反应详情

To a stirred solution of tert-butyl ((4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate (4.70 g) and 5-methoxypyrazine-2-carboxylic acid (2.65 g), in DCM (60 mL) was added N,N-diisopropylethylamine (8.0 mL) and (1H-benzotriazol-1-yloxy)tripyrrolidin-1-yl)phosphonium hexafluorophosphate (9.0 g, portionwise over 10 min). The reaction mixture was stirred at RT for 18 h, concentrated under vacuum to circa 20 mL, and sodium bicarbonate (sat., aq., 100 mL) was added. The mixture was extracted with EtOAc (2×150 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (0% to 50% EtOAc in DCM gradient) to afford the title compound (6.71 g, approx. purity 90%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.54 (m, 9H), 2.71-2.83 (br. s., 1H), 3.03-3.34 (br. s., 1H), 3.81-4.01 (br. s., 1H), 4.09 (m, 3H), 4.48-4.75 (m, 4H), 7.05-7.20 (m, 1H), 7.36-7.58 (m, 1H), 7.93-8.02 (m, 1H), 8.20 (d, J=1.3 Hz, 1H), 9.04 (d, J=1.3 Hz, 1H), 9.53 (br. s., 1H)

1. concentrationconcentrated under vacuum to circa 20 mL, and sodium bicarbonate (sat., aq., 100 mL)
2. additionwas added
3. extractionThe mixture was extracted with EtOAc (2×150 mL)
4. dry with materialthe combined organic portions were dried over MgSO4
5. customevaporated
6. custompurified by silica gel chromatography (0% to 50% EtOAc in DCM gradient)