反应详情

10-[4-(3-hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-benzoyl]-10,11-dihydro-5H pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (0.200 g, 0.438 mmol) of Step A, N-methylpiperazine (0.058 mL, 0.526 mmol), 1-hydroxy benzotriazole (0.065 g, 0.482 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.092 g, 0.482 mmol) were combined in amine-free N,N-dimethylformamide (1.8 mL), followed by addition of N,N-diisopropylethyl amine (0.114 mL, 0.657 mmol). The reaction was stirred at room temperature for 18 hours, then diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate, and brine. The combined aqueous washings were saturated with sodium chloride and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel using a solvent gradient from 0 to 8% of methanol in chloroform to afford 0.180 g of the title compound as a white solid.

1. washwashed with water, saturated aqueous sodium bicarbonate, and brine
2. extractionextracted with ethyl acetate
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by flash column chromatography on silica gel using a solvent gradient from 0 to 8% of methanol in chloroform