反应详情

To a stirred solution of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyri din-1-yl)piperidine-1-carboxamide, potassium salt, [Burgey et al. U.S. Pat. No. 6,953,790 B2] (1.00 g, 1.65 mmol) in anhydrous, degassed DMF (200 mL) at ambient temperature was added dibenzyl chloromethyl phosphate [Mäntylä et al. Tetrahedron Lett. 2002, 43, 3793] (0.54 g, 1.65 mmol). The resulting mixture was stirred at ambient temperature for 4 h, filtered, and purified by preparative HPLC on a C18 reversed phase column, eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 0:100:0.1. The product-containing fractions were poured into saturated aqueous NaHCO3 and extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=857.7 (M+1).

1. custom6,953,790 B2] (1.00 g, 1.65 mmol) in anhydrous, degassed DMF (200 mL) at ambient temperature
2. filtrationfiltered
3. custompurified by preparative HPLC on a C18
4. washeluting with a gradient of H2O
5. additionThe product-containing fractions were poured into saturated aqueous NaHCO3
6. extractionextracted with EtOAc (2×50 mL)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo