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Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:COC1=CC(=CC=C1)Br, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC=C4)OC)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.93 mg, 0.02 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (130 mg, 0.35 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.25 mg, 0.03 mmol), 1-bromo-3-methoxybenzene (0.055 ml, 0.44 mmol) and cesium carbonate (171 mg, 0.52 mmol) dissolved in 1,4-dioxane (4 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in V-10 Evaporator (Biotage) The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(3-methoxyphenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (46.0 mg, 27.5 %) as a solid. |
Here is a chemical reaction formula: Reactants are:amine:C1=CC=C(C=C1)N;aryl halide:C1=CC=C(C(=C1)[N+](=O)[O-])Br, Reagents 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;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];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1=CC=C(C=C1)NC2=CC=CC=C2[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 200 mL roundbottom flask was charged with 1-bromo-2-nitrobenzene (Alfa Aesar; 2.10 g, 10.40 mmol), Pd2(dba)3 (Aldrich; 119.6 mg, 2.5 mol%), racemic BINAP (Strem; 197.8 mg, 3.1 mol%), and cesium carbonate (Aldrich; 4.87 g, 14.95 mmol). The flask was evacuated and backfilled with N2 (3x), and then anhydrous toluene (20 mL) was added. Aniline (Acros; 1.20 mL, 13.2 mmol) was added followed by additional toluene (30 mL), and the mixture was allowed to stir at room temperature for 5 minutes before being placed in a 100 °C oil bath. After heating overnight, the reaction was allowed to cool and was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2x), and the combined organics were concentrated under reduced pressure. The crude material was purified by silica gel chromatography (gradient elution; Rf in 90:10 hexanes:EtOAc = 0.54) to give a red-orange solid. 1.89 g of solid was collected. |
Here is a chemical reaction formula: Reactants are:amine:CC1=CN(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CC1=CSC(=N1)C2CN(CC3=C(O2)N=C(C=C3)Cl)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC1=CN(C=N1)C2=C(N=C(C=C2)NC3=NC4=C(CN(CC(O4)C5=NC(=CS5)C)C)C=C3)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 8-chloro-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (120 mg, 0.41 mmol) in DME (3 mL) were 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (83 mg, 0.41 mmol), cesium carbonate (198 mg, 0.61 mmol), 2-(Dicyclohexylphosphino)biphenyl (14.22 mg, 0.04 mmol) and Palladium acetate (9.11 mg, 0.04 mmol) added. The reaction was heated to 110°C for 180 min under N2 atmosphere. The solids were filtered off and washed with DCM, the solvents were evaporated and the crude product was purified by silica flash chromatography, MeOH, 0-10%, in DCM yielding N-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (20.00 mg, 10.63 %) |
Here is a chemical reaction formula: Reactants are:aryl halide:CC1=CSC(=N1)C2CN(CC3=C(O2)N=C(C=C3)Cl)C;amine:CC1=CN(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CC1=CN(C=N1)C2=C(N=C(C=C2)NC3=NC4=C(CN(CC(O4)C5=NC(=CS5)C)C)C=C3)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 8-chloro-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (50 mg, 0.17 mmol) in DME (3 mL) were 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (34.5 mg, 0.17 mmol), cesium carbonate (83 mg, 0.25 mmol), 2-(Dicyclohexylphosphino)biphenyl (5.92 mg, 0.02 mmol) and Palladium acetate (3.80 mg, 0.02 mmol) added. The reaction was heated to 110°C for 90 min under N2 atmosphere. The solids were filtered off and washed with DCM, the solvents were evaporated and the crude product was purified by silica flash chromatography, MeOH, 0-10%, in DCM yielding N-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (16.00 mg, 20.42 %) |
Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=C(C=CC(=C1)Br)I;amine:C1COCCN1, Reagents are:Solvent:COCCOC;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=C(C=CC(=C1)Br)N2CCOCC2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of methyl 5-bromo-2-iodobenzoate (2.1 g, 6.16 mmol) in DME (15 mL) were morpholine (0.593 mL, 6.78 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.384 g, 0.62 mmol), Palladium acetate (0.138 g, 0.62 mmol) and CESIUM CARBONATE (2.81 g, 8.62 mmol) added. The mixture was heated in the microwave oven for 1h. The solvent was evaporated and the crude product was added to a silica gel column, 0-25% EtOAc in heptane yielding [Products] |
Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:COC(=O)C1=CC(=C(C=C1)I)Br, Reagents are:Solvent:COCCOC;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC(=C(C=C1)N2CCOCC2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of methyl 3-bromo-4-iodobenzoate (1.981 g, 5.81 mmol) in DME (10 mL) were morpholine (0.559 mL, 6.39 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.362 g, 0.58 mmol), Palladium acetate (0.130 g, 0.58 mmol) and CESIUM CARBONATE (3.79 g, 11.62 mmol) added. The mixture was heated in the microwave oven for 12h at 110°C. The solids were filtered off through celite, the solvent was evaporated and the crude product was added to a silica gel column, 0-30% EtOAc in heptane yielding methyl 3-bromo-4-morpholinobenzoate (0.566 g, 32.5 %) |
Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC(=C1)Br)F, Reagents are:Solvent:C1COCCO1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.93 mg, 0.02 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (130 mg, 0.35 mmol), 1-bromo-3-fluorobenzene (0.049 ml, 0.44 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.25 mg, 0.03 mmol) and cesium carbonate (171 mg, 0.52 mmol) dissolved in 1,4-dioxane (4 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 16 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in V-10 Evaporator (Biotage) The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (67.0 mg, 41.1 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=CC1=O)C2=C(N=C(C=C2)N)OC, Reagents are:Base:CCC(C)(C)[O-].[Na+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(C(=O)C=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (300 mg, 1.09 mmol), 5-(6-amino-2-methoxypyridin-3-yl)-1-methylpyridin-2(1H)-one (253 mg, 1.09 mmol), Palladium(II) acetate (24.51 mg, 0.11 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (63.2 mg, 0.11 mmol) and Sodium tert-pentoxide (144 mg, 1.31 mmol) were mixed in dioxane (3 mL) and run in a microwave reactor for 40 min at 120°C. the mixture was filtered thru celite and concetrated. purified using flash column chromatography using 0-6 % MeOH (1% NH3) in DCM. |
Here is a chemical reaction formula: Reactants are:amine:CN(C)CCOC1=CN=C(C=C1)N;aryl halide:CC1=C(N=CN=C1Cl)N2C=NC3=CC=CC=C32, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;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;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], and Products are 0:CC1=C(N=CN=C1N2C=NC3=CC=CC=C32)NC4=NC=C(C=C4)OCCN(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (44.2 mg, 0.05 mmol) was added to 5-(2-(dimethylamino)ethoxy)pyridin-2-amine (175 mg, 0.97 mmol), 1-(6-chloro-5-methylpyrimidin-4-yl)-1H-benzo[d]imidazole (236 mg, 0.97 mmol), sodium t-butoxide (139 mg, 1.45 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (84 mg, 0.14 mmol) in toluene (10 mL) at 20°C under nitrogen. The resulting suspension was stirred at 100 °C for 16 hours then cooled to room temperature. LCMS analysis indicates no SM, product peak present. The reaction mixture was diluted with DCM/MeOH, filtered and filtrate concentrated _in vacuo_. The residue was dissolved in DCM (100 mL) and washed with water (100 mL). The organic layer was passed through phase separating cartridge and concentrated under reduced pressure. 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-(1H-benzo[d]imidazol-1-yl)-N-(5-(2-(dimethylamino)ethoxy)pyridin-2-yl)-5-methylpyrimidin-4-amine (67.0 mg, 17.82 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)CC(F)(F)F;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:Solvent:COCCOC;metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C;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];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)CC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A reaction mixture of 8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.605 g, 2.16 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.440 g, 2.16 mmol), Cs2CO3 (1.053 g, 3.23 mmol), Tri-t-butylphosphonium tetrafluoroborate (0.063 g, 0.22 mmol) and Bis(dibenzylideneacetone)palladium (0.062 g, 0.11 mmol) in DME (20 mL) was flushed with argon and run in the microwave at 120°C for 60 minutes. Have unreacted startingmaterial left. Added Tri-t-butylphosphonium tetrafluoroborate (0.063 g, 0.22 mmol) and Bis(dibenzylideneacetone)palladium (0.062 g, 0.11 mmol) and ran the vial at 120°C for another hour. The mixture was filtered through celite and washed with DCM. The solvent was evaporated and the crude prouduct was purified by silica flash chromatography using a gradient of metanol (0 to 5%) in dichloromethane giving N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (0.483 g, 50.0 %). |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)CC(F)(F)F;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C;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];Solvent:COCCOC, and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)CC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A reaction mixture of 8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.044 g, 0.09 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.019 g, 0.09 mmol), Cs2CO3 (0.046 g, 0.14 mmol), Tri-t-butylphosphonium tetrafluoroborate (2.73 mg, 9.41 µmol) and Bis(dibenzylideneacetone)palladium (2.70 mg, 4.70 µmol) in DME (2 mL) was flushed with argon and stirred at rt overnight. No product according to LCMS. The reaction mixture was then run in the microwave at 120°C for 30 minutes. Have unreacted startingmaterial left. Ran the sample again at 120°C for 30 minutes. Doesn´t seem as if the microwave warmed the vial. Added Tri-t-butylphosphonium tetrafluoroborate (2.73 mg, 9.41 µmol) and Bis(dibenzylideneacetone)palladium (2.70 mg, 4.70 µmol) and ran the vial at 120°C for 1 hr. Reaction complete. The mixture was filtered through celite and washed with DCM. The solvent was evaporated and the crude prouduct was purified by silica flash chromatography using a gradient of metanol (0 to 5%) in dichloromethane giving N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (0.036 g, 85 %). |
Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)CC(F)(F)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)CC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (60 % purity, 314 mg, 0.67 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (137 mg, 0.67 mmol), PALLADIUM(II) ACETATE (15.07 mg, 0.07 mmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (23.53 mg, 0.07 mmol) and Cs2CO3 (328 mg, 1.01 mmol) were placed in a microwave vial. The vial was capped and flushed with argon. DME (3 mL) was added via a syringe and the resulting mixture was heated to 100°C in a microwave apparatus for 2 h. The reaction mixture was diluted with dichloromethane, filtered and concentrated. The residue was purified first by column chromatography using Silica stationary phase and gradient elution with increasing concentration of methanol, from 0 to 8 %, in dichloromethane, and then by reversed phase HPLC to give N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (102 mg, 33.9 %). |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)CC(F)(F)F;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)CC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A reaction mixture of 8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.341 g, 1.21 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.248 g, 1.21 mmol), PALLADIUM(II) ACETATE (0.027 g, 0.12 mmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.043 g, 0.12 mmol) and Cs2CO3 (0.594 g, 1.82 mmol) in DME (2 mL) was degassed and flushed with argon in a microwave vial. The reaction mixture was stirred at 110°C for 1 hr. The reaction mixture was filtrated through celite, washed with DCM and concentrated. The crude product was purified by silica flash chromatography using a gradient of methanol (0 to 5%) in DCM giving N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (0.200 g, 36.7 %). |
Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CC1C(OC2=C(CN1C)C=CC(=N2)Cl)C3=NC(=CS3)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC1C(OC2=C(CN1C)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=NC(=CS5)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.086 g, 0.42 mmol) in DME (3 mL) were 8-chloro-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.130 g, 0.42 mmol), cesium carbonate (0.205 g, 0.63 mmol), 2-(Dicyclohexylphosphino)biphenyl (0.015 g, 0.04 mmol) and Palladium acetate (9.42 mg, 0.04 mmol) added. The reaction was heated to 110°C for 60 min under argon atmosphere. The reaction mixture was filtered through celite, washed with DCM and the solvents were evaporated. The crude product was purified by silica flash chromatography, MeOH, 0-5%, in DCM yielding N-(6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-3,4-dimethyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (0.147 g, 73.4 %). The product was submitted to the prepgroup for chiral separation. |
