反应详情

A solution of N-[(4aR,7aS)-6-(5-fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (215 mg, 0.496 mmol), O-methylhydroxylamine hydrochloride (207 mg, 2.48 mmol), and pyridine (392 mg, 4.96 mmol) in ethanol (5 ml) is stirred at 55° C. for 4 hours. The mixture is quenched with a solution of saturated sodium bicarbonate in water, and extracted with ethyl acetate. The organic layers are combined, dried, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by silica gel flash chromatography, eluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1) to give a residue as the free base of the title compound. The residue is dissolved in 1 N hydrochloric acid (4 ml), and the solvent removed by a stream of nitrogen. The resulting solid is further purified by dissolving in 1/1 acetonitrile/methanol (4 ml) and precipitating with ethyl ether (2-3 ml). The solid is collected and dried under reduced pressure at 50° C. to give the title compound (0.10 g, 55%). ES/MS (m/e): 330 (M+H).

1. customThe mixture is quenched with a solution of saturated sodium bicarbonate in water
2. extractionextracted with ethyl acetate
3. customdried
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customto give a residue
7. customThe residue is purified by silica gel flash chromatography
8. washeluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1)