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

HRID 1466671Notes

Reaction equation

HRID 1466671 reaction equation
[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[N:9][C:4]2=[C:3]([C:10](Cl)=[O:11])[CH:2]=1.[Si:13]([O:20][C:21]([CH3:39])([CH3:38])[CH2:22][C:23]1[S:24][C:25]([NH2:37])=[C:26]([C:28]2[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])[N:27]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].N1C=CC=CC=1>C(Cl)Cl>[Si:13]([O:20][C:21]([CH3:39])([CH3:38])[CH2:22][C:23]1[S:24][C:25]([NH:37][C:10]([C:3]2[CH:2]=[N:1][N:5]3[CH:6]=[CH:7][CH:8]=[N:9][C:4]=23)=[O:11])=[C:26]([C:28]2[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])[N:27]=1)([C:16]([CH3:18])([CH3:19])[CH3:17])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 1049PyridineHCID 19623233Pyrazolo[1,5-a]pyrimidine-3-carbonyl chlorideHCID 668473132-(2-(Tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-amine

Product 1

HCID 66846927N-(2-(2-(tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride (52.0 mg, 0.29 mmol), 2-(2-(tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-amine (103 mg, 0.24 mmol) and pyridine (2 mL) was stirred at 60° C. for 2 hours, then at room temperature for an additional 72 hours. DCM was added, the organics washed with water, sodium hydrogen carbonate (sat. aq.) and brine, then evaporated to dryness. The residues were purified by flash chromatography on silica gel (0 to 20% ethyl acetate in dichloromethane) to yield 90.6 mg (66%) of N-(2-(2-(tert-butyldimethylsilyloxy)-2-methylpropyl)-4-(5-chloro-2-methoxyphenyl)thiazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a yellow solid. LCMS (ESI) m+H=572.1; 1H NMR (400 MHz, DMSO-d6): δ 10.45 (s, br, 1H); 9.38 (dd, 1H); 8.76 (s, 1H); 8.73-8.72 (m, 1H); 7.51 (dd, 1H); 7.45 (d, 1H); 7.35 (d, 1H); 7.31 (d, 1H); 3.79 (s, 3H); 3.06 (s, 2H); 1.32 (s, 6H); 0.90 (s, 9H); 0.11 (s, 6H).

Workup

  1. washthe organics washed with water, sodium hydrogen carbonate (sat. aq.) and brine
  2. customevaporated to dryness
  3. customThe residues were purified by flash chromatography on silica gel (0 to 20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-a0ab0469d48642868ccbd6f465546447
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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