反应详情

A solution of the 7,8-dimethoxy-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]methanone of Example 12, Step D (0.31 mmol), diphosgene (1.1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (5 mL) was stirred at room temperature overnight. The solvent was removed in vacuo, the residue was dissolved in dichloromethane (5 mL), and then triethylamine (1.5 equiv.) and 4-piperidone (1.5 equiv.) were added. The reaction mixture was stirred overnight, washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane and then chromatographed again with 2% methanol in ethyl acetate to provide the title compound as a yellow solid, m.p. 132–134° C.

1. customThe solvent was removed in vacuo
2. dissolutionthe residue was dissolved in dichloromethane (5 mL)
3. washwashed with water
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. customevaporated to dryness
7. customThe residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane
8. customchromatographed again with 2% methanol in ethyl acetate