(2-ethoxycarbonylphenyl)boronic acid

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trifluoro-methanesulfonic acid 9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester 46 (33.5 mg, 0.05 mmol) dissolved in toluene (3 mL)/ethanol (0.6 mL)/water (0.4 mL) was added K2CO3 (22 mg, 0.15 mmol), (2-ethoxycarbonylphenyl)boronic acid (22 mg, 0.10 mmol) and tetrakis-(triphenylphosphine)-palladium(0)(12.5 mg, 0.01 mmol). The reaction mixture in the flask was flashed with argon three times. It was then heated to 120° C. under argon 3 hours. The reaction was monitored by TLC (EtOAc/hexane 3/7) (Rf 46=0.6, Rf 281=0.5) and LC/MS. After cooling to room temperature, the mixture was diluted with EtOAc (20 mL) and washed with 1N HCl, saturated NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (3/7) to afford pure 2-[9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl]-benzoic acid ethyl ester 281, 9 mg, 26.8%. After cooling to room temperature washed with 1N HCl, saturated NaHCO3 and brine The organic phase was dried (MgSO4) filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (3/7)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trifluoro-methanesulfonic acid 9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester 46 (33.5 mg, 0.05 mmol) dissolved in toluene (3 mL)/ethanol (0.6 mL)/water (0.4 mL) was added K2CO3 (22 mg, 0.15 mmol), (2-ethoxycarbonylphenyl)boronic acid (22 mg, 0.10 mmol) and tetrakis-(triphenylphosphine)-palladium(0)(12.5 mg, 0.01 mmol). The reaction mixture in the flask was flashed with argon three times. It was then heated to 120° C. under argon 3 hours. The reaction was monitored by TLC (EtOAc/hexane 3/7) (Rf 46=0.6, Rf 281=0.5) and LC/MS. After cooling to room temperature, the mixture was diluted with EtOAc (20 mL) and washed with 1N HCl, saturated NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (3/7) to afford pure 2-[9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl]-benzoic acid ethyl ester 281, 9 mg, 26.8%. After cooling to room temperature washed with 1N HCl, saturated NaHCO3 and brine The organic phase was dried (MgSO4) filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (3/7)

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

実験手順: The title compound was synthesized in the same manner as in Example 272 from methyl 3-[4-[(3-bromobenzyl)oxy]phenyl]propanoate and 2-ethoxycarbonylphenylboronic acid. colorless oil (yield 12%).

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

実験手順: The title compound was synthesized in the same manner as in Example 272 from methyl 3-[4-[(3-bromobenzyl)oxy]phenyl]propanoate and 2-ethoxycarbonylphenylboronic acid. colorless oil (yield 12%).

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

実験手順: The title compound was synthesized in the same manner as in Example 272 from methyl 3-[4-[(3-bromobenzyl)oxy]phenyl]propanoate and 2-ethoxycarbonylphenylboronic acid. colorless oil (yield 12%).

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

実験手順: 6′-Formyl-3′-hydroxy-2′,4′-dimethoxy-biphenyl-2-carboxylic acid ethyl ester was prepared from 4-acetoxy-2-bromo-3,5-dimethoxybenzaldehyde (Example 162, step a) and 2-ethoxycarbonylphenyl boronic acid using the protocol described in Example 147, step a. Mass Spectrum: 331 (M+1).

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

実験手順: 6′-Formyl-3′-hydroxy-2′,4′-dimethoxy-biphenyl-2-carboxylic acid ethyl ester was prepared from 4-acetoxy-2-bromo-3,5-dimethoxybenzaldehyde (Example 162, step a) and 2-ethoxycarbonylphenyl boronic acid using the protocol described in Example 147, step a. Mass Spectrum: 331 (M+1).

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-(ethoxycarbonyl)phenylboronic acid (7.0 g, 39 mmol), 2-bromo-5-fluoroaniline (7.4 g, 39 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos, 0.32 g, 0.78 mmol), sodium acetate (4.1 g, 39 mmol), and palladium acetate (0.087 g, 0.39 mmol) in 18 ml. of ethanol was heated with stirring at 80° C. for 18 h. Additional 2-(ethoxycarbonyl)phenylboronic acid (2.0 g), S-Phos (0.095 g), palladium acetate (0.020 g), and sodium carbonate (1.2 g) was added and the mixture was stirred for 18 h. The solvent was removed by evaporation under reduced pressure, and the resulting solid was isolated by vacuum filtration, washing the remaining solid with water and then hexane. The remaining solid and dried in vacuo @50° C. to provide the title compound (4.39 g, 53% yield) which was used without further purification. the mixture was stirred for 18 h The solvent was removed by evaporation under reduced pressure the resulting solid was isolated by vacuum filtration washing the remaining solid with water The remaining solid and dried in vacuo @50° C.

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trifluoro-methanesulfonic acid 9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester 46 (33.5 mg, 0.05 mmol) dissolved in toluene (3 mL)/ethanol (0.6 mL)/water (0.4 mL) was added K2CO3 (22 mg, 0.15 mmol), (2-ethoxycarbonylphenyl)boronic acid (22 mg, 0.10 mmol) and tetrakis-(triphenylphosphine)-palladium(0)(12.5 mg, 0.01 mmol). The reaction mixture in the flask was flashed with argon three times. It was then heated to 120° C. under argon 3 hours. The reaction was monitored by TLC (EtOAc/hexane 3/7) (Rf 46=0.6, Rf 281=0.5) and LC/MS. After cooling to room temperature, the mixture was diluted with EtOAc (20 mL) and washed with 1N HCl, saturated NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (3/7) to afford pure 2-[9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl]-benzoic acid ethyl ester 281, 9 mg, 26.8%. After cooling to room temperature washed with 1N HCl, saturated NaHCO3 and brine The organic phase was dried (MgSO4) filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (3/7)