Here is a chemical reaction formula: Reactants are:amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC(=C1)Br)F, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.33 mg, 0.01 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (121 mg, 0.34 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (16.61 mg, 0.03 mmol), 1-bromo-3-fluorobenzene (0.047 ml, 0.42 mmol) and cesium carbonate (165 mg, 0.51 mmol) suspended in 1,4-dioxane (3.329 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 20 hours _(_ _UPLC/MS O/N showed that the SM was almost consumed)._ The reaction mixture was allowed to cool to room temperature, the crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 7% Propanol-CH2Cl2. The solvent was evaporated to dryness to afford methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (120 mg, 79 %) as a yellow oil which solidified on standing. |
Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:COC1=C(C=C(C(=C1)Cl)C(=O)OC)Br, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC1=C(C=C(C(=C1)Cl)C(=O)OC)N2CCOCC2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium(II) acetate (0.040 g, 0.18 mmol), methyl 2-chloro-4-methoxy-5-morpholinobenzoate (2.042 g, 80 %), cesium carbonate (4.08 g, 12.52 mmol) and racemic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.223 g, 0.36 mmol) were mixed together in a round bottom flask and evacuated then purged with nitrogen. Morpholine (0.780 mL, 8.94 mmol) and degassed toluene (15 mL) were added and the resulting suspension (orange/red) was degassed and purged with nitrogen 3 times. The mixture was heated to 100 °C under nitrogen overnight. The mixture was allowed to cool to ambient temperature and filtered, washing with EtOAc. The filtrate was concentrated and the crude residue (a dark orange gum) was purified by flash silica chromatography, elution gradient 0 to 40% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-chloro-4-methoxy-5-morpholinobenzoate (2.042 g, 80 %) as a pale yellow/cream crystalline solid. |
Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:COC1=C(C=C(C(=C1)Cl)C(=O)OC)Br, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:COC1=C(C=C(C(=C1)Cl)C(=O)OC)N2CCOCC2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Methyl 5-bromo-2-chloro-4-methoxybenzoate (1.486 g, 5.32 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.132 g, 0.21 mmol), palladium(II) acetate (0.024 g, 0.11 mmol) and cesium carbonate (2.425 g, 7.44 mmol) were mixed together and evacuated then purged with nitrogen. Toluene (10 mL) and morpholine (0.464 mL, 5.32 mmol) were added and the mixture evacuated and purged with nitrogen several times. The suspension (red) was heated to 100 °C for 18 hours under nitrogen. The mixture was allowed to cool to ambient temperature and filtered, washing with EtOAc. The filtrate was concentrated to provide an orange residue. The crude product was purified by flash silica chromatography, elution gradient 0 to 35% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-chloro-4-methoxy-5-morpholinobenzoate (0.826 g, 54.4 %) as a cream crystalline solid. Lower than expected yield (previously recorded 80% EN04398-06).....not sure what has happened. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=C(C(=C1)Cl)C(=O)OC)Br;amine:C1COCCN1, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC1=C(C=C(C(=C1)Cl)C(=O)OC)N2CCOCC2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Cesium carbonate (3.78 g, 11.61 mmol), methyl 5-bromo-2-chloro-4-methoxybenzoate (2.317 g, 8.29 mmol), palladium(II) acetate (0.037 g, 0.17 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.206 g, 0.33 mmol) were combined and evacuated and purged with nitrogen (3 times). Degassed toluene (30 mL) and morpholine (0.723 mL, 8.29 mmol) was added and the resulting suspension was evacuated and purged with nitrogen several times. The reaction mixture was heated to 100 °C under nitrogen for 22 hours. The reaction was allowed to cool to ambient temperature and filtered through a celite pad, washing with EtOAc. The filtrate was concentrated and the crude product purified by flash silica chromatography, elution gradient 10 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-chloro-4-methoxy-5-morpholinobenzoate (1.865 g, 79 %) as a cream crystalline solid. |
Here is a chemical reaction formula: Reactants are:amine:C1=CC2=C(C=NN2C=C1)C3=NC(=NC=C3Cl)N;aryl halide:COC1=C(C=C(C=C1)[N+](=O)[O-])Br, Reagents 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;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];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:COC1=C(C=C(C=C1)[N+](=O)[O-])NC2=NC=C(C(=N2)C3=C4C=CC=CN4N=C3)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: _Crude SM used_ 2-bromo-1-methoxy-4-nitrobenzene (0.029 g, 0.13 mmol), 5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (0.031 g, 0.125 mmol) and cesium carbonate (0.057 g, 0.18 mmol) were suspended in dry dioxane (2 mL) the mixture degassed with nitrogen for 10 minutes. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (6.87 mg, 7.50 µmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.79 mg, 10.00 µmol) were added and the mixture was sealed into a microwave tube. The reaction was heated to 150 °C for 2 hours in the microwave reactor and cooled to RT. Possibly product - not very much. The reaction was heated to 150 °C for 10 hours in the microwave reactor and cooled to RT. Product now c4%, both starting materials still present. Not continued. |
Here is a chemical reaction formula: Reactants are:amine:C1=CC2=C(C=NN2C=C1)C3=NC(=NC=C3Cl)N;aryl halide:COC1=C(C=C(C=C1)[N+](=O)[O-])Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;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];Solvent:C1COCCO1, and Products are 0:COC1=C(C=C(C=C1)[N+](=O)[O-])NC2=NC=C(C(=N2)C3=C4C=CC=CN4N=C3)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: _Crude SM used_ 2-bromo-1-methoxy-4-nitrobenzene (0.029 g, 0.13 mmol), 5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (0.031 g, 0.125 mmol) and cesium carbonate (0.057 g, 0.18 mmol) were suspended in dry dioxane (2 mL) the mixture degassed with nitrogen for 10 minutes. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.034 g, 0.04 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.029 g, 0.05 mmol) were added and the mixture was sealed into a microwave tube. The reaction was heated to 150 °C for 2 hours in the microwave reactor and cooled to RT. Possibly product - not very much. The reaction was heated to 150 °C for 10 hours in the microwave reactor and cooled to RT. Product now c4%, both starting materials still present. Not continued. |
Here is a chemical reaction formula: Reactants are:amine:C1C[C@@H](C2=NC(=NN2C1)N)C3=CC=C(C=C3)F;aryl halide:CN(C)C(=O)CC1=CC=C(C=C1)Br, Reagents are:metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)C(=O)CC1=CC=C(C=C1)NC2=NN3CCCC(C3=N2)C4=CC=C(C=C4)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (94 mg, 0.40 mmol), 2-(4-bromophenyl)-N,N-dimethylacetamide (103 mg, 0.40 mmol), Cesium carbonate (198 mg, 0.61 mmol), Palladium(II) acetate (9.09 mg, 0.04 mmol) and 2-(Dicyclohexylphosphino)biphenyl (14.18 mg, 0.04 mmol) were added to a 0.5-2 mL microwave vial. The vial was capped and flushed with nitrogen. dioxane (3 mL) was added and the vial was flushed with additional nitrogen before it was heated by microwave irradiation at 120°C for 1.5h. The reaction mixture was cooled to r.t. and water and EtOAc were added and the layers were separated. The aqueous phase was extracted with EtOAc (3x). The combined organic phases were washed with brine, dried (phase separator) and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using a gradient of 0-3% MeOH in EtOAc over 12 min. The desired fractions were combined to result in 2-(4-(8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)phenyl)-N,N-dimethylacetamide (51.0 mg, 32.0 %) |
Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)C3CC(C3)(F)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5CC(C5)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium(II) acetate (0.019 g, 0.08 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (0.096 g, 0.17 mmol) were added to a degassed solution of 8-chloro-2-(3,3-difluorocyclobutyl)-4-methyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.160 g, 0.55 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.113 g, 0.55 mmol) and Cesium carbonate (0.058 mL, 0.72 mmol) in dry dioxane (15 mL). The reaction was heated in a microwave oven at 145°C for 1h. About 50% of product. The reaction was heated at 145°C for another 30 min. About 45% of product. The reaction was interrupted and the reaction mixture was pooled with the corresponding mixture in EN04426-52. The reaction mixture was filtered through a plug of celite. The celite was washed with DCM. The solvents were evaporated and the crude was purified by ISCO on a 25 g column with an increased gradient of DCM/MeOH (90/10) 0-50% in DCM) to give 0.176 g (35%) of the product. The enatiomers were also separated (see EN04426-56). |
Here is a chemical reaction formula: Reactants are:amine:C1=CC(=C(C=C1Cl)N)C#N;aryl halide:C1=CC(=NC(=C1)Cl)Cl, Reagents are:Solvent:CC1=CC=CC=C1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[K+].[K+], and Products are 0:C1=CC(=NC(=C1)Cl)NC2=C(C=CC(=C2)Cl)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 2,6-dichloropyridine (2 g, 13.51 mmol), 2-amino-4-chlorobenzonitrile (2.062 g, 13.51 mmol), PALLADIUM(II) ACETATE (0.303 g, 1.35 mmol), BINAP (1.683 g, 2.70 mmol) and potassium carbonate (5.60 g, 40.54 mmol) in toluene (100 mL) was stirred at reflux under N2 for 5hrs. LCMS detected major peak as desire product. The resulting suspension was cooled, filtered, and the filtrate was concentrated under reduced pressure. Column chromatography of the residue on silica gel using 15% to 20% ethyl acetate in hexane, then 100% ethyl acetate as eluent gave the crude product which was recrystallized from methanol/DCM to yield a light yellow solid as desired product 4-chloro-2-(6-chloropyridin-2-ylamino)benzonitrile (3.34 g, 93 %) |
Here is a chemical reaction formula: Reactants are:amine:CC1=C(C=CC(=N1)S(=O)(=O)C)N;aryl halide:CC(C)OC(=O)N1CCC(CC1)OC2=C(C(=NC=N2)Cl)OC, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3OC4=CC=CC=C4P(C5=CC=CC=C5)C6=CC=CC=C6;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=C(C=CC(=N1)S(=O)(=O)C)NC2=C(C(=NC=N2)OC3CCN(CC3)C(=O)OC(C)C)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Bis[(2-diphenylphosphino)phenyl] ether (0.274 g, 0.51 mmol) was added in one portion to Palladium(II) acetate (0.057 g, 0.25 mmol) in toluene (5 mL) (degassed by bubbling N2 through it for 30 minutes) at 20°C under nitrogen (this mixture was also degassed by vacuum / N2 six times). After a few minutes a yellow suspension had formed. This was added by pipette to a mixture of isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (4.19 g, 12.71 mmol), 2-methyl-6-(methylsulfonyl)pyridin-3-amine (2.366 g, 12.71 mmol) and Sodium tert-butoxide (2.333 mL, 19.06 mmol) in toluene (40 mL) at 60°C under nitrogen. The resulting mixture was degassed using N2 / vacuum six times. The resulting suspension was stirred at 60 °C for 18 hours. Sodium tert-butoxide (2.333 mL, 19.06 mmol) was added to the reaction mixture followed by another amount of pre-formed catalyst using Bis[(2-diphenylphosphino)phenyl] ether (0.274 g, 0.51 mmol) was added in one portion to Palladium(II) acetate (0.057 g, 0.25 mmol) in toluene (5 mL) as above. The mixture was heated at 60°C for 7 hours then further catalyst added using Bis[(2-diphenylphosphino)phenyl] ether (0.274 g, 0.51 mmol) was added in one portion to Palladium(II) acetate (0.057 g, 0.25 mmol) in toluene (5 mL) as above. The mixture was stirred at 60°C for 18 hours. Work up was by diluting with water (30 ml) and DCM (100 ml) then filtering through a pad of celite and washing through well with DCM (6 x 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 100% EtOAc in heptane (material applied in DCM). Pure fractions were evaporated to dryness to leave a yellow solid, EN05005-04-01. The solid was triturated with Et2O (20 ml) and the solid filtered off and washed with Et2O (2 x 10ml) then heptane ( 2 x 10ml) to afford isopropyl 4-(5-methoxy-6-(2-methyl-6-(methylsulfonyl)pyridin-3-ylamino)pyrimidin-4-yloxy)piperidine-1-carboxylate (4.78 g, 78 %), EN05005-04-02, as a white solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:CC(C)OC(=O)N1CCC(CC1)OC2=C(C(=NC=N2)Cl)OC;amine:CC1=C(C=CC(=N1)S(=O)(=O)C)N, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3OC4=CC=CC=C4P(C5=CC=CC=C5)C6=CC=CC=C6;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=C(C=CC(=N1)S(=O)(=O)C)NC2=C(C(=NC=N2)OC3CCN(CC3)C(=O)OC(C)C)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Bis[(2-diphenylphosphino)phenyl] ether (0.021 g, 0.04 mmol) was added in one portion to Palladium(II) acetate (4.33 mg, 0.02 mmol) in toluene (1 mL) (degassed by bubbling N2 through it for 30 minutes) at 20°C under nitrogen. After a few minutes a yellow suspension had formed. This added in one portion by pipette to a mixture of isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (0.318 g, 0.96 mmol), 2-methyl-6-(methylsulfonyl)pyridin-3-amine (0.180 g, 0.96 mmol) and Sodium tert-butoxide (0.177 mL, 1.45 mmol) in toluene (3 mL) at 60°C under nitrogen. The resulting mixture was degassed using N2 / vacuum six times. The resulting suspension was stirred at 60 °C for 18 hours. Work up was by diluting with water (10 ml) and DCM (10 ml) then filtering through a pad of celite and washing through well with DCM (6 x 10 ml). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography (40g column), elution gradient 0 to 100% EtOAc in heptane (material applied in DCM). Pure fractions were evaporated to dryness to afford isopropyl 4-(5-methoxy-6-(2-methyl-6-(methylsulfonyl)pyridin-3-ylamino)pyrimidin-4-yloxy)piperidine-1-carboxylate (0.231 g, 50.0 %) as a slightly off white foam. Trituration with Et2O (10 ml) and sctratching gave a free flowing white suspension. The solvent was removed under reduced pressure to give a white powder. |
