6-(4-(2-((Tert-butyldimethylsilyl)oxy)ethoxy)-2,6-difluorophenyl)-5-fluoropicolinic acid → N-(5-((2S,5R,6S)-5-Amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(2-hydroxyethoxy)phenyl)-5-fluoropicolinamide
Reaction equation
[F:1][C@H:2]1[C@H:8]([NH:9]C(=O)OC(C)(C)C)[CH2:7][CH2:6][C@@H:5]([C:17]2[N:21]([CH3:22])[N:20]=[CH:19][C:18]=2[N+:23]([O-])=O)[O:4][CH2:3]1.[Si]([O:33][CH2:34][CH2:35][O:36][C:37]1[CH:42]=[C:41]([F:43])[C:40]([C:44]2[N:49]=[C:48]([C:50](O)=[O:51])[CH:47]=[CH:46][C:45]=2[F:53])=[C:39]([F:54])[CH:38]=1)(C(C)(C)C)(C)C>>[NH2:9][C@H:8]1[C@H:2]([F:1])[CH2:3][O:4][C@H:5]([C:17]2[N:21]([CH3:22])[N:20]=[CH:19][C:18]=2[NH:23][C:50](=[O:51])[C:48]2[CH:47]=[CH:46][C:45]([F:53])=[C:44]([C:40]3[C:41]([F:43])=[CH:42][C:37]([O:36][CH2:35][CH2:34][OH:33])=[CH:38][C:39]=3[F:54])[N:49]=2)[CH2:6][CH2:7]1Participants
Reactant 2
Product 1
Procedure
Following the procedure for Example 111 starting from tert-butyl ((3S,4R,7S)-3-fluoro-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate (Intermediate 80), and replacing 5-((tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid with 6-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-2,6-difluorophenyl)-5-fluoropicolinic acid (see US2012/225062) gave 209. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.26 (dd, J=8.6, 4.0 Hz, 1H), 8.11 (t, J=8.9 Hz, 1H), 7.92 (s, 1H), 6.93 (d, J=10.2 Hz, 2H), 4.98 (br, 1H), 4.82 (dd, J=10.3, 3.7 Hz, 1H), 4.24 (ddt, J=49.2, 6.1, 2.6 Hz, 1H), 4.11 (t, J=4.8 Hz, 2H), 4.07-3.84 (m, 2H), 3.80-3.69 (m, 5H), 3.15-3.01 (m, 1H), 2.12-2.01 (m, 1H), 1.83-1.58 (m, 3H). LCMS (ES+) m/z 524 (M+1).
Sources & evidence
- ORD record
- ord-cfdbdbed363d45adafb5c1021783a135
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
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