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

HRID 522060Notes

Reaction equation

HRID 522060 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.C(OC([NH:33][C:34]1[S:38][C:37]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=2[F:46])=[N:36][C:35]=1[C:47](O)=[O:48])=O)(C)(C)C>>[NH2:33][C:34]1[S:38][C:37]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=2[F:46])=[N:36][C:35]=1[C:47]([NH:23][C:18]1[CH:19]=[N:20][N:21]([CH3:22])[C:17]=1[C@@H:5]1[CH2:6][CH2:7][C@@H:8]([NH2:9])[C@H:2]([F:1])[CH2:3][O:4]1)=[O:48]

Participants

3

Reactant 2

HCID 581821445-(Tert-butoxycarbonylamino)-2-(2,3-difluorophenyl)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 867139525-amino-N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3-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 5-((tert-butoxycarbonyl)amino)-2-(2,3-difluorophenyl)thiazole-4-carboxylic acid (Example 25) gave 324. 1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.07 (dd, J=8.3, 6.5 Hz, 1H), 7.87 (s, 1H), 7.52 (s, 2H), 7.48-7.38 (m, 1H), 7.31-7.22 (m, 1H), 4.87-4.80 (m, 1H), 4.56-4.38 (m, 1H), 4.36-4.23 (m, 1H), 4.16-3.99 (m, 1H), 3.76 (s, 3H), 2.09-2.01 (m, 1H), 1.87-1.66 (m, 5H). LCMS (ES+) m/z 467 (M+1).

Sources & evidence

ORD record
ord-3e50236c522947b0aa108d2f06f6ae46
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

Loading…