEACETONE)PALLADIUM(0) (55.3 mg, 0.10 mmol) were added and tube was sealed. Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 10 mL) and concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (97 mg, 36.5 %) as a pink foam. |
Here is a chemical reaction formula: Reactants are aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.0006409999914467335 MOLE;amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.0012799999676644802 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0019199999514967203 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.410000059986487e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.199999991920777e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (200 mg, 0.64 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (178 mg, 1.28 mmol) and cesium carbonate (626 mg, 1.92 mmol) were suspended in 1,4-dioxane (3 mL). Nitrogen was bubbled through mixture for 10 minutes. 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (39.9 mg, 0.06 mmol) and diacetoxypalladium (7.19 mg, 0.03 mmol) were added and tube was sealed. Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 10 mL) and concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (125 mg, 47.0 %) as a pink foam => _contaminated by a few BINAP or BINAP by- products_ |
Here is a chemical reaction formula: Reactants are aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.0006409999914467335 MOLE;amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.0012799999676644802 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0019199999514967203 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00019200000679120421 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 9.609999688109383e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (200 mg, 0.64 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (178 mg, 1.28 mmol) and cesium carbonate (626 mg, 1.92 mmol) were suspended in 1,4-dioxane (3 mL). Nitrogen was bubbled through mixture for 10 minutes. 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (120 mg, 0.19 mmol) and diacetoxypalladium (21.58 mg, 0.10 mmol) were added and tube was sealed. Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 10 mL) and concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (98 mg, 36.9 %) as a pink foam => _impure, contains BINAP or BINAP by- products_ |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.0012799999676644802 MOLE;aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.0006409999914467335 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0009609999833628535 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 4.8099998821271583e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.199999991920777e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (200 mg, 0.64 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (178 mg, 1.28 mmol) and cesium carbonate (313 mg, 0.96 mmol) were suspended in 1,4-dioxane (3 mL). Nitrogen was bubbled through mixture for 10 minutes. (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (27.8 mg, 0.05 mmol) and diacetoxypalladium (7.19 mg, 0.03 mmol) were added and tube was sealed. Mixture was stirred at reflux overnight => _incomplete reaction_. Reaction was heated for a further 7 hours => _no evolution_. More Pd(OAc)2 and Xantphos were added, mixture was degassed with nitrogen and heated at reflux overnight => _complete_. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 10 mL) and concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (90 mg, 33.9 %) as a pink foam. |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.0007050000131130219 MOLE;aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.0006409999914467335 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0019199999514967203 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.410000059986487e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.199999991920777e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (200 mg, 0.64 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (98 mg, 0.70 mmol) and cesium carbonate (626 mg, 1.92 mmol) were suspended in 1,4-dioxane (3 mL). Nitrogen was bubbled through mixture for 10 minutes. 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (39.9 mg, 0.06 mmol) and diacetoxypalladium (7.19 mg, 0.03 mmol) were added and tube was sealed. Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 10 mL). Silica (63-200 µm) was added to the filtrate and mixture was concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (120 mg, 45.1 %) as a pale beige foam => _contaminated by a few BINAP or BINAP by-products_ |
