N-[(6R)-6-[(benzyloxy)methyl]-8a-(5-cyano-2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide → N-[(4aR,6R,8aS)-8a-(5-cyano-2,4-difluorophenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide
Reaction equation
Br[C:2]1[C:3]([F:30])=[CH:4][C:5]([F:29])=[C:6]([C@:8]23[CH2:17][O:16][C@@H:15]([CH2:18][F:19])[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:20][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:9]3)[CH:7]=1.C(OC[C@@H]1OC[C:43]2(C3C=C(C#N)C(F)=CC=3F)[N:44]=C(NC(=O)C3C=CC=CC=3)SCC2C1)C1C=CC=CC=1>>[C:43]([C:2]1[C:3]([F:30])=[CH:4][C:5]([F:29])=[C:6]([C@:8]23[CH2:17][O:16][C@@H:15]([CH2:18][F:19])[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:20][C:21](=[O:28])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[N:9]3)[CH:7]=1)#[N:44]Participants
Reactant 2
Product 1
Procedure
N-[(4aR,6R,8aS)-8a-(5-Bromo-2,4-difluorophenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C13) was converted to the product using the method described for the synthesis of N-[(6R)-6-[(benzyloxy)methyl]-8a-(5-cyano-2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C10) in Example 1. Yield: 98.5 mg, 0.220 mmol, 44%. LCMS m/z 446.2 [M+H+]. 1H NMR (400 MHz, CD3OD), δ 8.06 (d, J=7.2 Hz, 2H), 7.85 (t, J=7.8 Hz, 1H), 7.54-7.57 (m, 1H), 7.45-7.49 (m, 2H), 7.37 (dd, J=12.1, 9.2 Hz, 1H), 4.44-4.51 (m, 1H), 4.32-4.39 (m, 1H), 4.06-4.10 (m, 1H), 3.89-4.0 (m, 2H), 3.11-3.19 (m, 1H), 2.96 (dd, J=13.3, 4.1 Hz, 1H), 2.75 (dd, J=13.3, 2.9 Hz, 1H), 1.83-1.93 (m, 1H), 1.64-1.69 (m, 1H).
Sources & evidence
- ORD record
- ord-21a83a811a304d578c6252e4beea1189
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822456B2
Reaction notes
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