Here is a chemical reaction formula: Reactants are:amine:C1=CC=C(C=C1)CN;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:CC(C)(C)[O-].[Na+];metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:C1=CC=C(C=C1)CNC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: palladium(II) acetate (0.018 g, 0.08 mmol), (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (0.066 g, 0.12 mmol), sodium tert-butoxide (0.194 g, 2.02 mmol), phenylmethanamine (0.110 mL, 1.01 mmol) and 2,4-dichloropyridine (0.151 mL, 1.01 mmol) were suspended in DME (4 mL) and sealed into a microwave tube. The reaction was heated to 80 °C for 30 minutes in the microwave reactor and cooled to RT. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=CC=C(C=C1)CN, Reagents are:Solvent:C1COCCO1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1=CC=C(C=C1)CNC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: phenylmethanamine (0.111 mL, 1.01 mmol), 2,4-dichloropyridine (0.151 mL, 1.01 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (70.4 mg, 0.12 mmol) and cesium carbonate (660 mg, 2.03 mmol) were stirred in 1,4-dioxane (5 mL). The mixture was purged with nitrogen for 10 minutes. Palladium(II) acetate (22.76 mg, 0.10 mmol) was added and sealed into a microwave tube. The reaction was heated to 100 °C for 1 hour in the microwave reactor and cooled to RT. The reaction was heated to 100 °C for 1 hour in the microwave reactor and cooled to RT. |
Here is a chemical reaction formula: Reactants are:amine:CC(C)CN;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:CC(C)(C)[O-].[Na+];metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC(C)CNC1=NC=CC(=C1)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: palladium(II) acetate (0.018 g, 0.08 mmol), (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T-BUTYLPHOSPHINE (0.066 g, 0.12 mmol), sodium tert-butoxide (0.194 g, 2.02 mmol), 2-methylpropan-1-amine (0.100 mL, 1.01 mmol) and 2,4-dichloropyridine (0.151 mL, 1.01 mmol) were suspended in DME (4 mL) and sealed into a microwave tube. The reaction was heated to 80 °C for 30 minutes in the microwave reactor and cooled to RT. |
Here is a chemical reaction formula: Reactants are:amine:CC1=CC2=C(N1)C=C(C=C2)OC(F)(F)F;aryl halide:C1=CC=C(C=C1)COC2=CC(=CC=C2)Br, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)(C)P(C1=CC=CC=C1C2=CC=CC=C2)C(C)(C)C;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];Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=CC2=C(N1C3=CC(=CC=C3)OCC4=CC=CC=C4)C=C(C=C2)OC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: EN04773-53, _Buchwald coupling, toluene and bromide_ The indole from 4773-25, 1-(benzyloxy)-3-bromobenzene,Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 100 °C for 2h. Ca 60% conversion according to LCMS (product at 2.31 min). This conversion rate seemed faster than for the corresponding aryliodide. Big bacth was performed in 4773-54. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=CC(=CC=C2)Br;amine:CC1=CC2=C(N1)C=C(C=C2)OC(F)(F)F, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)(C)P(C1=CC=CC=C1C2=CC=CC=C2)C(C)(C)C;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], and Products are 0:CC1=CC2=C(N1C3=CC(=CC=C3)OCC4=CC=CC=C4)C=C(C=C2)OC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: EN04773-54, _Buchwald coupling, toluene and bromide_ The indole from 4773-41, 1-(benzyloxy)-3-bromobenzene,Pd2(dba)3 (5mol%), JohnPhos (10mol%) and KOtBu (1.4eq) were dissolved in toluene. The mixture was warmed at 80 °C for 40 hours.* The reaction was carefully monitored and analysis data from 2h, 4, 16 and 40 h are attached. According to LCMS there were ca 75% conversion to the product. The mixture was washed with water, concentrtaed and purified by silica column (Hep/EtOAc 6:1). The collected fractions contained product (6 g, 62.5% yield) but had some impurity (see TLC and NMR). Nevertheless Friedel crafts acylation was performed without further purifications. See e.g. 4773-56. ### *JohnPhos, pd2(dba)3 and sodium tertbutoxide had been dissolved in toluene and was portionwise added to the reaction mixture during the first 16h. |
Here is a chemical reaction formula: Reactants are:amine:C1CNC1;aryl halide:C1=CC(=CC=C1C#N)Br, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1CN(C1)C2=CC=C(C=C2)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-bromobenzonitrile (1.355 g, 7.44 mmol) and Sodium tert-butoxide (1.073 g, 11.17 mmol) were mixed in toluene (10 mL) and degassed by passing nitrogen for 5 min. Then Azetidine (1 mL, 14.89 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.172 g, 0.30 mmol) and Palladium(II) acetate (0.050 g, 0.22 mmol)were added and the mixture was heated in oilbath at 100°C for 15h. The reaction was complete by GCMS. Filtration through celite washing with CH2Cl2 and evaporation gave a crude product (1g). Purification by chromatography on silica (0-50 % EtOAc in heptane) gave the desired product 4-(azetidin-1-yl)benzonitrile (0.730 g, 62.0 %). |
Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C=CC=N1)Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:metal and ligand:CC(C)OC1=C(C(=CC=C1)OC(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=C(C=CC=N1)N2CCN(CC2)C(=O)OC(C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium acetate (65 mg, 0.29 mmol) and RuPhos (271mg, 0.58mmol) were dissolved in toluene (10 mL), degassed and purged with nitrogen and warmed to 50°C for 15 minutes. In a separate vessel, were mixed 3-bromo-2-methyl pyridine (1.00g, 5.81 mmol), BOC-piperazine (1.08g, 5.81mmol), sodium tertbutoxide and toluene (17 mL). The mixture was degassed, purged with nitrogen and warmed to 50°C. The catalyst was transferred to the reaction vessel and the mixture degassed and purged with nitrogen. The reaction was heated at 100°C overnight under nitrogen. The mixture was filtered through GF/F paper, washing with MeOH. The filtrate was concentrated to provide a dark brown gum. The gum was purified by flash silica chromatography, elution gradient 30 to 80% EtOAc in heptane. Pure fractions were evaporated to provide the desired product as a gum (1.492g, 93%). Rf (1:1 EtOAc/heptane) 0.3 |
Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C=CC=N1)Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:metal and ligand:CC(C)OC1=C(C(=CC=C1)OC(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=C(C=CC=N1)N2CCN(CC2)C(=O)OC(C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: RuPhos (0.543 g, 1.16 mmol) and palladium (II) acetate (0.131 g, 0.58 mmol) were suspended in toluene (15 mL) at ambient temperature. The resulting mixture was degassed and purged several times and warmed to 50°C under nitrogen for 20 mins. In a separate vessel were mixed 3-bromo-2-methylpyridine (2 g, 11.63 mmol), tert-butyl 4-(2-methylpyridin-3-yl)piperazine-1-carboxylate (2.67 g, 83 %), sodium tertbutoxide (1.676 g, 17.44 mmol) and toluene. The mixture was degassed and purged with nitrogen several times and warmed to 50°C. The catalyst solution was added to the reaction vessel and the resulting mixture degassed and purged wtih nitrogen. The reaction was heated at 100°C overnight. The reaction mixture was allowed to cool to ambient temperature and filtered through GF/F paper, washing with MeOH. The filtrate was concentrated to provide the crude material. This was purified by flash silica chromatography, elution gradient 20 to 70% EtOAc in heptane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(2-methylpyridin-3-yl)piperazine-1-carboxylate (2.67 g, 83 %) as a pale yellow oil. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=CC(=CC=C1)Br;amine:CC1=CC2=C(N1)C=C(C=C2)OC(F)(F)F, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];metal and ligand:CC(C)(C)P(C1=CC=CC=C1C2=CC=CC=C2)C(C)(C)C;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], and Products are 0:CC1=CC2=C(N1C3=CC(=CC=C3)OC)C=C(C=C2)OC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: EN04773-51, _Buchwald coupling,_ ** _J. Med. Chem. 2009, page 3846-3854 (exactly same reaction)._** The indole from 4773-41, 1-bromo-3-methoxybenzenee,Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 120 °C for 1h and ~65% conversion was observed on NMR*(see attached NMR). Reaction seems to work fine and assumed better yield than in 4773-50. This could be due to that bromides generally perform better than iodines in the Buchwald coupling. This test reaction was thrown away. |
Here is a chemical reaction formula: Reactants are:amine:C[C@@H]1CNC[C@@H](N1)C;aryl halide:C1=CC(=CC=C1Br)I, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:CC(C)(C)[O-].[Na+], and Products are 0:C[C@@H]1CN(C[C@@H](N1)C)C2=CC=C(C=C2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: sodium 2-methylpropan-2-olate (4.08 g, 42.42 mmol) was added to (2R,6S)-2,6-dimethylpiperazine (4.84 g, 42.42 mmol) in dioxane (300 mL) at 21°C under nitrogen. Stirred for 5 mins. 1-bromo-4-iodobenzene (8 g, 28.28 mmol) added, followed by diacetoxypalladium (0.635 g, 2.83 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (3.27 g, 5.66 mmol). Reaction evacuated and refilled with nitrogen several times. Heated at 90C for 18hours. Diluted with ethyl acetate and filtered through celite. The organic layer was washed with water ( 500ml) and then dried over Na2SO4, filtered and reduced in volume. Filtered - lcms messy. Dissolved in DCM and combined with the filtrate - adsorbed onto silica. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford (3S,5R)-1-(4-bromophenyl)-3,5-dimethylpiperazine (4.69 g, 61.6 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC=C1Br)I;amine:C[C@@H]1CNC[C@@H](N1)C, Reagents are:Solvent:C1COCCO1;Base:CC(C)(C)[O-].[Na+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C[C@@H]1CN(C[C@@H](N1)C)C2=CC=C(C=C2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: sodium 2-methylpropan-2-olate (0.510 g, 5.30 mmol) was added to (2R,6S)-2,6-dimethylpiperazine (0.605 g, 5.30 mmol) in dioxane (40 mL) at 21°C under nitrogen. Stirred for 5 mins. 1-bromo-4-iodobenzene (1 g, 3.53 mmol) added, followed by diacetoxypalladium (0.079 g, 0.35 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.409 g, 0.71 mmol). Reaction evacuated and refilled with nitrogen several times. Heated at 90C for 18hours. left to cool o/w. The reaction mixture was diluted with EtOAc (250 mL), and washed sequentially with water (150 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% MeOH in EtOAc. Pure fractions were evaporated to dryness to afford (3S,5R)-1-(4-bromophenyl)-3,5-dimethylpiperazine (0.420 g, 44.1 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC(=C(C(=C1)F)C2=CC=C(C=C2)Br)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C[C@H](CNC1=CC=C(C=C1)C2=C(C=CC=C2F)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: PdOAc2 (0.030 g, 0.13 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.064 g, 0.13 mmol) were added in one portion to a degassed solution of 4'-bromo-2,6-difluorobiphenyl (0.36 g, 1.34 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (0.355 g, 1.87 mmol) and cesium carbonate (0.654 g, 2.01 mmol) in toluene (10 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120 °C for 50 hours. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL) and the biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was evaporated to afford crude product. 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 (R)-N-(2-(tert-butyldimethylsilyloxy)propyl)-2',6'-difluorobiphenyl-4-amine (0.300 g, 59.4 %) as a yellow solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)F;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (0.020 g, 0.09 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (0.8g, 2.23 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.110 g, 0.19 mmol), 1-bromo-3,5-difluorobenzene (0.321 ml, 2.79 mmol) and cesium carbonate (1.091 g, 3.35 mmol) suspended in 1,4-dioxane (22.00 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 20 hours. _maybe not complete but have to go forward_ The reaction mixture was allowed to cool to room temperature, the insoluble were removed by filtration and the filtrate concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (0.760 g, 66.2 %) as a beige foam. |