Here is a chemical reaction formula: Reactants are aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.0006409999914467335 MOLE;amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.0009609999833628535 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0019199999514967203 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 6.410000059986487e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.199999991920777e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (200 mg, 0.64 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (134 mg, 0.96 mmol) and cesium carbonate (626 mg, 1.92 mmol) were suspended in 1,4-dioxane (3 mL). Nitrogen was bubbled through mixture for 10 minutes. 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (39.9 mg, 0.06 mmol) and diacetoxypalladium (7.19 mg, 0.03 mmol) were added and tube was sealed. Mixture was stirred at reflux overnight. Reaction was allowed to cool to room temperature, filtered, washed with CH2Cl2/MeOH (9/1, 10 mL). Silica (63-200 µm) was added to the filtrate and mixture was concentrated to dryness. The crude product was purified by flash chromatography (dry loading) on silica gel eluting with 1 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (127 mg, 47.8 %) as a pale beige foam => _contaminated by a few BINAP or BINAP by-products_ |
Here is a chemical reaction formula: Reactants are amine:CC1=NN(C(=C1)N)C(C)C, amount is: 0.000910000002477318 MOLE;aryl halide:CONC(=O)C1=CC=CC=C1NC2=CC(=NC=C2Cl)Cl, amount is: 0.000455000001238659 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0006820000126026571 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 9.100000170292333e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd], amount is: 6.820000271545723e-05 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: dioxane (4.3 mL) was added to 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (142 mg, 0.45 mmol), 1-isopropyl-3-methyl-1H-pyrazol-5-amine (127 mg, 0.91 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (52.6 mg, 0.09 mmol), BIS(DIBENZYLIDENEACETONE)PALLADIUM (39.2 mg, 0.07 mmol) and sodium 2-methylpropan-2-olate (65.6 mg, 0.68 mmol) and sealed into a microwave tube. The reaction was heated to 150 °C for 30 minutes in the microwave reactor and cooled to RT. Reaction mixture from EN04231/5 was combined and filtered through a PTFE cup to remove insoluble precipitate, washed filter with dioxane and combined filtrates were purified by ion exchange chromatography, using an 25g SCX-2 column. The desired product was eluted from the column using 7M NH3/MeOH and product fractions were evaporated to dryness to afford crude product (457 mg). The crude product was purified by flash silica (40g grace) chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford 2-(5-chloro-2-(1-isopropyl-3-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-N-methoxybenzamide (175 mg, 93 %) as a beige solid. |
Here is a chemical reaction formula: Reactants are amine:C1=C(N=C(C=N1)Cl)N, amount is: 0.07909999787807465 MOLE;aryl halide:CS(=O)(=O)C1=CC=C(C=C1)Br, amount is: 0.07909999787807465 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.004749999847263098 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.004749999847263098 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.002369999885559082 MOLE.Products are 0:CS(=O)(=O)C1=CC=C(C=C1)NC2=CN=CC(=N2)Cl, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 1-bromo-4-(methylsulfonyl)benzene (18.6 g, 79.12 mmol) then cesium carbonate (33.5 g, 102.85 mmol) were successively added to a solution of 6-chloropyrazin-2-amine (10.25 g, 79.12 mmol) in 1,4-dioxane (300 ml). The mixture was purged with nitrogen, then (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.75 g, 4.75 mmol) and diacetoxypalladium (0.533 g, 2.37 mmol) were added, the mixture was purged with nitrogen then heated to 85°C for 3 hours. After cooling the mixture was diluted with ethylacetate (300 mL), filtered, the solid washed with ethyl acetate (2x100 mL). Filtrate was washed with water (500 mL) => _emulsion, 100 mL of brine were added to help separation of layers._ Organics were washed with brine and dried over MgSO4. Crude product (28g) was purified by flash chromatography on silica gel (solid deposit) eluting with 1 to 4% methanolic ammonia (7 N) in dichloromethane => _no separation !! crude was flushed_. The solvent was evaporated to dryness to afford crude product (22g). It was recrystallised from EtOAc (~450 mL) to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (14.00 g, 62.4 %, EN03787-21-01) as a white crystalline solid => _purity = 91%, contains 6.9% EtOAc_. Silica (63-200 µm) was added to filtrate and it was concentrated to dryness to be purified by flash chromatography on silica gel eluting with 1 to 4% methanolic ammonia (7 N) in dichloromethane => _again, no separation !!_ Fractions containing product were combined and concentrated to dryness. Residue (4.3g) was recrystallised from EtOAc (~70 mL) to afford 6-chloro-N-(4-(methylsulfonyl)phenyl)pyrazin-2-amine (1.80 g, 8.0 %, EN03787-21-02) as a white crystalline solid => _purity = 91%, contains 6.5% EtOAc._ **_HMS03866_** |
