[2-(difluoromethoxy)phenyl]methanamine

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

実験手順: A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.578 mmol), 2-(difluoromethoxy)benzylamine (110 mg, 0.636 mmol), Pd2(dba)3 (47 mg, 0.051 mmol), rac-BINAP (108 mg, 0.173 mmol) and NaOtBu (139 mg, 1.445 mmol) in DMA (5 mL) was heated at 85° C. for 2 h. The mixture was allowed to cool, diluted with EtOAc and washed with water. The organic layer was washed with sat.aq. NaHCO3, brine and dried (Na2SO4). Chromatography on silica (EtOAc/hexanes) afforded 4-chloro-6-(2-difluoromethoxy-benzylamino)-2H-phthalazin-1-one (14 mg) as a yellow solid, 1H (400 MHz, d6-DMSO) δ: 4.43 (d, 2H), 6.81 (s, 1H), 7.14 (dd, 1H), 7.22 (m, 2H), 7.27 (t, 1H), 7.37 (m, 2H), 7.60 (t, 1H), 7.93 (d, 1H), 12.35 (s, 1H) ppm; m/z (M+1) 351.92. to cool washed with water The organic layer was washed with sat.aq NaHCO3, brine and dried (Na2SO4)

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

実験手順: The title compound was prepared by the same method as 4-{3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester starting from 3-bromo-5-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbamoyl-propoxy)-phenyl]-hexyloxy}-benzoic acid (900 mg, 1.48 mmol), PyBroP (828 mg, 1.77 mmol), 2-(difluoromethoxy)-benzylamine (306 mg, 1.77 mmol) and DIPEA (515 uL, 2.96 mmol) in dichloromethane (30 mL) to obtain 4-[3-{6-[3-bromo-5-(2-difluoromethoxy-benzylcarbamoyl)-phenoxy]-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (960 mg, 85%) as a colorless oil

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

実験手順: A mixture 6-bromo-4-chloro-2H-phthalazin-1-one (150 mg, 0.578 mmol), 2-(difluoromethoxy)benzylamine (110 mg, 0.636 mmol), Pd2(dba)3 (47 mg, 0.051 mmol), rac-BINAP (108 mg, 0.173 mmol) and NaOtBu (139 mg, 1.445 mmol) in DMA (5 mL) was heated at 85° C. for 2 h. The mixture was allowed to cool, diluted with EtOAc and washed with water. The organic layer was washed with sat.aq. NaHCO3, brine and dried (Na2SO4). Chromatography on silica (EtOAc/hexanes) afforded 4-chloro-6-(2-difluoromethoxy-benzylamino)-2H-phthalazin-1-one (14 mg) as a yellow solid, 1H (400 MHz, d6-DMSO) δ: 4.43 (d, 2H), 6.81 (s, 1H), 7.14 (dd, 1H), 7.22 (m, 2H), 7.27 (t, 1H), 7.37 (m, 2H), 7.60 (t, 1H), 7.93 (d, 1H), 12.35 (s, 1H) ppm; m/z (M+1) 351.92. to cool washed with water The organic layer was washed with sat.aq NaHCO3, brine and dried (Na2SO4)