反应详情

To a stirred solution of 2-chloro-2′-fluoro-5-methoxy[1,1′-biphenyl]-4-carboxylic acid of Step A (3.80 g, 13.5 mmol) in tetrahydrofuran (20 mL) containing a catalytic amount of N,N-dimethylformamide was added dropwise thionyl chloride (1.77 g, 14.9 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (2.49 g, 13.5 mmol) in tetrahydrofuran (20 mL) containing triethylamine (3.0 g, 29.8 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Recrystallization of the residue from ethyl acetate/heptane provided the title compound as a pale yellow solid, m.p. 192–194° C., found to be 99.99% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase: gradientfrom 10 to 100% of acetonitrile/water containing 0.1% phosphoric acid, 7 minute gradient].

1. stirringThe reaction mixture was stirred for 2 hours
2. washwashed with saturated aqueous sodium bicarbonate and brine
3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
4. filtrationfiltered
5. customevaporated to dryness
6. customRecrystallization of the residue from ethyl acetate/heptane