2-(2,4-difluorophenyl)acetyl 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: To a mixture of 2,4-difluorophenylacetic acid (206 mg), DMF (1 drop) and tetrahydrofuran (4 ml) was added oxalyl chloride (0.13 ml) dropwise. The resulting mixture was stirred at room temperature for 1 hour and the solvent was then distilled off to give 2,4-difluorophenylacetyl chloride. This chloride was dissolved in dichloromethane (5 ml) followed by addition of 3-amino-4-(2-chlorophenyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (294 mg) and N,N-dimethylaniline (0.13 ml). The mixture was further stirred at room temperature for 3 hours, after which it was washed with water, saturated aqueous solution of NaHCO3 and water in the order mentioned and dried (over MgSO4). The solvent was then distiled off to give 4-(2-chlorophenyl)-3-(2,4-difluorophenylacetylamino)-7,8-dihydro-6H-cyclopenta(g)quinoline as oil. This oil was crystallized from isopropyl ether (yield 342 mg, 76.3%). Recrystallization from ethanol gave colorless prisms, mp. 179°-180° C. the solvent was then distilled off

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

実験手順: To a mixture of 2,4-difluorophenylacetic acid (206 mg), DMF (1 drop) and tetrahydrofuran (4 ml) was added oxalyl chloride (0.13 ml) dropwise. The resulting mixture was stirred at room temperature for 1 hour and the solvent was then distilled off to give 2,4-difluorophenylacetyl chloride. This chloride was dissolved in dichloromethane (5 ml) followed by addition of 3-amino-4-(2-chlorophenyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (294 mg) and N,N-dimethylaniline (0.13 ml). The mixture was further stirred at room temperature for 3 hours, after which it was washed with water, saturated aqueous solution of NaHCO3 and water in the order mentioned and dried (over MgSO4). The solvent was then distiled off to give 4-(2-chlorophenyl)-3-(2,4-difluorophenylacetylamino)-7,8-dihydro-6H-cyclopenta(g)quinoline as oil. This oil was crystallized from isopropyl ether (yield 342 mg, 76.3%). Recrystallization from ethanol gave colorless prisms, mp. 179°-180° C. the solvent was then distilled off

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

実験手順: A solution of 2,4-difluorophenylacetyl chloride (10 mmol) in dry DCM (15 ml) was added over 10 min. to a mixture of t-butyl carbazate (1.32 g, 10 mmol) and DIPEA (1.77 ml, 10.2 mmol) in dry DCM (20 ml). After stirring for 1.5 h the mixture was washed with 1M HCl then with aqueous NaHCO3. The organic phase was evaporated to afford 1,1-dimethylethyl 2-[(2,4-difluorophenyl)acetyl]hydrazinecarboxylate as a white solid. was washed with 1M HCl The organic phase was evaporated

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

実験手順: To a mixture of 2,4-difluorophenylacetic acid (206 mg), DMF (1 drop) and tetrahydrofuran (4 ml) was added oxalyl chloride (0.13 ml) dropwise. The resulting mixture was stirred at room temperature for 1 hour and the solvent was then distilled off to give 2,4-difluorophenylacetyl chloride. This chloride was dissolved in dichloromethane (5 ml) followed by addition of 3-amino-4-(2-chlorophenyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (294 mg) and N,N-dimethylaniline (0.13 ml). The mixture was further stirred at room temperature for 3 hours, after which it was washed with water, saturated aqueous solution of NaHCO3 and water in the order mentioned and dried (over MgSO4). The solvent was then distiled off to give 4-(2-chlorophenyl)-3-(2,4-difluorophenylacetylamino)-7,8-dihydro-6H-cyclopenta(g)quinoline as oil. This oil was crystallized from isopropyl ether (yield 342 mg, 76.3%). Recrystallization from ethanol gave colorless prisms, mp. 179°-180° C. the solvent was then distilled off

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

実験手順: To a solution of 2-ethoxy-3-[3-(2-heptylamino-ethyl)-phenyl]-propionic acid methyl ester HCl salt (43 mg, 0.11 mmol) and N,N-diisopropylethylamine (0.33 mmol, 0.058 mL) in anhydrous methylene chloride (2 mL) was added 2,4-difluorophenylacetyl chloride (0.128 mmol) in anhydrous methylene chloride (2 mL). The mixture was allowed to stir at room temperature for 16 hours. Then was poured over 1 M HCl (5 mL). The aqueous layer was isolated and extracted with methylene chloride (1×). The organic layers were combined, washed with 2 M HCl (1×), brine (1×), dried over anhydrous sodium sulfate, and concentrated to give a clear oil. The crude product was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 20% ethyl acetate/hexanes to give 3-[4-(2-{[(2,4-difluoro-phenyl)-acetyl]-heptyl-amino}-ethyl)-phenyl]-2-ethoxy-propionic acid methyl ester as a clear oil (36.5 mg, 66%). The aqueous layer was isolated extracted with methylene chloride (1×) washed with 2 M HCl (1×), brine (1×) dried over anhydrous sodium sulfate concentrated to give a clear oil The crude product was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 20% ethyl acetate/hexanes

