2-(2,6-Difluorophenyl)-1,3-thiazole-4-carboxylic acid → N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide

HRID 522057Notes

Reaction equation

HRID 522057 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]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[C:34]1[S:35][CH:36]=[C:37]([C:39](O)=[O:40])[N:38]=1>>[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:39]([C:37]2[N:38]=[C:34]([C:28]3[C:27]([F:26])=[CH:32][CH:31]=[CH:30][C:29]=3[F:33])[S:35][CH:36]=2)=[O:40])[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 242784542-(2,6-Difluorophenyl)-1,3-thiazole-4-carboxylic acidHCID 86713841tert-butyl ((3S,4R,7S)-3-fluoro-7-(1-methyl-4-nitro-1H-pyrazol-5-yl)oxepan-4-yl)carbamate2×

Product 1

HCID 86713949N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide

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 2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (see US2012/225061) gave 321. 1H NMR (400 MHz, DMSO-d6) δ 9.94-9.85 (m, 1H), 8.63 (d, J=1.2 Hz, 1H), 7.81 (d, J=1.1 Hz, 1H), 7.69-7.60 (m, 1H), 7.33 (t, J=8.7 Hz, 2H), 4.81 (dd, J=10.9, 3.5 Hz, 1H), 4.44-4.24 (m, 1H), 4.23-4.10 (m, 1H), 3.99 (ddd, J=37.2, 14.8, 3.5 Hz, 1H), 3.77 (s, 3H), 2.11-2.02 (m, 1H), 1.90-1.76 (m, 1H), 1.75-1.63 (m, 2H). LCMS (ES+) m/z 452 (M+1).

Sources & evidence

ORD record
ord-2e722181b29649e8b7cd2b6a552f236e
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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