Here is a chemical reaction formula: Reactants are:amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=C(C=C(C=C1F)Br)F, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.13 mg, 0.01 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (125 mg, 0.35 mmol), 1-bromo-3,5-difluorobenzene (0.044 ml, 0.38 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.15 mg, 0.03 mmol) and cesium carbonate (170 mg, 0.52 mmol) dissolved in 1,4-dioxane (2 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 10 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was quenched with water and extracted with dichloromethane (2 x 10 ml). The combined organic phases were dried over magnesium sulfate and concentrated to afford the crude product as a orange/yellow oil. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (118 mg, 71.9 %) as a yellow gum. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)F;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Solvent:C1COCCO1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (0.033 g, 0.15 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.326 g, 3.7 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.182 g, 0.31 mmol), 1-bromo-3,5-difluorobenzene (0.533 ml, 4.63 mmol) and cesium carbonate (1.808 g, 5.55 mmol) suspended in 1,4-dioxane (36 ml). The resulting suspension was degased with argon and then stirred at 100 °C over the WE (66hours). Albeit Lcms showed ~ 7% SM remaining, the reaction was stopped. The reaction mixture was allowed to cool to room temperature, the insolubles were removed by filtration and the filtrate concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 2 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1.172 g, 67.3 %) as a beige foam. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)F;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (6.26 mg, 0.03 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (200 mg, 0.56 mmol), 1-bromo-3,5-difluorobenzene (0.080 ml, 0.70 mmol) and cesium carbonate (273 mg, 0.84 mmol) dissolved in 1,4-dioxane (8 ml). The resulting suspension was degased with argon and then stirred at 100 °C (15:00) for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (137 mg, 52.2 %) as a clear yellow foam. LCMS and NMR are OK. |
Here is a chemical reaction formula: Reactants are:amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=C(C=C(C=C1F)Br)F, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (6.26 mg, 0.03 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (200 mg, 0.56 mmol), 1-bromo-3,5-difluorobenzene (0.080 ml, 0.70 mmol) and cesium carbonate (273 mg, 0.84 mmol) dissolved in 1,4-dioxane (8 ml). The resulting suspension was degased with argon and then stirred at 100 °C (18:00) for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (173 mg, 65.9 %) as a clear yellow foam. LCMS and NMR are OK. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)F;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (0.028 g, 0.13 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (0.9 g, 2.51 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.145 g, 0.25 mmol), 1-bromo-3,5-difluorobenzene (0.361 ml, 3.14 mmol) and cesium carbonate (1.227 g, 3.77 mmol) suspended in 1,4-dioxane (16.05 ml). The resulting suspension was degased with argon and then stirred at 100 °C (18:00) for 15 hours. The reaction mixture was allowed to cool to room temperature, concentrated in presence of silica gel and purified by flash chromatography on silica gel eluting with 0 to 10% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (0.792 g, 67.0 %) as an yellow foam. |
Here is a chemical reaction formula: Reactants are:amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=C(C=C(C=C1F)Br)F, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (0.439 g, 1.95 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (14 g, 39.06 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.260 g, 3.91 mmol), 1-bromo-3,5-difluorobenzene (5.62 ml, 48.83 mmol) and cesium carbonate (19.09 g, 58.60 mmol) suspended in 1,4-dioxane (250 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 16 hours. The reaction mixture was allowed to cool to room temperature, concentrated in presence of silica gel and purified by Chromatography on silica gel (Novasep) eluting with 0 to 10% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (10.30 g, 56.0 %) as an yellow foam. |
Here is a chemical reaction formula: Reactants are:amine:CC1=CC2=C(N1)C=C(C=C2)OC(F)(F)F;aryl halide:C1=CC=C(C=C1)COC2=CC(=CC=C2)I, Reagents are:metal and ligand:CC(C)(C)P(C1=CC=CC=C1C2=CC=CC=C2)C(C)(C)C;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];Base:CC(C)(C)[O-].[Na+];Solvent:C1COCCO1, and Products are 0:CC1=CC2=C(N1C3=CC(=CC=C3)OCC4=CC=CC=C4)C=C(C=C2)OC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: EN04773-50, _Buchwald coupling,_ ** _J. Med. Chem. 2009, page 3846-3854 (changed: solvent to dioxane and bromide to iodide)._** The indole from 4773-41, 1-(benzyloxy)-3-iodobenzene, Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 120 °C for 1h and ~40% conversion was observed on NMR. The reaction mixture was further heated at 80 °C for 16h and 40 h, see attached 1H-NMR for reaction progress. A comparison with 4773-51 shows that using dioxane or iodide gives a lower yield (slower reaction). Switching the solvent to toluene was explored in 4773-52. The reaction in this experiment showed that the Buchwald conditions worked. Reaction mixture was thrown away. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=CC(=CC=C2)I;amine:CC1=CC2=C(N1)C=C(C=C2)OC(F)(F)F, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)(C)P(C1=CC=CC=C1C2=CC=CC=C2)C(C)(C)C;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], and Products are 0:CC1=CC2=C(N1C3=CC(=CC=C3)OCC4=CC=CC=C4)C=C(C=C2)OC(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: EN04773-52, _Buchwald coupling, toluene and iodide_ The indole from 4773-25, 1-(benzyloxy)-3-iodobenzene,Pd2(dba)3, JohnPhos and KOtBu were dissolved in toluene. The mixture was warmed at 120 °C for 1h and 50% conversion was observed on NMR*(see attached NMR). The mixture was warmed further 15h at 120°C, still starting material left but the reaction mixture was directly applied to a silica column (heptane 3:1). Product was collected in fraction 22-23 (see attached NMR). Only 19.3 mg (10.45% yield) could be collected but NMR showed correct product. Test reaction with bromide was performed in 4773-53. ######################### *Small amount from reaction mixture was dissolved in CDCl3 and 1HNMR analysis was performed) |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=C1Br)C(F)(F)F;amine:CC(C)(C)OC(=O)N1C[C@@H]2C[C@H]1CN2, Reagents are:Solvent:C1COCCO1;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;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];Base:CC(C)(C)[O-].[Na+], and Products are 0:CC(C)(C)OC(=O)N1CC2CC1CN2C3=CN=CC(=C3)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 50 ml round bottom equipped with stir bar was charged with BINAP (225 mg, 0.36 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (138 mg, 0.15 mmol) dissolved in 1,4-dioxane (7.500 mL). This was degassed and purged with nitrogen and stirred at RT for 10 mins. 3-bromo-5-(trifluoromethyl)pyridine (340 mg, 1.50 mmol) followed by tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (597 mg, 3.01 mmol) and sodium tert-butoxide (578 mg, 6.02 mmol) were added, and the reaction was stirred at 80 °C for 2 hrs. The crude material was loaded on a Snap KP-SIL 100g column and purified on a Biotage Isolera One instrument, eluting with 10% to 35% ethyl acetate in heptane to provide tert-butyl 5-(5-(trifluoromethyl)pyridin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (425 mg, 82 %) as an oil. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=C1Br)C(F)(F)F;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Solvent:C1COCCO1;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;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];Base:CC(C)(C)[O-].[Na+], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CN=CC(=C2)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A 100 ml round bottom equipped with stir bar was charged with (S)-BINAP (331 mg, 0.53 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (203 mg, 0.22 mmol) dissolved in 1,4-dioxane (10.700 mL). This was degassed and purged with nitrogen and stirred at RT for 10 mins. 3-bromo-5-(trifluoromethyl)pyridine (500 mg, 2.21 mmol) followed by tert-butyl piperazine-1-carboxylate (824 mg, 4.42 mmol) and sodium tert-butoxide (850 mg, 8.85 mmol) were added, and the reaction was stirred at 80 °C for 2 hrs. The crude material was loaded on a Snap KP-SIL 100g column and purified on a Biotage Isolera One instrument, eluting with 10% to 30% ethyl acetate in heptane to provide tert-butyl 4-(5-(trifluoromethyl)pyridin-3-yl)piperazine-1-carboxylate (630 mg, 86 %) as an oil. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC=C1C#N)Br;amine:CCNCC, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC#N;Base:C(=O)([O-])[O-].[K+].[K+], and Products are 0:CCN(CC)C1=CC=C(C=C1)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-Bromobenzonitrile (2.000 g, 10.99 mmol), diethylamine (3.41 mL, 32.96 mmol) and POTASSIUM CARBONATE (4.56 g, 32.96 mmol) were mixed in dry acetonitrile (10 mL) under argon in a microwave vial. The vial was sealed and heated with microvawes for 60 minutes at 160°C. Added diethylamine (3.41 mL, 32.96 mmol) and heated at 160°C for 3 hours. Added Palladium(II) acetate (0.123 g, 0.55 mmol) and 2-(Dicyclohexylphosphino)-2',4',6'-tri-i- propyl-1,1'-biphenyl (0.524 g, 1.10 mmol), purged with argon for 5 minutes and heated in an oil bath at 100°C for 24 hours. The reaction was cooled to rt and partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (40 mL). The layers were separated and the aqueous phase extracted with EtOAc (100 mL). The organics were combined, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on silica gel gave 4-(diethylamino)benzonitrile (0.750 g, 39.2 %) |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=N1)Cl;amine:C1=CC(=CC(=C1)S(=O)(=O)N)N, Reagents are:Solvent:CC(=O)N(C)C;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1=CC(=CC(=C1)S(=O)(=O)N)NC2=NC=CN=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 3-aminobenzenesulfonamide (130mg, 0.75 mmol), 2-chloropyrazine (0.067 mL, 0.75 mmol),(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (34.9 mg, 0.06 mmol), diacetoxypalladium (6.78 mg, 0.03 mmol) and cesium carbonate (295 mg, 0.91 mmol) in degassed DMA (2.1 mL) was heated **_in the microwave_** for 15 min at 130 °C. LC MS FLA-04665-01-01 (pH extract 6-7) showed some product and few sulfanilamide left. Reaction was stopped. Extraction with AE + ethanol / aq. sat NH4Cl (pH7), then back extraction with DCM.The organics were dried over MgSO4 and concentrated _in vacuo._ The crude product was adsorbed on silica gel 40-60µm and purified by flash chromatography on silica gel 15-40µm eluting with 3.5 % of ethanol in dichloromethane (NH3 0.5 %) to provide 3-(pyrazin-2-ylamino)benzenesulfonamide (80 mg, 42.3 %) as a colourless solid. 1H NMR, LC MS FLA-04665-09-02: OK |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=N1)Br;amine:C1=CC(=CC(=C1)S(=O)(=O)N)N, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC(=O)N(C)C;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1=CC(=CC(=C1)S(=O)(=O)N)NC2=CN=CN=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 3-aminobenzenesulfonamide (110mg, 0.64 mmol), 5-bromopyrimidine (102 mg, 0.64 mmol),(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (29.6 mg, 0.05 mmol), diacetoxypalladium (5.74 mg, 0.03 mmol) and cesium carbonate (250 mg, 0.77 mmol) in degassed DMA (1.9 mL) was heated **_in the microwave_** for 35 min at 130°C. LC MS FLA-04665-12-01 (pH extract 6-7) showed some product. Reaction was stopped. Extraction with AE + ethanol / aq. sat NH4Cl (pH7), then back extraction with DCM.The organics were dried over MgSO4 and concentrated _in vacuo._ The crude product was adsorbed on silica gel 40-60µm and purified by flash chromatography on silica gel 15-40µm eluting with 3.5 % of ethanol in dichloromethane (NH3 0.5 %) to provide 3-(pyrimidin-5-ylamino)benzenesulfonamide (30.0 mg, 18.77 %) as a yellow solid. 1H NMR,LC MS: FLA-04665-12-02a: OK |
Here is a chemical reaction formula: Reactants are:amine:C1C[C@@H](C2=NC(=NN2C1)N)C3=CC=C(C=C3)F;aryl halide:C1=CC(=CC=C1CC#N)Br, Reagents are:Solvent:C1COCCO1;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1CC(C2=NC(=NN2C1)NC3=CC=C(C=C3)CC#N)C4=CC=C(C=C4)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (98 mg, 0.42 mmol), 2-(4-bromophenyl)acetonitrile (83 mg, 0.42 mmol), Cesium carbonate (206 mg, 0.63 mmol), Palladium(II) acetate (9.47 mg, 0.04 mmol) and 2-(Dicyclohexylphosphino)biphenyl (14.79 mg, 0.04 mmol) were added to a 2-5 mL microwave vial. The vial was capped and flushed with nitrogen. dioxane (2 mL) was added and the vial was flushed with additional nitrogen before it was heated by microwave irradiation at 120°C for 1.5h. PALLADIUM(II) ACETATE (10 mg, 0.04 mmol) and 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (14 mg, 0.04 mmol) were added and the mixture was heated for 45+30 min at 120° in a microwave reactor.Water (2 ml) and dichloromethane (10 ml) was added and the mixture was added to a phase separator tube. The organic phase was collected and evaporated. The solvents were evaporated and the residue was purified by column chromatography on silica eluting with gradients of methanol and ammonia in dichloromethane. The solvents were evaporated to give EN04671-48-001 (55 mg, 0.158 mmol, 37.5 %). Ca 88% pure according to LC-UV. The residue was dissolved in MeCN (2 ml) and the solution was passed through a syringe filter. Water was added to give a cloudy mixture (sample-002). Not possible to isolate solid by filtration. The solvents were evaporated to give EN04671-48-002. Not pure. EtOAc (2ml) and DCM (0.5 ml) and two drops of methanol were added. Most solid into solution. The mixture was passed through a syringe filter. The filter was rinsed with EtOAc (1 ml). Heptane was added until a solid started to form. The mixture was left for 1 h (sample -003). The mixture was filtered, everything passed through the filter. The solvents were evaporated and the residue was dissolved in MeCN and purified by preparative HPLC. Fr 1-2 were pooled and evaporated to give EN04671-48-004 (6.7 mg, 0.019 mmol, 4.57 %). Fr 3-6 were pooled and evaporated. |
