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-(methoxymethyl)-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)-1-hydroxy-2-methoxyethyl]tetrahydro-2H-pyran-3-yl}carbamothioyl)benzamide (C41) was converted to the product using the method 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, except that the reaction was warmed to room temperature and allowed to proceed for 18 hours before work-up. The product was obtained as a solid. Yield: 17 mg, 36 μmol, 51%. LCMS m/z 473.3 [M+H+]. 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 8.24 (br d, J=7 Hz, 2H), 7.49-7.54 (m, 1H), 7.36-7.48 (m, 3H), 6.83-6.95 (m, 2H), 4.09 (br d, J=12 Hz, 1H), 3.82 (d, J=12.1 Hz, 1H), 3.62-3.69 (m, 1H), 3.37-3.45 (m, 2H), 3.34 (s, 3H), 3.09-3.16 (m, 1H), 2.94 (ddd, J=10.9, 8.2, 2.3 Hz, 1H), 1.80-1.92 (m, 1H), 1.68-1.76 (m, 1H), 0.50-0.61 (m, 2H), 0.40-0.47 (m, 1H), 0.24-0.31 (m, 1H).

Provenance & Evidence