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

HRID 521972Notes

Reaction equation

HRID 521972 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][O: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])[CH2:36][O:35][CH2:34]4)=[CH:32][C:27]=3[F:26])[N:44]=2)[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 706546576-(2,6-Difluoro-4-(3-hydroxyoxetan-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 73437697N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2,6-difluoro-4-(3-hydroxyoxetan-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-hydroxyoxetan-3-yl)phenyl)-5-fluoropicolinic acid (see US2012/225062) gave 193. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.30 (dd, J=8.7, 4.0 Hz, 1H), 8.23-8.12 (m, 1H), 7.90 (s, 1H), 7.49 (d, J=9.7 Hz, 2H), 4.81 (t, J=5.7 Hz, 3H), 4.73 (dd, J=7.0, 1.4 Hz, 2H), 4.41-4.17 (m, 1H), 4.10-3.87 (m, 2H), 3.76 (s, 3H), 3.19-3.09 (m, 1H), 2.11-2.02 (m, 1H), 1.69 (s, 3H). LCMS (ES+) m/z 536 (M+1).

Sources & evidence

ORD record
ord-30caa9585f674ce883b4b2176774096b
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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