Here is a chemical reaction formula: Reactants are:amine:CN1CCC[C@@H]1COC2=CN=C(C=C2)N;aryl halide:C1=CC=C2C(=C1)N=CN2C3=CC(=NC=N3)Cl, Reagents 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;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];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:CN1CCC[C@@H]1COC2=CN=C(C=C2)NC3=CC(=NC=N3)N4C=NC5=CC=CC=C54, please give me the reaction condition of this formula. | The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (31.6 mg, 0.03 mmol) was added to (R)-5-((1-methylpyrrolidin-2-yl)methoxy)pyridin-2-amine (143 mg, 0.69 mmol), 1-(6-chloropyrimidin-4-yl)-1H-benzo[d]imidazole (159 mg, 0.69 mmol), sodium t-butoxide (99 mg, 1.03 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (59.8 mg, 0.10 mmol) in toluene (6 mL) at 20°C under nitrogen. The resulting suspension was stirred at 100 °C for 16 hours then cooled to room temperature. LCMS analysis indicates no SM, product peak present. The reaction mixture was concentrated _in vacuo_. The residue was dissolved in DCM (100 mL) and washed with water (100 mL). The organic layer was passed through phase separating cartridge and concentrated under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford a yellow gum. 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 (R)-6-(1H-benzo[d]imidazol-1-yl)-N-(5-((1-methylpyrrolidin-2-yl)methoxy)pyridin-2-yl)pyrimidin-4-amine (39.0 mg, 14.09 %) as an pale yellow solid. Experiment was re-opened on 08/06/2012 to record additional data for publication. 13C and HRMS data recorded as separate sections rather than within sample details due to ELN conflict when trying to sign and close with redundant project code. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=CC(=CN=C1)Br;amine:C1CNCCC12OCCO2, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:COC1=CN=CC(=C1)N2CCC3(CC2)OCCO3, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 11/05 2011 07:58:54 +0200 A mixture of 3-bromo-5-methoxypyridine (1.5 g, 7.98 mmol), 1,4-dioxa-8-azaspiro[4.5]decane (1.023 ml, 7.98 mmol), palladium(II) acetate (0.107 g, 0.48 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.228 g, 0.48 mmol) in toluene (38.3 ml) and tBuOH (7.65 ml) was evacuated and flashed with N2 several times. Then sodium 2-methylpropan-2-olate (0.920 g, 9.57 mmol) was added and the reaction mixture was heated to 100°C for 2hrs. LCMS showed complete conversion. Reaction mixture had turned black. The reaction mixture was filtered through celite. The celite was washed with DCM. The combined filtrates were concentrated to yield 2.2g of brown oil, which starts to crystalise patially. Crude NMR showed only little unreacted amine (ca. 14%). The crude was purified by flash: The residue was purified by automated flash chromatography on a 100g column. A gradient from 40% to 100% of EA in Hep over 12CV, 100% EA over 6CV was used as mobile phase. The product was collected using the wavelength 254 nm. 1.5g of desired product were obtained as a light yellow oil. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CN=C1)Br;amine:C1=CC(=CN=C1)N, Reagents are:Solvent:COCCOC;metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:C1=CC(=CN=C1)NC2=CN=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Stock solution: 2.43 M solution of CyPF-tBu/Pd(OAc)2 (1:1) in DME. pyridin-3-amine (3.57 g, 37.98 mmol) was dissolved in DME (10 mL). To the mixture was added 10 mL of stock solution, and sodium tert-butoxide (4.26 g, 44.30 mmol). 5 min later, to the mixtue was added a solution of 3-bromopyridine (3.05 mL, 31.65 mmol) in DME (10 mL). The mixture was heated at 100 °C overnight. LCMS1 showed the result after 1 h heating. LCMS2 showed the result after 18 h heating, which showed the product formation, and the starting material 3-BrPy. LCMS3 showed the result after 40 h heating. LCMS4 was after 60h. To the mixture was added 50 mL DCM and acetic acid (2 mL, 34.94 mmol). The mixture was stirred for 10 min, and then was filtered. The filtrate was concentrated, and the compound was purified by preparative HPLC on a XBridge C18 column (10 µm 250x50 ID mm) using a gradient of 0-60% acetonitrile in H2O/ACN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. The compounds were detected by UV at 254nm (LCMS5). After freezing-dried overnight, product dipyridin-3-ylamine (0.540 g, 9.97 %) was obtained. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CN=C1)Br;amine:C1=CC(=CN=C1)N, Reagents are:metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC;Base:CC(C)(C)[O-].[Na+], and Products are 0:C1=CC(=CN=C1)NC2=CN=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Stock solution: 2.43 M solution of CyPF-tBu/Pd(OAc)2 (1:1) in DME. 3-bromopyridine (0.482 mL, 5.00 mmol) was dissolved in DME (10 mL). To the solution was added 2mL of stock solution, and sodium tert-butoxide (0.673 g, 7.00 mmol). To the mixture was added a solution of pyridin-3-amine (0.565 g, 6.00 mmol) in DME (10 mL). The mixture was heated at 90 °C overnight. LCMS showed the product formation, but the starting material 3-BrPy was still . To the mixture was added 2 mL stock solution additionally, and the mixture was heated at 90 °C for another 2h, but LCMS did not show improvement. The mixture was filtered. The filtrate was concentrated, and the compound was purified by preparative HPLC on a XBridge C18 column (10 µm 250x50 ID mm) using a gradient of 0-50% acetonitrile in H2O/ACN/NH3 95/5/0.2 buffer over 15 minutes with a flow of 100 mL/min. The compounds were detected by UV at 254nm. To the fractions (ca. 60mL) were added 5 mL of HOAc. The product was freezing-dried to give the product dipyridin-3-ylamine (0.031 g, 3.62 %). |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CN=C1)Br;amine:C1=CC(=CN=C1)N, Reagents are:Solvent:COCCOC;metal and ligand:CC(C1CCCC1P(C2CCCCC2)C3CCCCC3)P(C(C)(C)C)C(C)(C)C.C1CCCC1.[Fe];metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:C1=CC(=CN=C1)NC2=CN=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Stock solution: 2.43 M solution of CyPF-tBu/Pd(OAc)2 (1:1) in DME. 3-bromopyridine (6 mL, 62.28 mmol) was dissolved in DME (10 mL). To the solution was added 10 mL of stock solution, and sodium tert-butoxide (8.38 g, 87.19 mmol). To the mixture was added a solution of pyridin-3-amine (7.03 g, 74.74 mmol) in DME (10 mL). The mixture was heated at 100 °C overnight. LCMS showed the product formation, and the starting material 3-BrPy . To the mixture was added 4 mL stock solution additionally, and the mixture was heated at 100 °C for another 5h. LCMS showed more impurities peaks. The mixture was filtered. The filtrate was concentrated, and the compound was purified by preparative HPLC on a XBridge C18 column (10 µm 250x50 ID mm) using a gradient of 0-50% acetonitrile in H2O/ACN/NH3 95/5/0.2 buffer over 15 minutes with a flow of 100 mL/min. The compounds were detected by UV at 254nm. To the fractions (ca. 1000mL) were added 20 mL of HOAc. The product was freezing- dried to give the 1.56 g of product. But NMR1 showed that there was 5 eq. acetic acid in the crude. The residue was dissolved in 10 mL methanol. To the solution was added 10 mL of aq. ammonia solution, and the crude was freezing- dried overnight to give the product dipyridin-3-ylamine (1.300 g, 12.19 %) . |
Here is a chemical reaction formula: Reactants are:amine:C1C[C@@H](C2=NC(=NN2C1)N)C3=CC=C(C=C3)F;aryl halide:CN(C)C(=O)C1=CC=C(C=C1)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN(C)C(=O)C1=CC=C(C=C1)NC2=NN3CCCC(C3=N2)C4=CC=C(C=C4)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (101 mg, 0.43 mmol), 4-bromo-N,N-dimethylbenzamide (100 mg, 0.44 mmol), Cesium carbonate (211 mg, 0.65 mmol), Palladium(II) acetate (9.8 mg, 0.04 mmol) and 2-(Dicyclohexylphosphino)biphenyl (15.8 mg, 0.05 mmol) were added to a microwave vial. The vial was capped and flushed with nitrogen. Dioxane (2.5 mL) was added and the vial was flushed with additional nitrogen before it was irradiated in a microwave reactor at 120 °C for 1.5 h. The reaction mixture was diluted with dichloromethane and filtered through a pad of diatomaceous earth. The pad was rinced repeatedly with dichloromethane, then the solvents were removed _in vacuo_. Handed over to the preparative chromatography group for purification (see attached report). The desired fractions were pooled and concentrated _in vacuo_. The residue was partitioned between water and dichloromethane (x1), the organic layer was passed through a phase separator and concentrated _in vacuo_. The residue was redissolved in acetonitrile and water was added. Freeze-dried over weekend to give 4-(8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-N,N-dimethylbenzamide (67.5 mg, 40.9 %). |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)C#N;amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Solvent:C1COCCO1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)C#N)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.93 mg, 0.02 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (130 mg, 0.35 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.25 mg, 0.03 mmol), 3-bromo-5-fluorobenzonitrile (88 mg, 0.44 mmol) and cesium carbonate (171 mg, 0.52 mmol) dissolved in 1,4-dioxane (4 ml). The resulting suspension was degased with argon and then stirred at 100 °C (18:00) for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in V-10 Evaporator (Biotage) The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(3-cyano-5-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (90 mg, 52.4 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)Br;amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC=CC=C4)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.93 mg, 0.02 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (130 mg, 0.35 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.25 mg, 0.03 mmol), bromobenzene (0.046 ml, 0.44 mmol) and cesium carbonate (171 mg, 0.52 mmol) dissolved in 1,4-dioxane (4 ml). The resulting suspension was degased with argon and then stirred at 100 °C (18:00) for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in V-10 Evaporator (Biotage) The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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,N-dimethyl-2-morpholino-4-oxo-8-(1-phenylpyrrolidin-2-yl)-4H-chromene-6-carboxamide (59.0 mg, 37.7 %) as a solid. |
Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC=C1F)Br, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC=C(C=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (7.56 mg, 0.03 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (250 mg, 0.67 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (38.9 mg, 0.07 mmol), 1-bromo-4-fluorobenzene (0.092 ml, 0.84 mmol) and cesium carbonate (329 mg, 1.01 mmol) dissolved in 1,4-dioxane (5 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (47.0 mg, 15.00 %) as a solid. |
Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC=C1F)Br, Reagents are:Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC=C(C=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (0.756 mg, 3.37 µmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (25 mg, 0.07 mmol), [Reactants], 1-bromo-4-fluorobenzene (9.24 µl, 0.08 mmol) and cesium carbonate (32.9 mg, 0.10 mmol) dissolved in 1,4-dioxane (1.5 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (6.00 mg, 19.15 %) as a solid. |
Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC=C1F)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC=C(C=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (7.56 mg, 0.03 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (250 mg, 0.67 mmol), biphenyl-2-yldicyclohexylphosphine (23.59 mg, 0.07 mmol), 1-bromo-4-fluorobenzene (0.092 ml, 0.84 mmol) and cesium carbonate (329 mg, 1.01 mmol) dissolved in 1,4-dioxane (5 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was dissolved in DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (155 mg, 49.5 %) as a gum 200mg (155mg from EN05368-13 and 45mg from EN04870-97) was sent to the collection and purified by chiral separation. |
Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC=C1F)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC=C(C=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (1.511 mg, 6.73 µmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (50 mg, 0.13 mmol), biphenyl-2-yldicyclohexylphosphine (4.72 mg, 0.01 mmol), 1-bromo-4-fluorobenzene (0.018 ml, 0.17 mmol) and cesium carbonate (65.8 mg, 0.20 mmol) dissolved in 1,4-dioxane (1.5 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (10.00 mg, 15.96 %) as a gum. |
Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC=C1F)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC=C(C=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.93 mg, 0.02 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (130 mg, 0.35 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20.25 mg, 0.03 mmol), 1-bromo-4-fluorobenzene (0.048 ml, 0.44 mmol) and cesium carbonate (171 mg, 0.52 mmol) dissolved in 1,4-dioxane (4 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated in V-10 Evaporator (Biotage) The crude product was dissolved in 2ml of DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (31.0 mg, 19.03 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC(=C1N)Br)F;amine:CCOC(=O)CN.Cl, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:CCOC(=O)CNC1=C(C=C(C=N1)F)N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 50 mL round-bottomed flask 2-bromo-5-fluoropyridin-3-amine (500 mg, 2.62 mmol) ethyl 2-aminoacetate hydrochloride (731 mg, 5.24 mmol) BINAP (163 mg, 0.26 mmol) palladium(II) acetate (58.8 mg, 0.26 mmol) CESIUM CARBONATE (2559 mg, 7.85 mmol) were taken.The solids were mixed well and degassed.The toluene was taken in another RB and degassed using Nitrogen.The degassed toluene was then added to the solids.The resulting RM was heated to reflux for 16 hrs. The reaction was monitored by LCMS, which indicated starting material only and no required product. Therefore, the batch was discarded. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=N1)Cl;amine:CC(C1=CC=CC=C1)N, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(C1=CC=CC=C1)NC2=NC=CN=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 1-phenylethanamine (212 mg, 1.75 mmol) and 2-chloropyrazine (200 mg, 1.75 mmol) in toluene (10 mL) while bubbling N2 was added binap (141 mg, 0.23 mmol), sodium tert-butoxide (235 mg, 2.44 mmol) and palladium(II) acetate (51.0 mg, 0.23 mmol). The reaction mixure was heated at 70 oC for 3 hours. The reaction was concentrated, partitioned between ethyl acetate and water. The aqueous phase was extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was loaded on a 40g silica gel column and purified on a Teledyne Isco instrument, eluting with 20% to 70% ethyl acetate in heptane to provide N-(1-phenylethyl)pyrazin-2-amine (148 mg, 42.5 %) as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C;amine:CS(=O)(=O)C1=CC=C(C=C1)N, Reagents are:Solvent:CC(=O)N(C)C;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 10 mL microwave reactor 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (100 mg, 0.43 mmol) and 4-(methylsulfonyl)aniline (73.0 mg, 0.43 mmol) were dissolved in DMA (3 mL) to give a tan solution.To the resultant solution Cesium carbonate (0.068 mL, 0.85 mmol) was added and sparged with nitrogen for 1 minute. Then Palladium(II) acetate (6.70 mg, 0.03 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (29.6 mg, 0.05 mmol) were added and the reaction mixture was sealed. The reaction was heated to150 °C for 25 minutes in the biotage microwave.The reaction was cooled to room temperature and LCMS shows reaction was completed. Reaction mixture was filtered through Celite Bed and washed with Dichloromethane. Filtrate was subjected to concentration to get DMA solution which was given to analytical department to purify using Mass based HPLC. After purification compound was isolated to get pale yellow solid of 4-(2,6-dimethylpyridin-3-yloxy)-N-(4-(methylsulfonyl)phenyl)pyridin-2-amine (80 mg, 50.8 %) |
Here is a chemical reaction formula: Reactants are:amine:C1COCCN1CCNS(=O)(=O)C2=CC=C(C=C2)N;aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC(=O)N(C)C;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)NCCN4CCOCC4)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 10 mL microwave reactor 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (100 mg, 0.43 mmol) and 4-amino-N-(2-morpholinoethyl)benzenesulfonamide (122 mg, 0.43 mmol) were dissolved in DMA (5 mL) to give a tan solution.To the resultant solution Cesium carbonate (0.068 mL, 0.85 mmol) was added and sparged with nitrogen for 1 minute. Then Palladium(II) acetate (6.70 mg, 0.03 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (29.6 mg, 0.05 mmol) were added and the reaction mixture was sealed. The reaction was heated to150 °C for 25 minutes in the biotage microwave.The reaction was cooled to room temperature and LCMS shows reaction was completed. Reaction mixture was filtered through Celite Bed and washed with Dichloromethane. Filtrate was subjected to concentration to get DMA solution which was given to analytical department to purify using Mass based HPLC. After purification compound was isolated to get pale yellow solid of 4-(4-(2,6-dimethylpyridin-3-yloxy)pyridin-2-ylamino)-N-(2-morpholinoethyl)benzenesulfonamide (125 mg, 60.7 %) |
Here is a chemical reaction formula: Reactants are:amine:CC(COC)NS(=O)(=O)C1=CC=C(C=C1)N;aryl halide:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)Cl)C, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC(=O)N(C)C, and Products are 0:CC1=NC(=C(C=C1)OC2=CC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)NC(C)COC)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 10 mL microwave reactor 3-(2-chloropyridin-4-yloxy)-2,6-dimethylpyridine (100 mg, 0.43 mmol) and 4-amino-N-(1-methoxypropan-2-yl)benzenesulfonamide (104 mg, 0.43 mmol) were dissolved in DMA (3 mL) to give a brown solution.To the resultant solution Cesium carbonate (0.068 mL, 0.85 mmol) was added and sparged with nitrogen for 1 minute. Then Palladium(II) acetate (6.70 mg, 0.03 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (29.6 mg, 0.05 mmol) were added and the reaction mixture was sealed. The reaction was heated to150 °C for 25 minutes in the biotage microwave.The reaction was cooled to room temperature and LCMS shows reaction was completed. Reaction mixture was filtered through Celite Bed and washed with Dichloromethane. Filtrate was subjected to concentration to get DMA solution which was given to analytical department to purify using Mass based HPLC. After purification compound was isolated to get pale yellow solid of 4-(4-(2,6-dimethylpyridin-3-yloxy)pyridin-2-ylamino)-N-(1-methoxypropan-2-yl)benzenesulfonamide (98 mg, 52.0 %) |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=C(C=C1)I)Br;amine:C1COCCC1CN, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC1=C(C=C(C=C1)NCC2CCOCC2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium (II) acetate (0.032 g, 0.14 mmol) and racemic-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.179 g, 0.29 mmol) were suspended in toluene (3 mL). The mixture was evacuated and purged with nitrogen, and warmed to 50°C. In a separate vessel, 2-bromo-4-iodo-1-methoxybenzene (0.6 g, 1.92 mmol), (tetrahydro-2H-pyran-4-yl)methanamine (0.221 g, 1.92 mmol) and sodium-t- butoxide (0.276 g, 2.88 mmol) were suspended in toluene (3.5 mL). The resulting mixture was evacuated, purged with nitrogen and warmed to 50°C. After ~30 mins, the catalyst mixture was transferred to the reaction vessel. The reaction was evacuated and purged with nitrogen and heated at 80°C overnight. The mixture was filtered and purified by flash silica chromatography, elution 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford 3-bromo-4-methoxy-N-((tetrahydro-2H-pyran-4-yl)methyl)aniline (0.060 g, 10.42 %) as a brown solid. 60mg of product formed by LC-MS and major product is unknown but doesn't contain pyran signals in NMR and not SM iodide. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=C(C=C1)I)Br;amine:C1COCCC1CN, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:CC(C)(C)[O-].[Na+], and Products are 0:COC1=C(C=C(C=C1)NCC2CCOCC2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Palladium (II) acetate (0.075 g, 0.34 mmol) and racemic-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.223 g, 0.36 mmol) were suspended in dioxane (5mL). The mixture was evacuated and purged with nitrogen, and warmed to 50°C. In a separate vessel, 2-bromo-4-iodo-1-methoxybenzene (1.4 g, 4.47 mmol), (tetrahydro-2H-pyran-4-yl)methanamine (0.547 mL, 4.47 mmol) and sodium-t- butoxide (0.645 g, 6.71 mmol) were suspended in dioxane (5ML). The resulting mixture was evacuated, purged with nitrogen and warmed to 50°C. After ~30 mins, the catalyst mixture was transferred to the reaction vessel. The reaction was evacuated and purged with nitrogen and heated at 80°C overnight. Very little product and mainly SM so reaction abandoned. |
Here is a chemical reaction formula: Reactants are:amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=CC(=CC(=C1)Br)F, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC=C4)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (0.045 g, 0.20 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.8 g, 5.02 mmol), methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.8 g, 5.02 mmol) and cesium carbonate (2.455 g, 7.53 mmol) dissolved in 1,4-dioxane (35 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 11 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 20% methanol in ethyl acetate (on 50 min). The solvent was evaporated to dryness to afford methyl 8-(1-(3-fluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (1.610 g, 70.8 %) as a clear yellow foam. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=CC(=CC=C1)Br;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC1=CC=CC(=C1)N2CCCC2C3=CC(=CC4=C3OC(=CC4=O)N5CCOCC5)C(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (3.13 mg, 0.01 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (125 mg, 0.35 mmol), 1-bromo-3-methoxybenzene (0.049 ml, 0.38 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.15 mg, 0.03 mmol) and cesium carbonate (170 mg, 0.52 mmol) dissolved in 1,4-dioxane (2 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 11 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was quenched with water and extracted with dichloromethane (2 x 10 ml). The combined organic phases were dried over magnesium sulfate and concentrated to afford the crude product as a orange/yellow oil. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane. The solvent was evaporated to dryness to afford methyl 8-(1-(3-methoxyphenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (90 mg, 55.6 %) as a yellow gum. |
Here is a chemical reaction formula: Reactants are:amine:COC(=O)CN1CCNCC1;aryl halide:C1=CC(=CC=C1Br)Br, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;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], and Products are 0:COC(=O)CN1CCN(CC1)C2=CC=C(C=C2)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a reaction vial, 1,4-dibromobenzene (0.373 g, 1.58 mmol), methyl 2-(piperazin-1-yl)acetate (0.100 g, 0.63 mmol), CS2CO3 (0.309 g, 0.95 mmol), and BINAP (0.024 g, 0.04 mmol) were taken up in 1,4-dioxane (1.5 ml). Argon was bubbled through the solution for 1 minute. Pd2(dba)3 (0.012 g, 0.01 mmol) was added, followed by additional purging with argon. The vial was capped and placed on the heater-shaker. The reaction was stirred (450 rpm) at 100 °C overnight. LC/MS at this point did not indicate any formation of the dp. Experiment not progressed. |
Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C=CC(=C1)Br)F;amine:COC(=O)C1CCNCC1, Reagents are:Solvent:CC1=CC=CC=C1;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;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];Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=C(C=CC(=C1)N2CCC(CC2)C(=O)OC)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 100 mL round-bottomed flask methyl piperidine-4-carboxylate (2.2 g, 15.36 mmol),4-bromo-1-fluoro-2-methylbenzene (1.954 mL, 15.36 mmol),Pd2(dba)3 (0.521 g, 0.57 mmol),BINAP (0.574 g, 0.92 mmol) and sodium tert-butoxide (4.43 g, 46.09 mmol) was taken in toluene (10 mL) under N2.The resulting reaction was stirred at 110 °C for 3 hrs. LCMS did not show product MS.Material was discrded. |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC2=C(C1=O)C=C(C=C2)Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];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;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], and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC3=C(CN(C3=O)C)C=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In an oven-dried RB flask was added Tris(dibenzylideneacetone)dipalladium(0) (0.046 g, 0.05 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.062 g, 0.10 mmol). The flask was evacuated and back-filled with nitrogen. Anhydrous toluene (3 mL) was added and the mixture was stirred at rt for 10 min to give a purple solution. 6-bromo-2-methylisoindolin-1-one (2.261 g, 10 mmol), 1-Boc-piperazine (1.863 g, 10.00 mmol) and Sodium tert-butoxide (1.714 mL, 14.00 mmol) were added in one portion followed by anhydrous toluene (15 mL). The flask was evacuated and back-filled with nitrogen and the resulting mixture was stirred at 60 °C under a nitrogen atmosphere for 2 days. LCMS shows 10% conversion. Tris(dibenzylideneacetone)dipalladium(0) (0.183 g, 0.20 mmol) and 2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (0.187 g, 0.40 mmol) (RuPhos) were added and the mixture was heated to 80 °C and stirred for 5 h. LCMS shows complete conversion. When cooled to rt the mixture was diluted with EtOAc (25 mL) and stirred for 1 h. The solid was filtered off and washed with EtOAc (50 mL). The filtrate was washed with saturated aqueous Na2CO3 (20 mL), brine (20 mL), dried over MgSO4, filtered and concentrated. The crude producr was purified on a silica gel column eluted with 20-100% EtOAc in Heptane to give a yellow solid; tert-butyl 4-(2-methyl-3-oxoisoindolin-5-yl)piperazine-1-carboxylate (1.890 g, 57.0 %). |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=NC(=C1Br)Cl)Cl;amine:C1COCCN1, Reagents are:metal and ligand:CC(C)OC1=C(C(=CC=C1)OC(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;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];Solvent:CC(C)(C)O;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1COCCN1C2=C(N=C(C=C2)Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2011-05-18 r1 was checked by NMR and LC/MS: Vial a: 3-bromo-2,6-dichloropyridine (0.023 g, .1 mmol), morpholine (9.15 µl, 0.11 mmol), Pd2dba3 (1.831 mg, 2.00 µmol),4-(2,6-dichloropyridin-3-yl)morpholine (0.00 µg) were mixed in tBuOH (0.241 ml) in microwave vial. The vial was flushed with N2 and sealed and the mix was strd at rt. Vial b: As above, but in PhCF3. 