5-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid → (R)-tert-butyl 2-(2,6-difluorophenyl)-4-(1-cyclopropylmethyl-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

HRID 2089318Notes

Reaction equation

HRID 2089318 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]([N:10]3[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:12][CH2:11]3)=[C:8]([N+:24]([O-])=O)[CH:7]=[N:6]2)[CH2:3][CH2:2]1.[C:27]([O:31][C:32]([NH:34][C:35]1[S:39][C:38]([C:40]2[C:45]([F:46])=[CH:44][CH:43]=[CH:42][C:41]=2[F:47])=[N:37][C:36]=1[C:48](O)=[O:49])=[O:33])([CH3:30])([CH3:29])[CH3:28]>>[F:47][C:41]1[CH:42]=[CH:43][CH:44]=[C:45]([F:46])[C:40]=1[C:38]1[S:39][C:35]([NH:34][C:32](=[O:33])[O:31][C:27]([CH3:29])([CH3:28])[CH3:30])=[C:36]([C:48](=[O:49])[NH:24][C:8]2[CH:7]=[N:6][N:5]([CH2:4][CH:1]3[CH2:3][CH2:2]3)[C:9]=2[N:10]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:12][CH2:11]2)[N:37]=1

Participants

3

Reactant 2

HCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86658414(R)-N-(1-(1-cyclopropylmethyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl)-2,2,2-trifluoroacetamide

Product 1

HCID 86658418(R)-tert-butyl 2-(2,6-difluorophenyl)-4-(1-cyclopropylmethyl-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamateYield 77%

Procedure

Following the procedure for Example 517 starting with (R)-N-(1-(1-cyclopropylmethyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl)-2,2,2-trifluoroacetamide and 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid gave (R)-tert-butyl 2-(2,6-difluorophenyl)-4-(1-cyclopropylmethyl-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate as a cream solid (136 mg, 77%). 1H-NMR (400 MHz, CDCl3) δ 10.39 (s, 1H), 8.75 (s, 1H), 7.95 (s, 1H), 7.41-7.36 (m, 1H), 7.10-7.02 (m, 2H), 6.37 (d, J=8 Hz, 1H), 4.25-4.10 (m, 1H), 3.90-3.83 (m, 2H), 3.43-3.31 (m, 2H), 3.30-3.15 (m, 2H), 2.25-2.05 (m, 2H), 2.03-1.70 (m, 4H), 1.57 (s, 9H) 1.35-1.20 (m, 1H), 0.64-0.59 (m, 2H), 0.43-0.38 (m, 2H).

Sources & evidence

ORD record
ord-00fbe14de61141cdb2775479897ad35f
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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