反应详情

A sample of NaH (23.4 mg, 0.585 mmol) was put in a dried flask and 1.5 mL of DMSO (anhydrous) was added. Then ethyl cyanoacetate (0.062 ml, 0.585 mmol) was added slowly and stirred under N2 for 20 minutes. Then a solution of 8-iodo-6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (240 mg, 0.390 mmol, intermediate 61) in DMSO (2.0 ml) was added, followed by copper (I) iodide (111 mg, 0.585 mmol). The mixture was stirred for 2 hr at 90-95° C. Then 4 mL of water and 0.3 mL of 1N NaOH were added and the reaction mixture was stirred at 80-85° C. for 1 hr. The reaction mixture was poured into 50 mL of ethyl acetate and 10 mL of water, and the aqueous layer was extracted with ethyl acetate (20 mL×2). The combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was purified by column chromatography on silica gel, eluting with hexane/acetone (6:1-4:1) to give the title compound.

1. stirringThe mixture was stirred for 2 hr at 90-95° C
2. stirringthe reaction mixture was stirred at 80-85° C. for 1 hr
3. extractionthe aqueous layer was extracted with ethyl acetate (20 mL×2)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. concentrationconcentrated
6. customThe resulting residue was purified by column chromatography on silica gel
7. washeluting with hexane/acetone (6:1-4:1)