Triethylamine → 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amide

HRID 529759Notes

Reaction equation

HRID 529759 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11](Cl)=[O:12])=[C:4]2[N:3]=1.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([O:35][CH:36]([F:38])[F:37])=[C:19]([C:21]2[N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:24]=[CH:23][C:22]=2[NH2:34])[CH:20]=1.C(N(CC)CC)C>ClCCl>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([O:35][CH:36]([F:37])[F:38])=[C:19]([C:21]2[N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:31])[CH3:32])[N:24]=[CH:23][C:22]=2[NH:34][C:11]([C:10]2[CH:9]=[N:8][N:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[N:3][C:4]=23)=[O:12])[CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 580631365-Chloropyrazolo[1,5-a]pyrimidine-3-carbonyl chlorideHCID 1231430925-(5-chloro-2-difluoromethoxyphenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-ylamine

Product 1

HCID 1317356225-chloro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amideYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carbonyl chloride (500 mg, 2.3 mmol) (prepared according to the procedure in Journal of Medicinal Chemistry, 55(22), 10090-10107; 2012) and 5-(5-chloro-2-difluoromethoxyphenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-ylamine (868 mg, 2.3 mmol) were suspended in triethylamine (0.35 mL, 2.5 mmol) and DCM (10 mL) and the mixture was left to stir at room temperature for 2 hours. The reaction mixture was diluted with dichloromethane and the resultant organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, and brine, dried (Na2SO4) and evaporated to afford an oil. The resultant oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM. Collecting appropriate fractions, followed by evaporation gave 5-chloro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amide as a brown oil (1.19 g, 91%). 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.07 (s, 1H), 8.72 (s, 1H), 8.67 (d, 1H, J=7.3 Hz), 8.38 (s, 1H), 7.60 (d, 1H, J=2.3 Hz), 7.51 (dd, 1H, J=2.6, 8.8 Hz), 7.38 (d, 1H, J=8.9 Hz), 6.95 (d, 1H, J=7.2 Hz), 6.43 (t, 1H, J=72.8 Hz), 5.41 (d, 1H, J=10.9 Hz), 5.31 (d, 1H, J=11.0 Hz), 3.76-3.49 (m, 2H), 1.27 (s, 1H), 0.94-0.84 (m, 2H), 0.00 (s, 9H).

Workup

  1. customprepared
  2. washthe resultant organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, and brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customto afford an oil
  6. customThe resultant oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM
  7. customCollecting appropriate fractions
  8. customfollowed by evaporation

Sources & evidence

ORD record
ord-ae0d7fe425da44a693c38350bc371e87
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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