反应详情

A solution of intermediate 182, N-(4-fluoro-2-(3-hydroxyprop-1-ynyl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.280 g, 0.57 mmol) and triethylamine (0.12 ml, 0.86 mmol) in dichloromethane (5 ml) was cooled to 0° C., treated drop wise with methanesulfonyl chloride (0.050 ml, 0.64 mmol) and then stirred for 30 min. The reaction mixture was then diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography of the residue on silica gel (elution gradient of ethyl acetate in hexane) gave 0.245 g (75% yield) of the title material as a white solid. 1HNMR 400 MHz (CDCl3) δ ppm: 1.65 (6H, s, 2×CH3), 3.10 (3H, s, SCH3), 4.05 (4H, m, 2×CH2), 4.67 (2H, d, J=6.1 Hz, NCH2), 5.03 (2H, s, CH2), 5.29 (2H, s, OCH2), 7.07 (1H, m, aromatic), 7.18 (1H,dd, J=2.5 Hz and J=9.1 Hz, aromatic), 7.32–7.36 (3H, m, aromatics), 7.38 (1H,dd, J=5.5 Hz and J=8.6 Hz, aromatic), 7.49–7.51 (2H, m, aromatics), 7.77 (1H, broad t, NH). MS (ESI+) m/e 570 [M+H+].

1. washwashed with saturated sodium bicarbonate, brine
2. dry with materialdried over anhydrous magnesium sulfate
3. concentrationconcentrated under reduced pressure