Here is a chemical reaction formula: Reactants are aryl halide:CN1C=C(C(=N1)C(F)(F)F)N.Cl, amount is: 0.0006070000235922635 MOLE;amine:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)Cl, amount is: 0.00030300000798888505 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0007580000092275441 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 4.8499998229090124e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 2.429999949526973e-05 MOLE.Products are 0:CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)NC3=CN(N=C3C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylbenzamide (100 mg, 0.30 mmol), 1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-amine hydrochloride (122 mg, 0.61 mmol), cesium carbonate (247 mg, 0.76 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.1 mg, 0.05 mmol) and diacetoxypalladium (5.45 mg, 0.02 mmol) were suspended in dioxane (1.5 mL) and sealed into a tube. The reaction was degased, purged with nitrogen and heated to 100 °C for 18 hours. Reaction was filtered. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford N-methyl-2-(2-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)benzamide (84 mg, 60.4 %) as a yellow crystalline solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C=NC=C1Br)C(F)(F)F, amount is: 0.0004419999895617366 MOLE;amine:CN, amount is: 0.0008849999867379665 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0008849999867379665 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.3300000318849925e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C(Cl)(Cl)Cl.[Pd].[Pd], amount is: 8.850000085658394e-06 MOLE.Products are 0:CNC1=CN=CC(=C1)C(F)(F)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-bromo-5-(trifluoromethyl)pyridine (100 mg, 0.44 mmol), methylamine 2 M in THF (0.442 mL, 0.88 mmol), and cesium carbonate (202 mg, 0.62 mmol) were suspended in dioxane (3 mL) . The reaction was purged with nitrogen for 30 minutes then 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (7.68 mg, 0.01 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0)-CHLOROFORM ADDUCT (9.16 mg, 8.85 µmol) were added. The reaction was heated at 130 c for 30mins. No REACTION ABANDONED |
Here is a chemical reaction formula: Reactants are aryl halide:C1=C(C=NC=C1Br)C(F)(F)F, amount is: 0.0004419999895617366 MOLE;amine:CN.Cl, amount is: 0.0008849999867379665 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0008849999867379665 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.3300000318849925e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C(Cl)(Cl)Cl.[Pd].[Pd], amount is: 8.850000085658394e-06 MOLE.Products are 0:CNC1=CN=CC(=C1)C(F)(F)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 3-bromo-5-(trifluoromethyl)pyridine (100 mg, 0.44 mmol), methylamine hydrochloride (59.8 mg, 0.88 mmol), and cesium carbonate (490 mg, 1.50 mmol) were suspended in dioxane (3 mL) . The reaction was purged with nitrogen for 30 minutes then 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (7.68 mg, 0.01 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0)-CHLOROFORM ADDUCT (9.16 mg, 8.85 µmol) were added. The reaction was heated to 130 °C in a CEM microwave for 1 hour. No Product formed. Abandoned |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)N1CCNC(=O)C1, amount is: 0.0004990000161342323 MOLE;aryl halide:COC1=C(C=CC(=C1)Cl)[N+](=O)[O-], amount is: 0.0004990000161342323 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 2.9999999242136255e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 2.9999999242136255e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 1.9999999494757503e-05 MOLE.Products are 0:CC(C)(C)OC(=O)N1CCN(C(=O)C1)C2=CC(=C(C=C2)[N+](=O)[O-])OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of tert-butyl 3-oxopiperazine-1-carboxylate (100 mg, 0.50 mmol), 4-chloro-2-methoxy-1-nitrobenzene (94 mg, 0.50 mmol), cesium carbonate (244 mg, 0.75 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.34 mg, 0.03 mmol) and diacetoxypalladium (4.48 mg, 0.02 mmol) was dried for 15 min under HV. Degassed dioxane (1,0-1,2 ml) was added and the resulting mixture was stirred at 90°c for 16 hours under inert atmosphere. TLC showed consumption of both SM and new spot (UV active). Reaction combined with EN02378-08 (same TLC profile).LC-MS of crude: EN02378-07-01 Extraction: AE/2M Na2CO3 sol. Purification by chromatography: eluent AE/hexane 20/80 to 60/40. **Isolated: m= 240 mg** ; orange foam. FLA 02378-07-02: 1H NMR, LC-MS: OK. Estimated yield: 68%. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)N1CCNC(=O)C1, amount is: 0.00749000022187829 MOLE;aryl halide:COC1=C(C=CC(=C1)Cl)[N+](=O)[O-], amount is: 0.00749000022187829 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0003370000049471855 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0003370000049471855 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0001900000061141327 MOLE.Products are 0:CC(C)(C)OC(=O)N1CCN(C(=O)C1)C2=CC(=C(C=C2)[N+](=O)[O-])OC, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A mixture of tert-butyl 3-oxopiperazine-1-carboxylate (1500 mg, 7.49 mmol), 4-chloro-2-methoxy-1-nitrobenzene (1405 mg, 7.49 mmol),cesium carbonate (3417 mg, 10.49 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (195 mg, 0.34 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (174 mg, 0.19 mmol)was dried for 15 min under HV. Degassed dioxane (17 ml) was added and the resulting mixture was stirred at 90°C for 16 hours under inert atmosphere. Work-up and purification: see EN02378-07-02. tert-butyl 4-(3-methoxy-4-nitrophenyl)-3-oxopiperazine-1-carboxylate (2640 mg, 100 %) was isolated as an orange foam. FLA 02378-10-01: 1H NMR, LC-MS: OK. |
Here is a chemical reaction formula: Reactants are aryl halide:COCCOC1=CC(=CC(=C1)[N+](=O)[O-])I, amount is: 0.01209999993443489 MOLE;amine:C1COCCN1, amount is: 0.015699999406933784 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.015699999406933784 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.00036199999158270657 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0006040000007487833 MOLE.Products are 0:COCCOC1=CC(=CC(=C1)[N+](=O)[O-])N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (0.136 g, 0.60 mmol) was added to a stirred mixture of 1-iodo-3-(2-methoxyethoxy)-5-nitrobenzene (3.9 g, 12.07 mmol), morpholine (1.373 mL, 15.69 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.225 g, 0.36 mmol) and cesium carbonate (11.80 g, 36.21 mmol) dissolved in toluene (100 mL) over a period of 5 minutes, degased and under argon. The resulting mixture was heated at 110 °C for 4 hours.The toluene was evaporated , water ( 50ml) was added and the mixture was extracted with ethyle acetate, dried over MgSO4, filtered and asorbed on silica gel.The crude product was purified by flash chromatography on silica gel eluting with 1 to 4% methanol in dichloromethane. The solvent was evaporated to dryness to afford 4-(3-(2-methoxyethoxy)-5-nitrophenyl)morpholine (0.550 g, 16.14 %) as a orange solid. ( starting material unreacted : 2 .5g) |
Here is a chemical reaction formula: Reactants are aryl halide:COCCOC1=CC(=CC(=C1)[N+](=O)[O-])I, amount is: 0.007739999797195196 MOLE;amine:C1COCCN1, amount is: 0.010099999606609344 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.010099999606609344 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.0007740000146441162 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0003870000073220581 MOLE.Products are 0:COCCOC1=CC(=CC(=C1)[N+](=O)[O-])N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (0.087 g, 0.39 mmol) was added to a stirred mixture of 1-iodo-3-(2-methoxyethoxy)-5-nitrobenzene (2.5 g, 7.74 mmol), cesium carbonate (7.56 g, 23.21 mmol) and morpholine (0.880 mL, 10.06 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.482 g, 0.77 mmol) dissolved in toluene (80 mL) and dioxane (20 mL) over a period of 10 minutes, degased and under argon. The resulting suspension was heated at 110 °C for 15 hours.Solvents were evaporated and the mixture was adsorbed with ammonia/methanol 7N on silica gel.The crude product was purified by flash chromatography on silica gel eluting with 40 to 60% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford 4-(3-(2-methoxyethoxy)-5-nitrophenyl)morpholine (2.000 g, 92 %) as a orange solid. |
Here is a chemical reaction formula: Reactants are aryl halide:COCCOC1=CC(=CC(=C1)[N+](=O)[O-])I, amount is: 0.029999999329447746 MOLE;amine:C1COCCN1, amount is: 0.039000000804662704 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.09009999781847 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.003000000026077032 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.001500000013038516 MOLE.Products are 0:COCCOC1=CC(=CC(=C1)[N+](=O)[O-])N2CCOCC2, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: The diacetoxypalladium (0.337 g, 1.50 mmol) was added to a stirred mixture of 1-iodo-3-(2-methoxyethoxy)-5-nitrobenzene (9.7 g, 30.02 mmol), cesium carbonate (29.3 g, 90.07 mmol) and morpholine (3.41 mL, 39.03 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (1.869 g, 3.00 mmol) dissolved in toluene (200 mL) and dioxane (50 mL) The reaction was degased, purged with argon and heated at 110 °C for 15 hours. The mixture was diluted with dichloromethane (250ml) the salts were fitered, the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 15% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 4-(3-(2-methoxyethoxy)-5-nitrophenyl)morpholine (4.50 g, 53.1 %) as a orange solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.00036899998667649925 MOLE;amine:CC(C)(C)OC(=O)NC, amount is: 0.0014799999771639705 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0014799999771639705 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 1.8500000805943273e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 9.229999704984948e-06 MOLE.Products are 0:CC(C)(C)OC(=O)N(C)C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CC5=C4OC(=CC5=O)N6CCOCC6, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 6-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (207.4 mg, 0.37 mmol), tert-butyl methylcarbamate (194 mg, 1.48 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (10.69 mg, 0.02 mmol) and cesium carbonate (481 mg, 1.48 mmol) were suspended in dioxane (6 mL) and sealed into a microwave tube. The reaction was heated to 140 °C for 1 hour in the microwave reactor and cooled to RT. The reaction mixture was filtered then silica gel (2 g) added. The mixture was concentrated _in vacuo_ to yield a white powder which was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford tert-butyl methyl(6-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-2-yl)carbamate (70.0 mg, 34.9 %) as a white solid. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)NC, amount is: 0.0026000000070780516 MOLE;aryl halide:C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.0017300000181421638 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.006940000224858522 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 8.669999806443229e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 4.3399999412940815e-05 MOLE.Products are 0:CC(C)(C)OC(=O)N(C)C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CC5=C4OC(=CC5=O)N6CCOCC6, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of tert-butyl methylcarbamate (341 mg, 2.60 mmol) in dioxane (17.300 ml) was added to a stirred mixture of 6-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (974 mg, 1.73 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (39.7 mg, 0.04 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (50.2 mg, 0.09 mmol) and cesium carbonate (2261 mg, 6.94 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 18 hours. The reaction mixture was poured into water (100 mL) and EtOAc (100 mL). Methanol addition was required to aid separation of layers. **[would vac off dioxane in future]**. The aqueous was further extracted with EtOAc (2 x 50 mL) and DCM (50 mL), all with the aid of methanol for layer separation. The combined organics were washed with saturated brine solution (still formed emulsions), dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 4% 7M NH3/MeOH in DCM. Pure fractions were evaporated to dryness to afford tert-butyl methyl(6-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-2-yl)carbamate (630 mg, 66.9 %) as a yellow solid. This was taken through to the next step at 85% pure, with no further purification. |
Here is a chemical reaction formula: Reactants are amine:CC(C)(C)OC(=O)NC, amount is: 0.00026699999580159783 MOLE;aryl halide:C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.00017800000205170363 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0007120000082068145 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 8.89999955688836e-06 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 4.44999977844418e-06 MOLE.Products are 0:CC(C)(C)OC(=O)N(C)C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CC5=C4OC(=CC5=O)N6CCOCC6, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of tert-butyl methylcarbamate (35.0 mg, 0.27 mmol) in dioxane (1.781 ml) was added to a stirred mixture of 6-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (100 mg, 0.18 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (4.08 mg, 4.45 µmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.15 mg, 8.90 µmol) and cesium carbonate (232 mg, 0.71 mmol). The resulting mixture was stirred under nitrogen at 110 °C for 3 hours. The cooled reaction mixture was diluted with methanol and the residue was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford tert-butyl methyl(6-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-2-yl)carbamate (97 mg, 100 %) as a orange residue. 100% assumed and this was progressed to the next stage with no further purification. |
Here is a chemical reaction formula: Reactants are amine:CC(=O)N1CCNCC1, amount is: 0.006459999829530716 MOLE;aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], amount is: 0.006459999829530716 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.000775999971665442 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.000775999971665442 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0005169999785721302 MOLE.Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (0.116 g, 0.52 mmol) was added to a stirred mixture of 4-bromo-1-methoxy-2-nitrobenzene (1.5 g, 6.46 mmol), 1-(piperazin-1-yl)ethanone (0.829 g, 6.46 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.449 g, 0.78 mmol) and cesium carbonate (4.21 g, 12.93 mmol) dissolved in dioxane (10 mL) , degased and under argon. The resulting suspension was stirred at 120 °C for 2 hours.At 25°C, the mixture was filtered and evaporated under reduce pressure.The mixture was adsorbed on silica gel.The crude product was purified by flash chromatography on silica gel eluting with 1 to 5% methanol in ethyle acetate. The solvent was evaporated to dryness to afford 1-(4-(4-methoxy-3-nitrophenyl)piperazin-1-yl)ethanone (1.400 g, 78 %) as a orange solid. |
