6-(2,6-Difluoro-4-(3-methoxyoxetan-3-yl)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-(3-methoxyoxetan-3-yl)phenyl)-5-fluoropicolinamide

HRID 521981Notes

Reaction equation

HRID 521981 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([O:37][CH3:38])[CH2:36][O:35][CH2:34]2)[CH:30]=[C:29]([F:39])[C:28]=1[C:40]1[N:45]=[C:44]([C:46](O)=[O:47])[CH:43]=[CH:42][C:41]=1[F:49]>>[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:46](=[O:47])[C:44]2[CH:43]=[CH:42][C:41]([F:49])=[C:40]([C:28]3[C:29]([F:39])=[CH:30][C:31]([C:33]4([O:37][CH3:38])[CH2:36][O:35][CH2:34]4)=[CH:32][C:27]=3[F:26])[N:45]=2)[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 706550966-(2,6-Difluoro-4-(3-methoxyoxetan-3-yl)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 86713890N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(3-methoxyoxetan-3-yl)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-(3-methoxyoxetan-3-yl)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 202. 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.32 (dd, J=8.7, 4.0 Hz, 1H), 8.17 (t, J=8.9 Hz, 1H), 7.94 (s, 1H), 7.42 (d, J=9.3 Hz, 2H), 4.87-4.75 (m, 5H), 4.17 (ddt, J=49.0, 6.1, 2.6 Hz, 1H), 4.03-3.84 (m, 2H), 3.75 (s, 3H), 3.14 (s, 3H), 3.12-2.98 (m, 1H), 2.11-2.00 (m, 1H), 1.80-1.57 (m, 3H). LCMS (ES+) m/z 550 (M+1).

Sources & evidence

ORD record
ord-64430948e96f45f5a0442a00fa80b6cb
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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