非洛地平杂质N5

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ammonia (0.5 ml, d=0.88) was added to a solution of methyl alpha-(2,3-dichlorophenylmethylene)-beta-oxobenzenepropanoate (2 g, 7.3 mmoles) and ethyl 3-amino-2-butenoate (0.77 g, 6.0 mmoles) in tert. butanol (8 ml) at 60°. The reaction was maintained at this temperature for 16 hours. The solvent was removed in vacuo and the residue was chromatographed on silica eluting with ethyl acetate/petroleum ether (60°-80°) mixtures. The title compound (0.25 g) was obtained after crystallisation from 2-propanol mp 185°-6°. The reaction was maintained at this temperature for 16 hours The solvent was removed in vacuo the residue was chromatographed on silica eluting with ethyl acetate/petroleum ether (60°-80°)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl 4,4,4-trichloro-2-(3-nitrophenylmethylene)-3-oxobutanoate (7.19 g, 0.02 mmoles) and ethyl 3-amino-2-butenoate (2.53 g) were heated at 60° for 24 hours in tert-butanol (60 ml). The solvent was evaporated and the residue chromatographed on silica eluting with ether/petroleum ether (60°-80°) mixtures to give the title compound (4.04 g). Recrystallised from 2-propanol. mp 125°-6.5°. The solvent was evaporated the residue chromatographed on silica eluting with ether/petroleum ether (60°-80°)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-Nitrobenzaldehyde (3.0 g, 20 mmoles), ethyl 3-amino-2-butenoate (2.6 g, 20 mmoles) and ethyl 4,4,4-trifluoro-3-oxobutanoate (2.92 ml, 20 mmoles) were heated at reflux in ethanol (25 ml) for 6 hours. The solvent was removed in vacuo and the residue crystallised by the addition of ether/petroleum ether (60°-80°). The resulting solid was recrystallised from ether/petroleum ether (60°-80°) to give the title compound as colourless crystals (1.9 g) mp 120°-1°. The solvent was removed in vacuo the residue crystallised by the addition of ether/petroleum ether (60°-80°) The resulting solid was recrystallised from ether/petroleum ether (60°-80°)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (E)-3-Phenyl-2-propenal (13.8 ml, 0.11 mol) and ethyl 3-amino-2-butenoate (12.9 g, 0.1 mol) were dissolved in 150 ml of absolute ethanol containing 0.5 ml of piperidine. The mixture was heated under reflux for 18 hours followed by removal of the solvent under vacuum to yield 17.6 g of ethyl 1,4-dihydro-2-methyl-4-phenyl-3-pyridinecarboxylate as a brown viscous oil. The mixture was heated under reflux for 18 hours followed by removal of the solvent under vacuum

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 22 L vessel fitted with a mechanical stirrer and distillation head was charged 2.5 L (16.47 mol) diethyl malonate followed by 4.0 L diphenyl ether. Agitation was started and 1.12 Kg (16.47 mol, 1 eq) of sodium ethoxide was added via a powder funnel. The mixture was gradually, heated to 160° C. and the liberated ethanol was removed via distillation, approximately 950 mL. After 30 min, ethanol distillation ceased and 2.127 Kg (16.47 mol, 1 eq) of 3-amino-but-2-enoic acid ethyl ester was added, and the resulting ethanol formed removed via distillation. After 30 minutes the mechanical stirrer could no longer stir the foamy mass. At this point, external heating was ceased and the mixture allowed to cool to ambient temperature. To the mixture was charged 4 L of methyl-tert-butyl ether (MTBE) and the granular solid broken up with a spatula. The solid was filtered and washed with MTBE. To the solid was then added 100 mL of conc. HCl and 2 L of chloroform to solublize the mixture. The mixture was then taken up three times in 4 L chloroform, and decanted into a 20 L bucket. The combined organic phases were dried over sodium sulfate. The mixture was concentrated in vacuo to afford an orange gummy mass, which was triturated with MTBE and filtered, washing the filter cake with MTBE. The resulting solid was recrystallized from ethanol to afford the desired product as pinkish needles. In a 22 L vessel fitted with a mechanical stirrer distillation head the liberated ethanol was removed via distillation, approximately 950 mL ethanol distillation removed via distillation At this point, external heating to cool to ambient temperature To the mixture was charged 4 L of methyl-tert-butyl ether (MTBE) The solid was filtered washed with MTBE To the solid was then added 100 mL of conc. HCl and 2 L of chloroform decanted into a 20 L bucket The combined organic phases were dried over sodium sulfate The mixture was concentrated in vacuo to afford an orange gummy mass, which was triturated with MTBE filtered washing the filter cake with MTBE The resulting solid was recrystallized from ethanol

