diethyl 2-(2-cyanoethyl)propanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(2-cyanoethyl)malonic acid diethyl ester (24.2 g) in tetrahydrofuran (15 ml) was added to a suspension of sodium hydride (2.45 g) in tetrahydrofuran (30 ml) at 20° C. under nitrogen. To this was added 2-chloro-3-nitro-5-bromopyridine (22 g) and the mixture so obtained was heated to 93°-95° C. A small amount of tetrahydrofuran was allowed to distil off. The mixture was heated under reflux for 2.5 hr. The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid. The aqueous phase was extracted with chloroform, dried (MgSO4) decolourised with charcoal and filtered through a silica column. The chloroform eluant was evaporated to yield an oil which slowly crystallised. The crystals were washed in petroleum ether (40°-60° C.) and dried to yield 4-(5-bromo-3-nitropyrid-2-yl)-4,4-bis(carbethoxy)butyronitrile (28 g) m.p. 58°-62° C. the mixture so obtained was heated to 93°-95° C to distil off The mixture was heated under reflux for 2.5 hr The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid The aqueous phase was extracted with chloroform dried (MgSO4) filtered through a silica column The chloroform eluant was evaporated to yield an oil which slowly crystallised The crystals were washed in petroleum ether (40°-60° C.) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(2-Cyanoethyl)malonic acid diethylester (40 g) was reacted with sodium hydride (4.4 gm) in tetrahydrofuran at 20° C. 2-Chloro-5-methyl-3-nitro-pyridine (35 g) was added and the internal temperature was raised to 100° C. (some tetrahydrofuran distilled off) over 4.25 hrs. The reaction mixture was partitioned between chloroform and water and treated with charcoal. Vacuum distillation of the chloroform extract and then chromatography (CHCl3, silica column) of the distillation residues gave 4-(5-methyl-3-nitropyrid-2-yl)-4,4-bis (carbethoxy)-butyronitrile (24.5 g) as a yellow solid m.p. 48°-49° C. distilled off) over 4.25 hrs The reaction mixture was partitioned between chloroform and water treated with charcoal Vacuum distillation of the chloroform extract

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(2-cyanoethyl)malonic acid diethyl ester (24.2 g) in tetrahydrofuran (15 ml) was added to a suspension of sodium hydride (2.45 g) in tetrahydrofuran (30 ml) at 20° C. under nitrogen. To this was added 2-chloro-3-nitro-5-bromopyridine (22 g) and the mixture so obtained was heated to 93°-95° C. A small amount of tetrahydrofuran was allowed to distil off. The mixture was heated under reflux for 2.5 hr. The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid. The aqueous phase was extracted with chloroform, dried (MgSO4) decolourised with charcoal and filtered through a silica column. The chloroform eluant was evaporated to yield an oil which slowly crystallised. The crystals were washed in petroleum ether (40°-60° C.) and dried to yield 4-(5-bromo-3-nitropyrid-2-yl)-4,4-bis(carbethoxy)butyronitrile (28 g) m.p. 58°-62° C. the mixture so obtained was heated to 93°-95° C to distil off The mixture was heated under reflux for 2.5 hr The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid The aqueous phase was extracted with chloroform dried (MgSO4) filtered through a silica column The chloroform eluant was evaporated to yield an oil which slowly crystallised The crystals were washed in petroleum ether (40°-60° C.) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4,4-Dicarbethoxybutyronitrile (1.2 g)and palladium-on-charcoal (0.6 g) are successively added to 5-methoxytryptamine (693 mg) dissolved in acetic acid. The mixture is stirred under a hydrogen atmosphere for 48 h. The medium is then filtered and the palladium is washed with a chloroform/methanol mixture. After evaporation of the solvent, the crude product obtained, dissolved in toluene, is refluxed overnight. The ethyl 9-methoxy-4-oxo-1,2,3,4,6,7,12,12b-octahydropyrido[2,1 -a]-(3-carboline-3-carboxylate precipitates and is recovered by simple filtration (35% yield). The medium is then filtered the palladium is washed with a chloroform/methanol mixture After evaporation of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4,4-Dicarbethoxybutyronitrile (1.2 g)and palladium-on-charcoal (0.6 g) are successively added to 5-methoxytryptamine (693 mg) dissolved in acetic acid. The mixture is stirred under a hydrogen