反应详情

To a solution of 8-iodo-6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (787 mg, 1.28 mmol, intermediate 61) in 2 ml of THF was added a solution of isopropyl magnesium chloride (5.12 ml, 10.24 mmol) in THF (2M) at 0° C. and stirred for 30 min. Then the reaction mixture was added to a solution of diethyl oxalate (4.34 ml, 32 mmol) in 8 mL of toluene and stirred for 30 min. at 0° C. Then the reaction mixture was poured into 3.5 mL of 2 N HCl and 5 mL of ice-water, and the pH was adjusted to pH=7-8 with aqueous NaHCO3. The mixture was extracted with ethyl acetate (3×20 ml) and dried with Na2SO4. The combined organic layers were evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel, eluting with hexane/ethyl acetate (4/1-3/1) to give title compound 509; Mass Spectrum: m/e=634 (M+1). Further elution of the column afforded the title compound 510; Mass Spectrum: m/e=590 (M+1).

1. stirringstirred for 30 min. at 0° C
2. extractionThe mixture was extracted with ethyl acetate (3×20 ml)
3. dry with materialdried with Na2SO4
4. customThe combined organic layers were evaporated under reduced pressure
5. customThe resulting residue was purified by column chromatography on silica gel
6. washeluting with hexane/ethyl acetate (4/1-3/1)