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

実験手順: To a mixture of 2,4-difluorophenylacetic acid (206 mg), DMF (1 drop) and tetrahydrofuran (4 ml) was added oxalyl chloride (0.13 ml) dropwise. The resulting mixture was stirred at room temperature for 1 hour and the solvent was then distilled off to give 2,4-difluorophenylacetyl chloride. This chloride was dissolved in dichloromethane (5 ml) followed by addition of 3-amino-4-(2-chlorophenyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (294 mg) and N,N-dimethylaniline (0.13 ml). The mixture was further stirred at room temperature for 3 hours, after which it was washed with water, saturated aqueous solution of NaHCO3 and water in the order mentioned and dried (over MgSO4). The solvent was then distilled off to give 4-(2-chlorophenyl)-3-(2,4-difluorophenylacetylamino)-7,8-dihydro-6H-cyclopenta(g)quinoline as oil. This oil was crystallized from isopropyl ether (yield 342 mg, 76.3%). Recrystallization from ethanol gave colorless prisms, mp. 179°-180° C. the solvent was then distilled off

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: To a solution of 2-ethoxy-3-[3-(2-heptylamino-ethyl)-phenyl]-propionic acid methyl ester HCl salt (43 mg, 0.11 mmol) and N,N-diisopropylethylamine (0.33 mmol, 0.058 mL) in anhydrous methylene chloride (2 mL) was added 2,4-difluorophenylacetyl chloride (0.128 mmol) in anhydrous methylene chloride (2 mL). The mixture was allowed to stir at room temperature for 16 hours. Then was poured over 1 M HCl (5 mL). The aqueous layer was isolated and extracted with methylene chloride (1×). The organic layers were combined, washed with 2 M HCl (1×), brine (1×), dried over anhydrous sodium sulfate, and concentrated to give a clear oil. The crude product was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 20% ethyl acetate/hexanes to give 3-[4-(2-{[(2,4-difluoro-phenyl)-acetyl]-heptyl-amino}-ethyl)-phenyl]-2-ethoxy-propionic acid methyl ester as a clear oil (36.5 mg, 66%). The aqueous layer was isolated extracted with methylene chloride (1×) washed with 2 M HCl (1×), brine (1×) dried over anhydrous sodium sulfate concentrated to give a clear oil The crude product was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 20% ethyl acetate/hexanes

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

実験手順: To a mixture of 2,4-difluorophenylacetic acid (206 mg), DMF (1 drop) and tetrahydrofuran (4 ml) was added oxalyl chloride (0.13 ml) dropwise. The resulting mixture was stirred at room temperature for 1 hour and the solvent was then distilled off to give 2,4-difluorophenylacetyl chloride. This chloride was dissolved in dichloromethane (5 ml) followed by addition of 3-amino-4-(2-chlorophenyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (294 mg) and N,N-dimethylaniline (0.13 ml). The mixture was further stirred at room temperature for 3 hours, after which it was washed with water, saturated aqueous solution of NaHCO3 and water in the order mentioned and dried (over MgSO4). The solvent was then distilled off to give 4-(2-chlorophenyl)-3-(2,4-difluorophenylacetylamino)-7,8-dihydro-6H-cyclopenta(g)quinoline as oil. This oil was crystallized from isopropyl ether (yield 342 mg, 76.3%). Recrystallization from ethanol gave colorless prisms, mp. 179°-180° C. the solvent was then distilled off

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

実験手順: A solution of 2,4-difluorophenylacetyl chloride (10 mmol) in dry DCM (15 ml) was added over 10 min. to a mixture of t-butyl carbazate (1.32 g, 10 mmol) and DIPEA (1.77 ml, 10.2 mmol) in dry DCM (20 ml). After stirring for 1.5 h the mixture was washed with 1M HCl then with aqueous NaHCO3. The organic phase was evaporated to afford 1,1-dimethylethyl 2-[(2,4-difluorophenyl)acetyl]hydrazinecarboxylate as a white solid. was washed with 1M HCl The organic phase was evaporated

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

実験手順: To a mixture of 2,4-difluorophenylacetic acid (206 mg), DMF (1 drop) and tetrahydrofuran (4 ml) was added oxalyl chloride (0.13 ml) dropwise. The resulting mixture was stirred at room temperature for 1 hour and the solvent was then distilled off to give 2,4-difluorophenylacetyl chloride. This chloride was dissolved in dichloromethane (5 ml) followed by addition of 3-amino-4-(2-chlorophenyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (294 mg) and N,N-dimethylaniline (0.13 ml). The mixture was further stirred at room temperature for 3 hours, after which it was washed with water, saturated aqueous solution of NaHCO3 and water in the order mentioned and dried (over MgSO4). The solvent was then distiled off to give 4-(2-chlorophenyl)-3-(2,4-difluorophenylacetylamino)-7,8-dihydro-6H-cyclopenta(g)quinoline as oil. This oil was crystallized from isopropyl ether (yield 342 mg, 76.3%). Recrystallization from ethanol gave colorless prisms, mp. 179°-180° C. the solvent was then distilled off