1100:start 2011-05-19 0800: LC/MS: around 50% r1 in both vials. vial a: new peak at 1.53 min (20%), at 2.90 min (17%) and some small peaks as well. vial b: new peak at 1.54 min (32%), 2.61 min (25%) and at 2.90 min (5%) and some small peaks as well. MW/100 degr/20 min. LC/MS, pH3: vial a: 1.17 min: new peak (8-9%, not integrated); 2.11 min: new peak (31%), no right mass track. vial b: 1.17 min: new, small peak; 2.11 min: new peak (17%), no right mass track. The peak from the 2.11 peak is relatively higher in vial a than in b. ACS calculation: r1 has logD 3.60, product has logD 1.92. Any Br->H? Check of ret time of 2,6-diCl-pyridine (commercial ref. material): 1.86 min. NO such thing. at rt over night 2011-05-20 0800: LC/MS: around 50% r1 in both vials. MW/100 degr/20 min. LC/MS: vial a: 1.17 min (8%); 1.51 min (ca. 5%); 2.12 min (32%); 2.47 min (r1 peak; 38%) + other small peaks. vial b: 1.54 min (19%); 2.12 min (21%); 2.48 (24%); 2.90 min (11%). The crudes were mixed, concentrated and kept at rt over night. 2011-05-21 Passed thru Si-plug with MeOH. NMR on crude: very messy. Scrutiny of the arom. region did not show anything that seemed like the right product. Not taken further. |
Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:C1=CC(=NC(=C1Br)Cl)Cl, Reagents are:metal and ligand:CC(C)OC1=C(C(=CC=C1)OC(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;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];Base:CC(C)(C)[O-].[Na+];Solvent:C1CCOC1, and Products are 0:C1COCCN1C2=C(N=C(C=C2)Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: sodium tert-butoxide (0.012 g, 0.13 mmol), were transfered to a microwave vial. Pd2dba3 (0.916 mg, 1.00 µmol), dicyclohexyl(2',6'-diisopropoxybiphenyl-2-yl)phosphine (0.933 mg, 2.00 µmol), (2-DICYCLOHEXYLPHOSPHINO-2',6'-DIISOPROPYL-1,1'-BIPHENYL)[2-(2-AMINOETHYL)PHENYL]PALLADIUM(II) (0.729 mg, 1.00 µmol) were added. 3-bromo-2,6-dichloropyridine (0.011 g, .05 mmol) in tetrahydrofuran (0.474 ml) was added. The vial was flushed with N2, sealed, and the reaction mix was heated on an oil bath at 100 °C. 2011-10-05 0900: interrupted, cooled- LC/MS, 5 min method, pH11: 1H NMR on crude:not good spectra. 2011-10-06 The mix was filtered thru Si-plug and conc. 1H NMR and COSY. Very complex. Lower rection temp and time needed. Discarded. \---- Info from -25: 2011-09-18 Lit. ref: ....Buchwald, S. _Chem. Sci._ **2011** , _2_ , 57 sodium tert-butoxide (0.024 g, 0.25 mmol), were transfered to a microwave vial. Pd2dba3 (1.831 mg, 2.00 µmol),dicyclohexyl(2',6'-diisopropoxybiphenyl-2-yl)phosphine (1.867 mg, 4.00 µmol), (2-DICYCLOHEXYLPHOSPHINO-2',6'-DIISOPROPYL-1,1'-BIPHENYL)[2-(2-AMINOETHYL)PHENYL]PALLADIUM(II) (1.457 mg, 2.00 µmol) were added. [Reactants] in tetrahydrofuran (0.948 ml) was added. The vial was flushed with N2, sealed, and the reaction mix was heated on an oil bath at 100 °C. 2115: start 2011-09-19 0915: LC/MS, 5 min method, pH11: some r1 remained 3.62 major peak 1200: heating at 120 degr 2011-09-20 1400 lcms:5 min method, pH11: right mass peak appeared at 0.12 and 0.18 min.! seeemed very unlikely 4.20 still peak, probabaly r1 ,but difficult to say since no iionization This was a test experiment, starting from a mix of r1 and one monosubst. starting material. Repeated with pure r1, see -66. Report Cannot be finalized, since this program is useless. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=NC(=CC=C1)Br;amine:C1CNCCC12OCCO2, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:COC1=CC=CC(=N1)N2CCC3(CC2)OCCO3, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The same procedure as EN03653-93-01. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=CC(=CC(=C1)Br)Br;amine:C1=CC=C(C=C1)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC(=O)C1=CC(=CC(=C1)Br)NC2=CC=CC=C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: aniline (0.380 g, 4.08 mmol), methyl 3,5-dibromobenzoate (1.000 g, 3.40 mmol), Pd(OAc)2 (0.076 g, 0.34 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.295 g, 0.51 mmol) and CESIUM CARBONATE (1.663 g, 5.10 mmol) were stirred in toluene (10 mL) and degassed with nitrogen for 15 minutes. The mixture was then heated at 110 °C under nitrogen for 24 hours. No evidence of any significant amount of product (ester or acid) therfore abandaned. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=CC=C(C=C1)Br;amine:C1=C(C=C(C=C1F)F)CN, Reagents are:Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:COC(=O)C1=CC=C(C=C1)NCC2=CC(=CC(=C2)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: methyl 4-bromobenzoate (1 g, 4.65 mmol), (3,5-difluorophenyl)methanamine (1.100 mL, 9.30 mmol) and Cesium carbonate (1.515 g, 4.65 mmol) were mixed in toluene (4 mL) and degassed by bubbling nitrogen through solution. Palladium acetate (0.052 g, 0.23 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.203 g, 0.33 mmol) were added and the vial was capped and heated at 100°C over 5 days. Workup by dilution with EtOAc, washing with water, then extraction with 2M HCl. The HCl extract was neutralized with 2M NaOH and extracted with EtOAc and the EtOAc phase was dried (K2CO3) and evaporated to give the crude product. The identity of product was doubtful but it was already used in exp 60-68. |
Here is a chemical reaction formula: Reactants are:amine:C1=C(C=C(C=C1F)F)CN;aryl halide:COC(=O)C1=CC=C(C=C1)Br, Reagents are:Solvent:CC1=CC=CC=C1;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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC=C(C=C1)NCC2=CC(=CC(=C2)F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: methyl 4-bromobenzoate (1.8 g, 8.37 mmol), (3,5-difluorophenyl)methanamine (1.980 mL, 16.74 mmol) and Cesium carbonate (2.73 g, 8.37 mmol) were mixed in toluene (4 mL) and degassed by bubbling nitrogen through solution. Palladium acetate (0.094 g, 0.42 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.365 g, 0.59 mmol) were added and the vial was capped and heated at 100°C over 5 days. Workup by dilution with EtOAc, washing with water, then extraction with 2M HCl. The HCl extract was neutralized with 2M NaOH and extracted with EtOAc and the EtOAc phase was dried (K2CO3) and evaporated to give the crude product. The desired amine was not the compound isolated. Discarded. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=CC=C(C=C1)Br;amine:C1CNCC2=CC=CC=C21, Reagents 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;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:COC(=O)C1=CC=C(C=C1)N2CCC3=CC=CC=C3C2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: methyl 4-bromobenzoate (100 mg, 0.47 mmol), [Reactants] and Cesium carbonate (152 mg, 0.47 mmol) were mixed in toluene (4 mL) and degassed by bubbling nitrogen through solution. Palladium acetate (5.22 mg, 0.02 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (20.27 mg, 0.03 mmol) were added and the vial was capped and heated at 100°C over 5 days. Product had formed in mixture. Workup by dilution with EtOAc, washing with water, then extraction with 2M HCl. The HCl extract was neutralized with 2M NaOH and extracted with EtOAc and the EtOAc phase was dried (K2CO3) and evaporated to give the crude product. No product. Discarded. |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1=O)C=CC(=N2)Cl)C3=CC=CC=C3;amine:C1=CC(=CC=C1N)N2C=CN=C2, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1CC(OC2=C(C1=O)C=CC(=N2)NC3=CC=C(C=C3)N4C=CN=C4)C5=CC=CC=C5, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-chloro-4-methyl-2-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (115 mg, 0.40 mmol), 4-(1H-imidazol-1-yl)aniline (95 mg, 0.60 mmol), PdOAc2 (8.94 mg, 0.04 mmol), biphenyl-2-yldicyclohexylphosphine (13.96 mg, 0.04 mmol) and CS2CO3 (389 mg, 1.19 mmol) were placed in a microwave vial equipped with a stirring bar. The vial was capped and flushed with argon. DME (1.5 mL) was added via a syringe and the mixture was heated to 100°C in a microwave apparatus for 1 h. The residue was diluted with ethyl acetate and filtered through a short plug og Celite. The filtrate was evaporated and the residue was purified by HPLC to give 62 mg of the product as a solid. |
Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:CC1=C(C=CC=C1C(F)(F)F)CN2C(=NC3=C(C=C(C=C32)Br)C(=O)OC)C, Reagents are:metal and ligand:CCCCP(CCCC)CCCC;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1;Base:CC(C)(C)[O-].[K+], and Products are 0:CC1=C(C=CC=C1C(F)(F)F)CN2C(=NC3=C(C=C(C=C32)N4CCOCC4)C(=O)OC)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: methyl 6-bromo-2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazole-4-carboxylate (441 mg, 1.00 mmol) was taken up with morpholine (435 µl, 5.00 mmol), potassium tert-butoxide (449 mg, 4.00 mmol), tri-n-butylphosphine (49.3 µl, 0.2 mmol) and palladium(II) acetate (22.44 mg, 0.10 mmol) in dioxane (10ml) and heated for 18 hrs at 100°C. The reaction profile showed no required product and only dimer adduct to be present. the reaction was therefore abandoned. |
Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CC(=NC(=C1)Cl)C(F)(F)F, Reagents 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;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];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=CC=CC(=N2)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Objective: To test substrate scope in 5-ester substituted 2-aminooxazole coupling. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol), cesium carbonate (651 mg, 2.00 mmol), ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 2-chloro-6-(trifluoromethyl)pyridine (181 mg, 1.00 mmol) were placed in an oven dried microwave vial. The vial was then capped and placed under an inert atmosphere. Dioxane (4 mL) was added and the mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated the presence of the desired product. DCM (10 mL) was added to the crude reaction mixture together with C-18 silica (2 g), and the solvent was removed under reduced pressure. The solid residue was then placed in a dry-load tube prior to chromatography. The crude product was purified by reverse-phase flash chromatography on C-18 silica, elution gradient 30 to 80% MeCN in water (1% ammonium hydroxide). Pure fractions were evaporated to dryness to afford ethyl 2-(6-(trifluoromethyl)pyridin-2-ylamino)oxazole-5-carboxylate (204 mg, 67.8 %) as a beige solid. Conclusion: The desired product was isolated in moderate yield and high purity. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1C#N)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;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];Solvent:C1COCCO1, and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Objective: To test substrate scope in 5-ester substituted 2-aminooxazole coupling. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol), cesium carbonate (651 mg, 2.00 mmol), ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 2-chloroisonicotinonitrile (138 mg, 1.00 mmol) were placed in an oven dried microwave vial. The vial was then capped and placed under an inert atmosphere. Dioxane (4 mL) was added and the mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated the presence of the desired product as well as a significant amount of amine starting material. DCM (10 mL) was added to the crude reaction mixture together with C-18 silica (2 g), and the solvent was removed under reduced pressure. The solid residue was then placed in a dry-load tube prior to chromatography. The crude product was purified by reverse-phase flash chromatography on C-18 silica, elution gradient 20 to 60% MeCN in water (1% ammonium hydroxide). Pure fractions were evaporated to dryness to afford ethyl 2-(4-cyanopyridin-2-ylamino)oxazole-5-carboxylate (155 mg, 60.1 %) as a beige solid. Conclusion: The desired product was isolated in moderate yield. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=NC(=C1)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Solvent:C1COCCO1;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;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];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=CC=CC=N2, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Objective: To test the substrate scope in 5-ester substituted 2-aminooxazole coupling. