反应详情

DIAD (38.2 μl, 0.196 mmol) was added to a stirred mixture of 1-(azetidin-1-yl)-2-(2-fluoro-4-hydroxyphenyl)ethanone (41.1 mg, 0.196 mmol), 2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethanol (57 mg, 0.196 mmol), and triphenyl phosphine (51.5 mg, 0.196 mmol) in toluene (327 μl). The mixture was degassed (3×) and stirred at RT for 2 hours. The mixture was diluted with ethyl acetate (20 mL), washed with water (20 ml), the layers separated, the aqueous phase extracted with EtOAc (20 ml), the organic fractions combined, washed with brine (35 ml), dried over sodium sulfate, filtered and the volatiles removed in vac. The residue was purified by column chromatography on silica gel, Biotage 25 g, using a gradient eluant of 0-100% EtOAc/hexanes to afford the title compound. LC/MS (m/z): 482 (M+H)+. GPR119 Human EC50: 0.94 nM

1. customThe mixture was degassed (3×)
2. additionThe mixture was diluted with ethyl acetate (20 mL)
3. washwashed with water (20 ml)
4. customthe layers separated
5. extractionthe aqueous phase extracted with EtOAc (20 ml)
6. washwashed with brine (35 ml)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. customthe volatiles removed in vac
10. customThe residue was purified by column chromatography on silica gel, Biotage 25 g