反应详情

A solution of 5-chloro-N-(5-chloropyridin-2-yl)-2-(piperidin-4-ylmethylamino)benzamide (0.44 g, 1.2 mmol) in methanol-acetic acid (95:5) (10 mL) was treated with tetrahydrothiopyran-4-one (1.34 g, 11.5 mmol) and sodium cyanoborohydride (4.6 mL of a 1 M solution in tetrahydrofuran). The reaction mixture was stirred at room temperature for 48 h, then heated at 50° C. for an additional 60 h. After cooling to room temperature, the solvent was removed in vacuo; the resulting residue was redissolved in methanol and directly applied to 5×10 g SCX columns, washed with methanol and eluted with dichloromethane-2 N ammonia in methanol (1:1). The product fractions were concentrated in vacuo and the residue was purified via silica gel chromatography. Elution with ethyl acetate followed by ethyl acetate-methanol (9:1) afforded the title compound (0.46 g, 84%) as a yellow solid, which was further purified via trituration in acetonitrile followed by separation of the yellow mother liquor.

1. temperatureheated at 50° C. for an additional 60 h
2. temperatureAfter cooling to room temperature
3. customthe solvent was removed in vacuo
4. dissolutionthe resulting residue was redissolved in methanol
5. washwashed with methanol
6. washeluted with dichloromethane-2 N ammonia in methanol (1:1)
7. concentrationThe product fractions were concentrated in vacuo
8. customthe residue was purified via silica gel chromatography
9. washElution with ethyl acetate