6-(2,6-Difluoro-4-(1-hydroxycyclobutyl)phenyl)-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-(1-hydroxycyclobutyl)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.[F:26][C:27]1[CH:32]=[C:31]([C:33]2([OH:37])[CH2:36][CH2:35][CH2:34]2)[CH:30]=[C:29]([F:38])[C:28]=1[C:39]1[N:44]=[C:43]([C:45](O)=[O:46])[CH:42]=[CH:41][C:40]=1[F:48]>>[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:45](=[O:46])[C:43]2[CH:42]=[CH:41][C:40]([F:48])=[C:39]([C:28]3[C:29]([F:38])=[CH:30][C:31]([C:33]4([OH:37])[CH2:34][CH2:35][CH2:36]4)=[CH:32][C:27]=3[F:26])[N:44]=2)[CH2:6][CH2:7]1Participants
3
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-(2,6-difluoro-4-(1-hydroxycyclobutyl)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 198. 1H NMR (400 MHz, DMSO-d6) δ 10.19 (s, 1H), 8.29 (dd, J=8.7, 4.0 Hz, 1H), 8.14 (t, J=8.8 Hz, 1H), 7.90 (s, 1H), 7.35 (d, J=9.5 Hz, 2H), 5.89 (br, 1H), 4.80 (dd, J=10.5, 3.7 Hz, 1H), 4.32-4.07 (m, 1H), 4.07-3.84 (m, 2H), 3.75 (s, 3H), 3.11-3.00 (m, 1H), 2.50-2.39 (m, 2H), 2.38-2.26 (m, 2H), 2.09-1.88 (m, 2H), 1.84-1.68 (m, 2H), 1.67-1.57 (m, 2H). LCMS (ES+) m/z 534 (M+1).
Sources & evidence
- ORD record
- ord-d9d60fc30c4a4f3d9a6e212db8e31858
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09328106B2
Reaction notes
Loading…