atmosphere for 48 h. The medium is then filtered and the palladium is washed with a chloroform/methanol mixture. After evaporation of the solvent, the crude product obtained, dissolved in toluene, is refluxed overnight. The ethyl 9-methoxy-4-oxo-1,2,3,4,6,7,12,12b-octahydropyrido[2,1 -a]-(3-carboline-3-carboxylate precipitates and is recovered by simple filtration (35% yield). The medium is then filtered the palladium is washed with a chloroform/methanol mixture After evaporation of the solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(2-cyanoethyl)malonic acid diethyl ester (24.2 g) in tetrahydrofuran (15 ml) was added to a suspension of sodium hydride (2.45 g) in tetrahydrofuran (30 ml) at 20° C. under nitrogen. To this was added 2-chloro-3-nitro-5-bromopyridine (22 g) and the mixture so obtained was heated to 93°-95° C. A small amount of tetrahydrofuran was allowed to distil off. The mixture was heated under reflux for 2.5 hr. The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid. The aqueous phase was extracted with chloroform, dried (MgSO4) decolourised with charcoal and filtered through a silica column. The chloroform eluant was evaporated to yield an oil which slowly crystallised. The crystals were washed in petroleum ether (40°-60° C.) and dried to yield 4-(5-bromo-3-nitropyrid-2-yl)-4,4-bis(carbethoxy)butyronitrile (28 g) m.p. 58°-62° C. the mixture so obtained was heated to 93°-95° C to distil off The mixture was heated under reflux for 2.5 hr The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid The aqueous phase was extracted with chloroform dried (MgSO4) filtered through a silica column The chloroform eluant was evaporated to yield an oil which slowly crystallised The crystals were washed in petroleum ether (40°-60° C.) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(2-cyanoethyl)malonic acid diethyl ester (24.2 g) in tetrahydrofuran (15 ml) was added to a suspension of sodium hydride (2.45 g) in tetrahydrofuran (30 ml) at 20° C. under nitrogen. To this was added 2-chloro-3-nitro-5-bromopyridine (22 g) and the mixture so obtained was heated to 93°-95° C. A small amount of tetrahydrofuran was allowed to distil off. The mixture was heated under reflux for 2.5 hr. The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid. The aqueous phase was extracted with chloroform, dried (MgSO4) decolourised with charcoal and filtered through a silica column. The chloroform eluant was evaporated to yield an oil which slowly crystallised. The crystals were washed in petroleum ether (40°-60° C.) and dried to yield 4-(5-bromo-3-nitropyrid-2-yl)-4,4-bis(carbethoxy)butyronitrile (28 g) m.p. 58°-62° C. the mixture so obtained was heated to 93°-95° C to distil off The mixture was heated under reflux for 2.5 hr The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid The aqueous phase was extracted with chloroform dried (MgSO4) filtered through a silica column The chloroform eluant was evaporated to yield an oil which slowly crystallised The crystals were washed in petroleum ether (40°-60° C.) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(2-cyanoethyl)malonic acid diethyl ester (24.2 g) in tetrahydrofuran (15 ml) was added to a suspension of sodium hydride (2.45 g) in tetrahydrofuran (30 ml) at 20° C. under nitrogen. To this was added 2-chloro-3-nitro-5-bromopyridine (22 g) and the mixture so obtained was heated to 93°-95° C. A small amount of tetrahydrofuran was allowed to distil off. The mixture was heated under reflux for 2.5 hr. The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid. The aqueous phase was extracted with chloroform, dried (MgSO4) decolourised with charcoal and filtered through a silica column. The chloroform eluant was evaporated to yield an oil which slowly crystallised. The crystals were washed in petroleum ether (40°-60° C.) and dried to yield 4-(5-bromo-3-nitropyrid-2-yl)-4,4-bis(carbethoxy)butyronitrile (28 g) m.p. 58°-62° C. the mixture so obtained was heated to 93°-95° C to distil off The mixture was heated under reflux for 2.5 hr The reaction mixture was poured into water and neutralised to pH 7 with concentrated hydrochloric acid The aqueous phase was extracted with chloroform dried (MgSO4) filtered through a silica column The chloroform eluant was evaporated to yield an oil which slowly crystallised The crystals were washed in petroleum ether (40°-60° C.) dried