HCID 90253541, compound → HCID 90253554, compound

Participants

Reaction Steps

N-{(4aR,6R,8aS)-8a-(2,4-Difluorophenyl)-6-[(2S)-tetrahydrofuran-2-yl]-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl}benzamide (C103) was converted to the product using the method described for the synthesis of (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-amine, hydrochloride salt (6) in Example 6. Purification by reversed phase HPLC {Column: Phenomenex Gemini C18, 8 μm; Gradient: 36% to 56% acetonitrile in water [ammonia (pH 10)]} provided the product as a white solid. Yield: 193 mg, 0.545 mmol, 25%. LCMS m/z 355.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.31-7.37 (m, 1H), 6.75-6.87 (m, 2H), 4.06 (dd, J=11, 2.0 Hz, 1H), 3.73-3.90 (m, 4H), 3.51 (ddd, J=10.8, 6.5, 2.3 Hz, 1H), 2.95 (dd, J=12.0, 4.0 Hz, 1H), 2.83-2.89 (m, 1H), 2.60 (dd, J=12.3, 2.3 Hz, 1H), 1.97-2.05 (m, 1H), 1.73-1.94 (m, 4H), 1.64-1.69 (m, 1H).

Provenance & Evidence