N-[(4aR,6R,8aS)-6-[(benzyloxy)methyl]-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide → rel-N-[(4S,4aR,6R,8aS)-6-cyclopropyl-8a-(2,4-difluorophenyl)-4-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Participants

Reaction Steps

rel-N-({(3S,4R,6R)-6-Cyclopropyl-3-(2,4-difluorophenyl)-4-[(1R)-2-fluoro-1-hydroxyethyl]tetrahydro-2H-pyran-3-yl}carbamothioyl)benzamide (C46) was converted to the product using the chemistry described for synthesis of N-[(4aR,6R,8aS)-6-[(benzyloxy)methyl]-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C8) in Preparation P1. The product was obtained as an oil. Yield: 36 mg, 78 μmol, 65%. LCMS m/z 461.2 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.21 (br d, J=7.2 Hz, 2H), 7.50-7.56 (m, 1H), 7.43-7.49 (m, 2H), 7.39 (ddd, J=9.0, 9.0, 6.3 Hz, 1H), 6.86-6.96 (m, 2H), 4.61 (ddd, half of ABX pattern, J=46.9, 9.5, 7.8 Hz, 1H), 4.44 (ddd, half of ABX pattern, J=46.2, 9.5, 6.6 Hz, 1H), 4.10 (dd, J=12.1, 1.8 Hz, 1H), 3.82 (d, J=12.3 Hz, 1H), 3.47-3.56 (m, 1H), 3.16-3.23 (m, 1H), 2.94 (ddd, J=11.0, 8.0, 2.5 Hz, 1H), 1.81-1.93 (m, 1H), 1.75-1.81 (m, 1H), 0.95-1.04 (m, 1H), 0.51-0.62 (m, 2H), 0.40-0.47 (m, 1H), 0.24-0.31 (m, 1H).

Provenance & Evidence