cyclohex-3-ene-1-carbonyl chloride

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 mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C. washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2SO4 added to the filtrate at the boil

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

実験手順: A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C. washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4 added to the filtrate at the boil

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

実験手順: Triethylamine (10 ml.) was added with stirring to a solution of 5.5 g. (±)-trans-1,2,3,4,4a,8,9,14a-octahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine in 100 ml. chloroform, followed by addition, with stirring, of 5.76 g. (0.04 moles) 3-cyclohexene-1-carbonyl chloride in 10 ml. chloroform. The mixture was refluxed 2 hours then cooled and water was added. The organic layer was separated, dried over K2CO3, and evaporated to dryness in vacuo. Trituration of the residual oil in hexane gave (±)-trans-3-[(3-cyclohexen-1-yl)carbonyl]-1,2,3,4,4a,8,9,14a-octahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine, m.p. 156.5°-158.5° . with stirring, of 5.76 g The mixture was refluxed 2 hours then cooled The organic layer was separated dried over K2CO3 evaporated to dryness in vacuo

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

実験手順: A solution of the starting (R)-[1-methyl-2-(4-thiophen-2-yl-3,6-dihydro-2H-pyrid-1-yl)-ethyl]-pyrid-2-yl-amine (0.46 g, 1.5 mmol) in methylene chloride (20 ml) was cooled to 0° C., after which a solution of cyclohex-3-enecarbonyl chloride (0.222 g, 1.5 mmol) in methylene chloride (10 ml) was dropwise added under exclusion of moisture. The reaction mixture was stirred at ambient temperature overnight, then washed with 2.5N NaOH (10 ml). The separated organic layer was washed with brine (50 ml), dried over magnesium sulfate, filtered, and evaporated to dryness in vacuo. Column chromatography on 50 g of silica gel with chloroform as eluant, followed by trituration in ether with the addition of ethanolic HCl gave 0.27g of the title compound as the dihydrochloride, m.p. 92°-6° C. washed with 2.5N NaOH (10 ml) The separated organic layer was washed with brine (50 ml) dried over magnesium sulfate filtered evaporated to dryness in vacuo Column chromatography on 50 g of silica gel with chloroform as eluant, followed by trituration in ether with the addition of ethanolic HCl

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

実験手順: A solution of the starting (R)-[1-methyl-2-(4-thiophen-2-yl-3,6-dihydro-2H-pyrid-1-yl)-ethyl]-pyrid-2-yl-amine (0.46 g, 1.5 mmol) in methylene chloride (20 ml) was cooled to 0° C., after which a solution of cyclohex-3-enecarbonyl chloride (0.222 g, 1.5 mmol) in methylene chloride (10 ml) was dropwise added under exclusion of moisture. The reaction mixture was stirred at ambient temperature overnight, then washed with 2.5N NaOH (10 ml). The separated organic layer was washed with brine (50 ml), dried over magnesium sulfate, filtered, and evaporated to dryness in vacuo. Column chromatography on 50 g of silica gel with chloroform as eluant, followed by trituration in ether with the addition of ethanolic HCl gave 0.27g of the title compound as the dihydrochloride, m.p. 92°-6° C. washed with 2.5N NaOH (10 ml) The separated organic layer was washed with brine (50 ml) dried over magnesium sulfate filtered evaporated to dryness in vacuo Column chromatography on 50 g of silica gel with chloroform as eluant, followed by trituration in ether with the addition of ethanolic HCl

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

実験手順: A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C. washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4 added to the filtrate at the boil

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

実験手順: The 4-hydroxy group of 4-hydroxybenzoic acid is protected by reacting 4-hydroxybenzoic acid, 5 g (0.036 mol), obtained commercially, with benzyl chloride, 5.1 g (0.04 mol) in ethanol:water (1:1) containing 5 g K2CO3 (0.04 mol) at a temperature of 30 degrees C. for 12 hours. The 4-PgO benzoic acid is converted to the acid chloride using thionyl chloride by a procedure similar to that employed for producing 3-cyclohexene carboxylic acid chloride from 3-cyclohexene carboxylic acid in Example I.

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

実験手順: An acid chloride was prepared as follows: anhydrous 3-cyclohexenecarboxylic acid (50 g, 0.4 mol) was placed in a 500 mL round-bottom flask and a few drops of N,N-dimethylformamide was added as a catalyst. To this was added dropwise thionyl chloride (58.4 mL, 0.8 mol), diluted with anhydrous toluene (50 mL), at room temperature and the reaction mixture was refluxed for 4 hours. The final product was fractionally distilled to yield 48.8 grams of 3-cyclohexenecarboxylic acid chloride at a yield of 85%. the reaction mixture was refluxed for 4 hours The final product was fractionally distilled

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

実験手順: A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C. washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2SO4 added to the filtrate at the boil

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

実験手順: A mixture of 208 mg of 3-cyclohexene-1-carbonyl chloride (prepared from 3-cyclohexene-1-carboxylic acid and thionyl chloride) and 145 mg of triethylamine in 3 ml of methylene chloride is added to a solution of 377 mg of 5-(4-aminobenzoyl)-6,11-dihydro-5H-dibenz[b,e]azepine in 7 ml of methylene chloride. The mixture is stirred for 18 hours, washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4. The organic layer is passed through a short column of hydrous magnesium silicate and hexane added to the filtrate at the boil to give 340 mg of the desired product as a crystalline solid, m.p. 234°-236° C. washed with water, 1N HCl, water, 1M NaHCO3 and brine then dried with Na2 SO4 added to the filtrate at the boil

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

実験手順: Triethylamine (10 ml.) was added with stirring to a solution of 5.5 g. (±)-trans-1,2,3,4,4a,8,9,14a-octahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine in 100 ml. chloroform, followed by addition, with stirring, of 5.76 g. (0.04 moles) 3-cyclohexene-1-carbonyl chloride in 10 ml. chloroform. The mixture was refluxed 2 hours then cooled and water was added. The organic layer was separated, dried over K2CO3, and evaporated to dryness in vacuo. Trituration of the residual oil in hexane gave (±)-trans-3-[(3-cyclohexen-1-yl)carbonyl]-1,2,3,4,4a,8,9,14a-octahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine, m.p. 156.5°-158.5° . with stirring, of 5.76 g The mixture was refluxed 2 hours then cooled The organic layer was separated dried over K2CO3 evaporated to dryness in vacuo