6-(2,6-Difluoro-4-(methoxymethyl)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-(methoxymethyl)phenyl)-5-fluoropicolinamide

HRID 521978Notes

Reaction equation

HRID 521978 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]([CH2:33][O:34][CH3:35])[CH:30]=[C:29]([F:36])[C:28]=1[C:37]1[N:42]=[C:41]([C:43](O)=[O:44])[CH:40]=[CH:39][C:38]=1[F:46]>>[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:43](=[O:44])[C:41]2[CH:40]=[CH:39][C:38]([F:46])=[C:37]([C:28]3[C:29]([F:36])=[CH:30][C:31]([CH2:33][O:34][CH3:35])=[CH:32][C:27]=3[F:26])[N:42]=2)[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 706549716-(2,6-Difluoro-4-(methoxymethyl)phenyl)-5-fluoropicolinic acidHCID 86713841tert-butyl ((3S,4R,7S)-3-fluoro-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate2×

Product 1

HCID 73438190N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(methoxymethyl)phenyl)-5-fluoropicolinamide

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-(methoxymethyl)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 199. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.29 (dd, J=8.6, 4.0 Hz, 1H), 8.15 (t, J=8.8 Hz, 1H), 7.91 (s, 1H), 7.24 (d, J=9.0 Hz, 2H), 4.81 (dd, J=10.3, 3.7 Hz, 1H), 4.53 (s, 2H), 4.31-4.07 (m, 1H), 4.02-3.83 (m, 2H), 3.75 (s, 3H), 3.36 (s, 3H), 3.11-2.98 (m, 1H), 2.10-2.00 (m, 1H), 1.82-1.57 (m, 3H). LCMS (ES+) m/z 508 (M+1).

Sources & evidence

ORD record
ord-bf474f5edad84cf8b96e928580b32368
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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