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol), cesium carbonate (651 mg, 2.00 mmol), ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 2-chloropyridine (113 mg, 1.00 mmol) were placed in an oven dried microwave vial. The vial was then capped and placed under an inert atmosphere. Dioxane (4 mL) was added and the mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated the presence of the desired product. DCM (10 mL) was added to the crude reaction mixture together with C-18 silica (2 g), and the solvent was removed under reduced pressure. The solid residue was then placed in a dry-load tube prior to chromatography. The crude product was purified by reverse-phase flash chromatography on C-18 silica, elution gradient 10 to 60% MeCN in water (1% ammonium hydroxide). Pure fractions were evaporated to dryness to afford ethyl 2-(pyridin-2-ylamino)oxazole-5-carboxylate (88 mg, 37.8 %) as a beige solid. Conclusion: The desired product was isolated in moderate yield, but in only 84% purity based on LCMS. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=NC=C1[N+](=O)[O-])Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents 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;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];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=C(C=C2)[N+](=O)[O-], please give me the reaction condition of this formula. | The condition of this chemical reaction is: Objective: Test of substrate scope in couple of ester substituted aminooxazole To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol) 2-chloro-5-nitropyridine (158 mg, 1.00 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.07 mmol) and the vial was capped and purged with nitrogen. dioxane (4 mL) (degassed) was added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated that the desired product had been formed while only a trace of the amine starting material remained. DCM (20 mL) was added to the crude reaction mixture together with silica (2 g) and the solvent was removed under reduced pressure. The resulting residue was then placed in a dry-load tube prior to chromatography. The crude product was purified by flash silica chromatography, elution gradient 0 to 2.5% methanolic ammonia in DCM. Pure fractions were evaporated to dryness to afford ethyl 2-(5-nitropyridin-2-ylamino)oxazole-5-carboxylate (238 mg, 86 %) as a orange solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC=C1F)Br;amine:C1CC(NC1)C2=CC(=CC3=C2OC(=CC3=O)N4CCOCC4)C(=O)N5CCOCC5, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1CC(N(C1)C2=CC=C(C=C2)F)C3=CC(=CC4=C3OC(=CC4=O)N5CCOCC5)C(=O)N6CCOCC6, please give me the reaction condition of this formula. | The condition of this chemical reaction is: diacetoxypalladium (6.79 mg, 0.03 mmol) was added to a stirred mixture of 6-(morpholine-4-carbonyl)-2-morpholino-8-(pyrrolidin-2-yl)-4H-chromen-4-one (250 mg, 0.60 mmol), biphenyl-2-yldicyclohexylphosphine (21.19 mg, 0.06 mmol), 1-bromo-4-fluorobenzene (0.083 ml, 0.76 mmol) and cesium carbonate (296 mg, 0.91 mmol) dissolved in 1,4-dioxane (5 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 15 hours. The reaction mixture was allowed to cool to room temperature and concentrated. The crude product was dissolved in DMA. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 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 8-(1-(4-fluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (140 mg, 45.6 %) as a gum. The product was sent to the collection and purified by chiral separation by. |
Here is a chemical reaction formula: Reactants are:aryl halide:CCOC(=O)C1=CN=C(C=C1)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;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;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], and Products are 0:CCOC(=O)C1=CN=C(C=C1)NC2=NC=C(O2)C(=O)OCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Objective: Test of scope in the coupling of ester substituted aminooxazole To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol) and the vial was capped and purged with nitrogen. ethyl 6-chloronicotinate (185 mg, 1.00 mmol) and dioxane (4 mL) (degassed) were added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated that the desired product had formed with minimal formation of side-products. DCM (20 mL) was added to the crude reaction mixture together with silica (2 g). The solvent was removed under reduced pressure and the resulting residue was placed in a dry-load tube prior to chromatography. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% Methanolic ammonia in DCM. Pure fractions were evaporated to dryness to afford the desired product (270 mg, 88% isolated yield in 86% purity). This solid was triturated with hot MeCN and allowed to cool to room temperature to give a solid which was collected by filtration and dried under vacuum to give ethyl 2-(5-(ethoxycarbonyl)pyridin-2-ylamino)oxazole-5-carboxylate (205 mg, 67.2 %) as a cream solid. Conclusion: The desired product was isolated in moderate yield and high purity. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(N=C(C=N1)Cl)C#N;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Solvent:C1COCCO1;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;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];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC(=CN=C2)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Objective: Test of scope in the coupling of ester substituted aminooxazole To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), 6-chloropyrazine-2-carbonitrile (139 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol) and the vial was capped and purged with nitrogen. dioxane (4 mL) (degassed) was added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. DCM (20 mL) was added to the crude reaction mixture together with silica (2 g) and the solvent was removed under reduced pressure. The resulting residue was added to a dry-load tube prior to chromatography.The crude product was purified by flash silica chromatography, elution gradient 0 to 1% methanolic ammonia in DCM.. Pure fractions were evaporated to dryness to afford ethyl 2-(6-cyanopyrazin-2-ylamino)oxazole-5-carboxylate (121 mg, 46.7 %) as a cream solid. Conclusion: The desired product was formed in moderate yield purity. |
Here is a chemical reaction formula: Reactants are:amine:CC1=NC=CN1C2=CC=C(C=C2)N;aryl halide:CN1CC(OC2=C(C1=O)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC, and Products are 0:CC1=NC=CN1C2=CC=C(C=C2)NC3=NC4=C(C=C3)C(=O)N(CC(O4)C5=CC=CC=C5)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 8-chloro-4-methyl-2-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (173 mg, 0.60 mmol), 4-(2-methyl-1H-imidazol-1-yl)aniline (125 mg, 0.72 mmol), PdOAc2 (13.47 mg, 0.06 mmol), biphenyl-2-yldicyclohexylphosphine (21.03 mg, 0.06 mmol) and cesium carbonate (489 mg, 1.50 mmol) were placed in a microwave vial equipped with a stirring bar. The vial was capped, DME (4 mL) was added, the vial was flushed with nitrogen via a syringe and the mixture was heated to 100°C in a microwave reactor for 1 h. The residue was diluted with CH2Cl2 and filtered through a short plug of Celite. The filtrate was evaporated and the residue was purified by ISCO column chromatography on silica (gradient elution 0-6% methanol in dichloromethane) to give 4-methyl-8-(4-(2-methyl-1H-imidazol-1-yl)phenylamino)-2-phenyl-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (105 mg, 41.1 %). 68 mg given to Per Svensson crystallography. |
Here is a chemical reaction formula: Reactants are:amine:CC1=NC=CN1C2=CC=C(C=C2)N;aryl halide:CN1CC(OC2=C(C1=O)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC1=NC=CN1C2=CC=C(C=C2)NC3=NC4=C(C=C3)C(=O)N(CC(O4)C5=CC=CC=C5)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: were placed in a microwave vial equipped with a stirring bar. The vial was capped and flushed with argon. DME (2 mL) was added via a syringe and the mixture was heated to 100°C in a microwave apparatus for 1h. The reaction mixture was filtered, the solvent was evaporated and the residue was purified by HPLC to give 53 mg (42 % yield) of the product as a solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1=O)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CC1=NC=CN1C2=CC=C(C=C2)N, Reagents are:metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CC1=NC=CN1C2=CC=C(C=C2)NC3=NC4=C(C=C3)C(=O)N(CC(O4)C5=CC=CC=C5)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Not continued. |
Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=CC(=C1)F)C2=NC(=NC=C2F)Cl;amine:CS(=O)(=O)CC1=CC(=CC=C1)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];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;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];Solvent:C1COCCO1, and Products are 0:COC1=C(C=CC(=C1)F)C2=NC(=NC=C2F)NC3=CC=CC(=C3)CS(=O)(=O)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 2-chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine (0.25 g, 0.97 mmol), 3-((methylsulfonyl)methyl)aniline (0.180 g, 0.97 mmol), cesium carbonate (1.270 g, 3.90 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.141 g, 0.24 mmol)and Pd2(dba)3 (0.178 g, 0.19 mmol) were suspended in degassed 1,4-dioxane (3 mL) at ambient temperature. The resulting mixture was degassed, purged with nitrogen and heated at 100 °C for 3 hours after which time reaction was shown to be complete by LC-MS. The mixture was allowed to cool overnight. The reaction mixture was diluted with water (250 mL), and extracted with DCM (250 mL). The organic was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution 50% ethyl acetate in Heptane. 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, 50 mm diameter, 150 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 5-fluoro-4-(4-fluoro-2-methoxyphenyl)-N-(3-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine (0.200 g, 50.6 %) as a white solid. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=NC=C1Br)CO;amine:C1COCCN1, Reagents 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;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];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1COCCN1C2=CN=C(C=C2)CO, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a 10 mL Microwave vial was (5-bromopyridin-2-yl)methanol (500 mg, 2.66 mmol), morpholine (0.233 mL, 2.66 mmol),cesium carbonate (2166 mg, 6.65 mmol), Pd2(dba)3 (60.9 mg, 0.07 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (115 mg, 0.20 mmol) in dioxane (10 mL) () to give a brown suspension. The reaction mixture was heated to 110 °C for 3h. The reaction mixture was passed over Celite and washed with ethylacetate. The Filtrate was concentrate to dryness to get as a syrupy brown liquid. Water 30ml was added and extracted with ethylacetate (20x 2)ml. THe organic layers are collected, dried over Sodium Sulphate and concentrated to get as a liquid. The crude product was added to a silica gel column and was eluted with ethylacetate 0-70% Pure Collected fractions are evaporated to get as a (5-morpholinopyridin-2-yl)methanol (100 mg, 19.36 %)colorless liquid . The compound was carried to next step. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1F)C(F)(F)F)Br;amine:C[C@@H]1CNCCN1, Reagents 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;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];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:C[C@@H]1CN(CCN1)C2=C(C=C(C=C2)F)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-bromo-4-fluoro-2-(trifluoromethyl)benzene (5 g, 20.58 mmol), (R)-2-methylpiperazine (2.164 g, 21.61 mmol), sodium tert-butoxide (3.95 g, 41.15 mmol) and BINAP (0.512 g, 0.82 mmol) in anhydrous toluene (60 mL) was degassed under vacuum with inlet of nitrogen. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.377 g, 0.41 mmol) was added, the mixture again degassed. The resulting suspension was stirred at 100 °C for 6 hours under nitrogen. LCMS: Product formed. Cooled and evaporated. Residue diluted with diethyl ether (75 mL), filtered through Celite and the filtrates extracted with 2M HCl (2x30 mL). The combined aqueous layers were basified with solid NaOH to pH ~10, extracted with diethyl ether (2x50 mL), the organic extracts washed with water (2x10 mL) and brine, dried over mgSO4, filtered and evaporated to give crude product (3.2g, 59%) as an orange oil which was used without further purification. |
Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1F)C(F)(F)F)Br;amine:C[C@@H]1CNCCN1, Reagents are:Solvent:CC1=CC=CC=C1;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;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];Base:CC(C)(C)[O-].[Na+], and Products are 0:C[C@@H]1CN(CCN1)C2=C(C=C(C=C2)F)C(F)(F)F, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-bromo-4-fluoro-2-(trifluoromethyl)benzene (10 g, 41.15 mmol), (R)-2-methylpiperazine (4.33 g, 43.21 mmol), sodium tert-butoxide (7.91 g, 82.31 mmol) and BINAP (1.025 g, 1.65 mmol) in anhydrous toluene (100 mL) was degassed under vacuum with inlet of nitrogen. TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.754 g, 0.82 mmol) was added, the mixture again degassed. The resulting suspension was stirred at 100 °C for 4 hours under nitrogen. LCMS: Product formed. Heated for a further 2 hours. LCMS: Reaction complete. Cooled and evaporated. Residue diluted with diethyl ether (75 mL), filtered through Celite and the filtrates extracted with 2M HCl (2x30 mL). The combined aqueous layers were basified with solid NaOH to pH ~10, extracted with diethyl ether (2x50 mL), the organic extracts washed with water (2x10 mL) and brine, dried over MgSO4, filtered and evaporated to give crude product (3.2g, 59%) as an orange oil which was used without further purification. |