Reaction Steps
A mixture of tert-butyl ((4aR,7aR)-7a-(5-amino-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (step G of Preparation 1, 15 mg, 0.041 mmol), HATU (23.28 mg, 0.061 mmol), and DIEA (14.26 μL, 0.082 mmol) in DMF (136 μL) was stirred at rt for 2 h, and the crude product was purified by prep HPLC (NH4OAc conditions, see Preparation 3) eluting with 0-100% B over 12 min to give tert-butyl ((4aS,7aS)-7a-(2-fluoro-5-(picolinamido)phenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (12 mg, 0.025 mmol, 62.2% yield) as a white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ 10.08 (s, 1H), 8.66 (d, J=4.6 Hz, 1H), 8.31 (d, J=7.8 Hz, 1H), 8.06 (dt, J=8.4, 3.6 Hz, 1H), 7.94 (td, J=7.7, 1.7 Hz, 1H), 7.70 (d, J=4.3 Hz, 1H), 7.53 (ddd, J=7.5, 4.8, 1.0 Hz, 1H), 7.13 (dd, J=10.8, 9.0 Hz, 1H), 4.23-4.11 (m, 2H), 3.30 (d, J=12.4 Hz, 1H), 3.00 (br. s., 1H), 2.92-2.86 (m, 1H), 2.39 (dd, J=12.6, 7.4 Hz, 1H), 2.26-2.15 (m, 1H), 2.10 (s, 4H), 2.03 (s, 1H), 1.51 (s, 9H).
