Diisopropylethylamine → tert-butyl ((4aS,5S,7aS)-7a-(2,3-difluoro-5-(5-methoxypyrazine-2-carboxamido)phenyl)-5-(difluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate

Participants

Reaction Steps

tert-butyl ((4aS,5S,7aS)-7a-(5-amino-2,3-difluorophenyl)-5-(difluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate, synthesized in preparation example 1-(13), (100 mg) was dissolved in DCM (2 mL) and 5-methoxypyrazine-2-carboxylic acid (50 mg), N,N-diisopropylethylamine (100 mg) and (1H-benzotriazol-1-yloxy)tripyrrolidin-1-yl)phosphonium hexafluorophosphate (175 mg) were added. The reaction mixture was stirred at RT for 3 days, and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (2×40 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (EtOAc/hexanes gradient) to afford the title compound (108 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.54 (s, 9H), 2.82 (dd, J=13.5, 3.4 Hz, 1H), 3.08 (d, J=12.9 Hz, 1H), 3.33-3.45 (m, 1H), 3.84-3.93 (m, 1H), 4.10 (s, 3H), 4.46-4.65 (m, 2H), 5.97 (dt, J=3.8, 56.6 Hz, 1H), 7.08 (br. s., 1H), 7.27-7.36 (m, 1H), 8.14 (ddd, J=11.6, 7.0, 2.7 Hz, 1H), 8.20 (d, J=1.3 Hz, 1H), 9.04 (d, J=1.3 Hz, 1H), 9.55 (s, 1H)

Provenance & Evidence