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

HRID 522062Notes

Reaction equation

HRID 522062 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.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]1[S:33][CH:34]=[C:35]([C:37](O)=[O:38])[N:36]=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:37]([C:35]2[N:36]=[C:32]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=3)[S:33][CH:34]=2)=[O:38])[CH2:6][CH2:7]1

Participants

3

Reactant 2

HCID 156230902-(Pyridin-2-yl)-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 86713954N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(pyridin-2-yl)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-(pyridin-2-yl)thiazole-4-carboxylic acid (see Tetrahedron 2011, 67, 267) gave 326. 1H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.70-8.65 (m, 1H), 8.50 (s, 1H), 8.35-8.30 (m, 1H), 8.04-7.97 (m, 1H), 7.87 (s, 1H), 7.59-7.53 (m, 1H), 4.94-4.88 (m, 1H), 4.84-4.67 (m, 1H), 4.48-4.34 (m, 1H), 4.24-4.07 (m, 1H), 3.80 (s, 3H), 3.60-3.47 (m, 1H), 2.17-2.09 (m, 1H), 1.96-1.78 (m, 3H). LCMS (ES+) m/z 417 (M+1).

Sources & evidence

ORD record
ord-98fc52b4b43d4d52acdc597db777f837
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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