Here is a chemical reaction formula: Reactants are aryl halide:COC1=C(C=C(C=C1)Br)[N+](=O)[O-], amount is: 0.1289999932050705 MOLE;amine:CC(=O)N1CCNCC1, amount is: 0.1289999932050705 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.01549999974668026 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.01549999974668026 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.010300000198185444 MOLE.Products are 0:CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)OC)[N+](=O)[O-], please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: diacetoxypalladium (2.322 g, 10.34 mmol) was added to a stirred suspension of 4-bromo-1-methoxy-2-nitrobenzene (30 g, 129.29 mmol), 1-(piperazin-1-yl)ethanone (16.57 g, 129.29 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (8.98 g, 15.52 mmol) and cesium carbonate (84 g, 258.59 mmol) dissolved in dioxane (300 mL) , degased and under argon. The resulting suspension was stirred at 120 °C for 2 hours.At 25°C, the mixture was filtered and adsorbed on silica gel .The crude product was purified by flash chromatography on silica gel eluting with 1 to 5% methanol in ethyle acetate. The solvent was evaporated to dryness to afford 1-(4-(4-methoxy-3-nitrophenyl)piperazin-1-yl)ethanone (31.0 g, 86 %) as a orange solid. |
Here is a chemical reaction formula: Reactants are aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.03139999881386757 MOLE;amine:CONC(=O)C1=CC=CC=C1N, amount is: 0.05339999869465828 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0031399999279528856 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0031399999279528856 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0015699999639764428 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.817 g, 3.14 mmol), diacetoxypalladium (0.353 g, 1.57 mmol), 2-amino-N-methoxybenzamide (8.87 g, 53.39 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (12 g, 31.40 mmol) and cesium carbonate (20.46 g, 62.81 mmol) were weighed out in a round bottom flask. dioxane (130 mL) was added and argon was let to bubble in the mixture for 10 minutes. The suspension was stirred at 100 °C overnight. The reaction mixture was allowed to cool to room temperature under stirring, diluted with ethyl acetate and the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. (Insolubles~19g). The crude product (30g) was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness, giving a gummy foam EN02972-52-01 (15 g, 35.7 mmol, 114 %): not pure. It was repurified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness to give to batches: one pure EN02972-52-02 (12 g, 28.5 mmol, 91 %), one less pure EN02972-52-03 (0.8 g, 1.903 mmol, 6.06 %). The foam EN02972-52-02 (12 g, 28.5 mmol, 91 %) was dissolved in hot EtOH (12mL). Crystallisation occurred. The resulting crystalline solid was collected by filtration and dried to a constant weight to afford EN02972-52-04 (8.7 g, 19.04 mmol, 60.6 %) as a white crystalline solid. Its filtrate was combined with EN02972-52-03 (0.8 g, 1.903 mmol, 6.06 %) and vacced down. The solid was taken up into EtOH, collected by filtration to give a second crop as a white solid EN02972-52-05 (1.88 g, 4.47 mmol, 14.24 %). |
Here is a chemical reaction formula: Reactants are amine:CONC(=O)C1=CC=CC=C1N, amount is: 0.008899999782443047 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.005229999776929617 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0005230000242590904 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.0005230000242590904 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.00026199998683296144 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.303 g, 0.52 mmol), diacetoxypalladium (0.059 g, 0.26 mmol), 2-amino-N-methoxybenzamide (1.479 g, 8.90 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (2 g, 5.23 mmol) and cesium carbonate (3.41 g, 10.47 mmol) were weighed out in a round bottom flask. dioxane (60 mL) was added and argon was let to bubble in the mixture for 10 minutes. The suspension was stirred at 100 °C overnight. The reaction mixture was allowed to cool to room temperature under stirring, diluted with dichloromethane and methanol, silicagel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (150g) eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness, giving a gummy foam. 35 mL of tBuOMe was added and the resulting solution was stirred at rt for 3 hours. The resulting precipitate was collected by filtration, washed with tBuOMe and dried to a constant weight to afford EN02430-89-01 (1.53 g, 3.64 mmol, 69.5 %) as a white solid, which was contained DCM and EtOAc. It was taken up into a minimum of MeCN, heated to 100°C and MeCN was added until complete solubilisation. The solution was filtered and left to cool to rt overnight. The crystallized product was collected by filtration and dried to constant weight under high vacuum (7.10-2mbar) at 50°C for 1h, to give EN02430-89-02 (1.2 g, 2.63 mmol, 50.2 %) as a crystalline white solid. The filtrate was concentrated, triturated in MeCN and the resulting solid was collected by filtration to give EN02430-89-03 (0.2 g, 0.476 mmol, 9.09 %) - a second crop - as a white solid. 1g of EN02430-89-02 (1.2 g, 2.63 mmol, 50.2 %), EN02430-89-03 (0.2 g, 0.476 mmol, 9.09 %) & EN02430-89-04 (48 mg, 0.114 mmol, 2.182 %) were combined, stirred in boiling water (100 mL) for 10 minutes, cooled down, collected by filtration and dried under vacuum (7.10-2mbar) at 50°C in presence of P2O5, to give EN02430-89-05 (1.1 g, 2.56 mmol, 49.0 %) |