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 22 L vessel fitted with a mechanical stirrer and distillation head was charged 2.5 L (16.47 mol) diethyl malonate followed by 4.0 L diphenyl ether. Agitation was started and 1.12 Kg (16.47 mol, 1 eq) of sodium ethoxide was added via a powder funnel. The mixture was gradually, heated to 160° C. and the liberated ethanol was removed via distillation, approximately 950 mL. After 30 min, ethanol distillation ceased and 2.127 Kg (16.47 mol, 1 eq) of 3-amino-but-2-enoic acid ethyl ester was added, and the resulting ethanol formed removed via distillation. After 30 minutes the mechanical stirrer could no longer stir the foamy mass. At this point, external heating was ceased and the mixture allowed to cool to ambient temperature. To the mixture was charged 4 L of methyl-tert-butyl ether (MTBE) and the granular solid broken up with a spatula. The solid was filtered and washed with MTBE. To the solid was then added 100 mL of conc. HCl and 2 L of chloroform to solublize the mixture. The mixture was then taken up three times in 4 L chloroform, and decanted into a 20 L bucket. The combined organic phases were dried over sodium sulfate. The mixture was concentrated in vacuo to afford an orange gummy mass, which was triturated with MTBE and filtered, washing the filter cake with MTBE. The resulting solid was recrystallized from ethanol to afford the desired product as pinkish needles. In a 22 L vessel fitted with a mechanical stirrer distillation head the liberated ethanol was removed via distillation, approximately 950 mL ethanol distillation removed via distillation At this point, external heating to cool to ambient temperature To the mixture was charged 4 L of methyl-tert-butyl ether (MTBE) The solid was filtered washed with MTBE To the solid was then added 100 mL of conc. HCl and 2 L of chloroform decanted into a 20 L bucket The combined organic phases were dried over sodium sulfate The mixture was concentrated in vacuo to afford an orange gummy mass, which was triturated with MTBE filtered washing the filter cake with MTBE The resulting solid was recrystallized from ethanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ammonia (0.5 ml, d=0.88) was added to a solution of methyl alpha-(2,3-dichlorophenylmethylene)-beta-oxobenzenepropanoate (2 g, 7.3 mmoles) and ethyl 3-amino-2-butenoate (0.77 g, 6.0 mmoles) in tert. butanol (8 ml) at 60°. The reaction was maintained at this temperature for 16 hours. The solvent was removed in vacuo and the residue was chromatographed on silica eluting with ethyl acetate/petroleum ether (60°-80°) mixtures. The title compound (0.25 g) was obtained after crystallisation from 2-propanol mp 185°-6°. The reaction was maintained at this temperature for 16 hours The solvent was removed in vacuo the residue was chromatographed on silica eluting with ethyl acetate/petroleum ether (60°-80°)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl 4,4,4-trichloro-2-(3-nitrophenylmethylene)-3-oxobutanoate (7.19 g, 0.02 mmoles) and ethyl 3-amino-2-butenoate (2.53 g) were heated at 60° for 24 hours in tert-butanol (60 ml). The solvent was evaporated and the residue chromatographed on silica eluting with ether/petroleum ether (60°-80°) mixtures to give the title compound (4.04 g). Recrystallised from 2-propanol. mp 125°-6.5°. The solvent was evaporated the residue chromatographed on silica eluting with ether/petroleum ether (60°-80°)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-Nitrobenzaldehyde (3.0 g, 20 mmoles), ethyl 3-amino-2-butenoate (2.6 g, 20 mmoles) and ethyl 4,4,4-trifluoro-3-oxobutanoate (2.92 ml, 20 mmoles) were heated at reflux in ethanol (25 ml) for 6 hours. The solvent was removed in vacuo and the residue crystallised by the addition of ether/petroleum ether (60°-80°). The resulting solid was recrystallised from ether/petroleum ether (60°-80°) to give the title compound as colourless crystals (1.9 g) mp 120°-1°. The solvent was removed in vacuo the residue crystallised by the addition of ether/petroleum ether (60°-80°) The resulting solid was recrystallised from ether/petroleum ether (60°-80°)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (E)-3-Phenyl-2-propenal (13.8 ml, 0.11 mol) and ethyl 3-amino-2-butenoate (12.9 g, 0.1 mol) were dissolved in 150 ml of absolute ethanol containing 0.5 ml of piperidine. The mixture was heated under reflux for 18 hours followed by removal of the solvent under vacuum to yield 17.6 g of ethyl 1,4-dihydro-2-methyl-4-phenyl-3-pyridinecarboxylate as a brown viscous oil. The mixture was heated under reflux for 18 hours followed by removal of the solvent under vacuum