5-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid → (R)-5-Amino-2-(2,6-difluorophenyl)-N-(5-(2-ethylpiperazin-1-yl)-1-methyl-1H-pyrazol-4-yl)thiazole-4-carboxamide

HRID 1915850Notes

Reaction equation

HRID 1915850 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][N:5]([CH3:22])[C:6]=1[N:7]1[CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][C@H:8]1[CH2:20][CH3:21].C(OC([NH:30][C:31]1[S:35][C:34]([C:36]2[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:37]=2[F:43])=[N:33][C:32]=1[C:44](O)=[O:45])=O)(C)(C)C>>[NH2:30][C:31]1[S:35][C:34]([C:36]2[C:41]([F:42])=[CH:40][CH:39]=[CH:38][C:37]=2[F:43])=[N:33][C:32]=1[C:44]([NH:1][C:2]1[CH:3]=[N:4][N:5]([CH3:22])[C:6]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][C@H:8]1[CH2:20][CH3:21])=[O:45]

Participants

3

Reactant 2

HCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86679973(R)-tert-butyl 4-(4-amino-1-methyl-1H-pyrazol-5-yl)-3-ethylpiperazine-1-carboxylate

Product 1

HCID 71539966(R)-5-Amino-2-(2,6-difluorophenyl)-N-(5-(2-ethylpiperazin-1-yl)-1-methyl-1H-pyrazol-4-yl)thiazole-4-carboxamideYield 21%

Procedure

Following the procedure for Example 112, reacting (R)-tert-butyl 4-(4-amino-1-methyl-1H-pyrazol-5-yl)-3-ethylpiperazine-1-carboxylate and 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid from Example 25 gave 114 as a white solid (30 mg, 21% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 7.91 (s, 1H), 7.36-7.27 (m, 1H), 7.02 (t, J=8.9 Hz, 2H), 6.24 (s, 2H), 3.76 (s, 3H), 3.25-3.15 (m, 2H), 3.11-2.90 (m, 4H), 2.58 (t, J=5.5 Hz, 1H), 1.41-1.31 (m, 1H), 1.28-1.14 (m, 1H), 0.79 (t, J=7.5 Hz, 3H). Alkyl NH not observed. LCMS (ES+) m/z 448 (M+1).

Sources & evidence

ORD record
ord-2e9247d8d7cb4ac9b59cc6aa2c42840d
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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