N-(2-(2-(tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide → N-(4-(5-chloro-2-methoxyphenyl)-2-(2-hydroxy-2-methylpropyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1466672Notes

Reaction equation

HRID 1466672 reaction equation
[Si]([O:8][C:9]([CH3:38])([CH3:37])[CH2:10][C:11]1[S:12][C:13]([NH:25][C:26]([C:28]2[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][CH:34]=[N:33][C:32]=23)=[O:27])=[C:14]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])[N:15]=1)(C(C)(C)C)(C)C>FC(F)(F)C(O)=O>[Cl:22][C:20]1[CH:19]=[CH:18][C:17]([O:23][CH3:24])=[C:16]([C:14]2[N:15]=[C:11]([CH2:10][C:9]([OH:8])([CH3:38])[CH3:37])[S:12][C:13]=2[NH:25][C:26]([C:28]2[CH:29]=[N:30][N:31]3[CH:36]=[CH:35][CH:34]=[N:33][C:32]=23)=[O:27])[CH:21]=1

Participants

3

Reactant 1

HCID 66846927N-(2-(2-(tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 49857814N-(4-(5-chloro-2-methoxyphenyl)-2-(2-hydroxy-2-methylpropyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of N-(2-(2-(tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (20 mg, 35.0 μmol) in trifluoroacetic acid (3 mL) was stirred for 7 days at room temperature. The reaction was evaporated under vacuum and the crude product purified by reverse phase HPLC then lyophilized to afford 11.3 mg (71%) of N-(4-(5-chloro-2-methoxyphenyl)-2-(2-hydroxy-2-methylpropyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (ESI) m+H=458.0; 1H NMR (400 MHz, DMSO-d6): δ 10.43 (s, br, 1H); 9.38 (dd, 1H); 8.74 (dd, 1H); 8.73 (s, 1H); 7.51 (dd, 1H); 7.46 (d, 1H); 7.35 (s, 1H); 7.32-7.31 (m, 1H); 4.76 (s, 1H); 3.79 (s, 3H); 3.01 (s, 2H); 1.19 (s, 6H).

Workup

  1. customThe reaction was evaporated under vacuum
  2. customthe crude product purified by reverse phase HPLC

Sources & evidence

ORD record
ord-55ef5dca8d314621a730476ba68cc723
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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