Here is a chemical reaction formula: Reactants are amine:COC1=CC=CC(=C1C(=O)NOC)N, amount is: 0.0006670000148005784 MOLE;aryl halide:CC1=NN(C=C1NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.0003929999948013574 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 5.8900001022266224e-05 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 5.8900001022266224e-05 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 3.529999958118424e-05 MOLE.Products are 0:CC1=NN(C=C1NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NOC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (34.1 mg, 0.06 mmol), diacetoxypalladium (7.93 mg, 0.04 mmol), 2-amino-N,6-dimethoxybenzamide (131 mg, 0.67 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) and cesium carbonate (256 mg, 0.79 mmol) were weighed out in a µwave vial, sealed and dioxane (5 mL) was added. Argon was let to bubble in the mixture for 5 minutes. The reaction was stirred at 90 °C overnight. The reaction mixture was allowed to cool to room temperature, diluted with dichloromethane and MeOH, silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (25g) eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness. The residue was triturated in diethyl ether (gummy in tBuOMe) and the resulting precipitate was collected by filtration, washed with diethyl ether and dried to a constant weight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (131 mg, 74.1 %) as a off-white solid. |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.04910000041127205 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.03269999846816063 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.003269999986514449 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.003269999986514449 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.0016400000313296914 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A suspension of 2-amino-6-methoxy-N-methylbenzamide (8.84 g, 49.07 mmol), N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (12.5 g, 32.71 mmol), diacetoxypalladium (0.367 g, 1.64 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.893 g, 3.27 mmol) and cesium carbonate (19.18 g, 58.88 mmol) in dioxane (130 mL) was degassed with argon, which was also let to bubble for 10 minutes then stirred at reflux for 6h. The reaction mixture was allowed to cool to rt, the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. (Insolubles~23g). The crude product (20g) was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness to afford a foam (7.9g) which was taken up into dichloromethane (40ml) (no time to get dissolved, it crashed out very quickly) and sonicated for 5 minutes. The resulting precipitate was collected by filtration, washed with dichloromethane and dried under vacuum at 50°C to a constant weight to afford 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-6-methoxy- N-methylbenzamide (6.53 g, 46.0 %) as a white solid. The filtrate was concentrated to dryness (residue weight: 700mg), taken up into DCM and collected by filtration to give a second sample EN02972-51-02 (0.36 g, 0.829 mmol, 2.53 %). |
Here is a chemical reaction formula: Reactants are amine:CNC(=O)C1=C(C=CC=C1OC)N, amount is: 0.1080000028014183 MOLE;aryl halide:CC1=NN(C(=C1)NC2=NC=C(C(=C2)I)C(F)(F)F)C, amount is: 0.07199999690055847 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.007199999876320362 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 0.007199999876320362 MOLE;metal and ligand:CC(=O)O.CC(=O)O.[Pd], amount is: 0.003599999938160181 MOLE.Products are 0:CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=C(C(=CC=C3)OC)C(=O)NC)C(F)(F)F)C, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 2-amino-6-methoxy-N-methylbenzamide (19.45 g, 107.95 mmol), N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (27.5 g, 71.97 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.16 g, 7.20 mmol) diacetoxypalladium (0.808 g, 3.60 mmol) and cesium carbonate (42.2 g, 129.54 mmol) were suspended in dioxane (300 mL). The reaction was degased, purged with argon sereval times and heated to 95 °C overnight. The reaction mixture was allowed to cool to rt, the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. The resulting residue was triturated with dichloromethane (150 ml), filtered, washed with DCM to give EN03299-47-01 (8.5 g, 19.57 mmol, 27.2 %) The filtrate was purified by flash chromatography on silica gel eluting with AcOEt and 5% methanol in ethyl acetate. Solvent were evaporated. The resulting precipitate was collected by filtration, washed with dichloromethane and dried to afford EN03299-47-02 (4.5 g, 10.36 mmol, 14.39 %). Not enought combined with _EN03299-49_ |
Here is a chemical reaction formula: Reactants are amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, amount is: 0.0004830000107176602 MOLE;aryl halide:CC1C2=C(N=C(C=C2)Cl)OC(CN1C)C3CC3, amount is: 0.0004830000107176602 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.0007239999831654131 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 2.409999979136046e-05 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 1.2100000276404899e-05 MOLE.Products are 0:CC1C2=C(N=C(C=C2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)OC(CN1C)C5CC5, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: 8-chloro-2-cyclopropyl-4,5-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (122 mg, 0.48 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (99 mg, 0.48 mmol), Pd2dba3 (11.05 mg, 0.01 mmol), BINAP (15.03 mg, 0.02 mmol) and SODIUM TERT-BUTOXIDE (69.6 mg, 0.72 mmol) were weighed in to a microwave vial, the vial was capped and flushed with argon. toluene (4 mL) was added and the mixture was heated to 100°C in a microwaver apparatus for 2 h. The cooled reaction mixture was diluted with dichloromethane and filtered. The mixture was concentrated and purified by column chromatography on Silica, using gradient elution with increasing concentration of methanol, from 0 to 8 %, in dichloromethane to give a mixture of the two diastereomers. This was then subjected to diastereo and enantio separation to give 31 mg of isomer 1, 32.6 mg of isomer 2, 29 mg of isomer 3 and 29.7 mg of isomer 4 of 2-cyclopropyl-N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4,5-dimethyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (Total Yield 122.3 mg, 60 %). |
Here is a chemical reaction formula: Reactants are aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F, amount is: 0.04780000075697899 MOLE;amine:C1CNCCN1, amount is: 0.28700000047683716 MOLE,Reagents are Base:CC(C)(C)[O-].[Na+], amount is: 0.06689999997615814 MOLE,Solvents are Solvent:CC1=CC=CC=C1, amount is: 0.0 ,Catalysts are metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8, amount is: 0.004780000075697899 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 0.0011899999808520079 MOLE.Products are 0:C1CN(CCN1)C2=CC(=C(C=C2)OCC3=CC=CC=C3)F, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: sodium 2-methylpropan-2-olate (6.43 g, 66.88 mmol) was added to 1-(benzyloxy)-4-bromo-2-fluorobenzene (13.43 g, 47.77 mmol) and piperazine (24.69 g, 286.64 mmol) in toluene (140 mL). The resulting mixture was bubbled with nitrogen for 10 minutes then 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (2.97 g, 4.78 mmol) and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (1.094 g, 1.19 mmol) were added and the mixture was stirred at 110 °C for 20 hours. The reaction mixture was cooled to room temperature then fitered through celite and the filter cake washed with ethyl acetate (500 mL). The filtrate was evaporated to give crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% MeOH in DCM. Pure fractions were evaporated to dryness to afford 1-(4-(benzyloxy)-3-fluorophenyl)piperazine (9.80 g, 71.6 %) as a solid. |
Here is a chemical reaction formula: Reactants are aryl halide:C1COCCN1C2=CC(=O)N3C=CC=C(C3=N2)C4=CC=CC5=C4SC6=C5C=C(C=C6)OS(=O)(=O)C(F)(F)F, amount is: 0.00017800000205170363 MOLE;amine:CNC(=O)CN1CCOCC1, amount is: 0.00021399999968707561 MOLE,Reagents are Base:C(=O)([O-])[O-].[Cs+].[Cs+], amount is: 0.0007120000082068145 MOLE,Solvents are Solvent:C1COCCO1, amount is: 0.0 ,Catalysts are metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C, amount is: 8.89999955688836e-06 MOLE;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], amount is: 4.44999977844418e-06 MOLE.Products are 0:CN(C1=CC2=C(C=C1)SC3=C2C=CC=C3C4=CC=CN5C4=NC(=CC5=O)N6CCOCC6)C(=O)CN7CCOCC7, please give me the reaction condition of this chemical formula. | The condition of this chemical reaction is: A solution of 6-(2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)dibenzo[b,d]thiophen-2-yl trifluoromethanesulfonate (100mg, 0.18 mmol) in dry dioxane (1 ml) was added to a stirred mixture of N-methyl-2-morpholinoacetamide (33.8 mg, 0.21 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (4.08 mg, 4.45 µmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.15 mg, 8.90 µmol) and cesium carbonate (232 mg, 0.71 mmol) in dry dioxane (1 ml) . The resulting mixture was stirred under nitrogen at 110 °C for 3 hours. UPLC analysis showed no appreciable product only hydrolysis of the triflate - not isolated , reaction abandonned |