Triethylamine → 5-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine

HRID 558564Notes

Reaction equation

HRID 558564 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20](I)=[C:10]3[N:9]=2)=[CH:4][C:3]=1[CH3:22].[CH3:23][Si:24]([C:27]#[CH:28])([CH3:26])[CH3:25].C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20]([C:28]#[C:27][Si:24]([CH3:26])([CH3:25])[CH3:23])=[C:10]3[N:9]=2)=[CH:4][C:3]=1[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 670008925-(4-Chloro-3-methyl-phenyl)-3-iodo-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 670004775-(4-Chloro-3-methyl-phenyl)-7-trifluoromethyl-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidineYield 114.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(4-chloro-3-methyl-phenyl)-3-iodo-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine (5.85 g, 12.4 mmol), trimethylsilylacetylene (3.33 mL, 24.1 mmol) and triethylamine (3.71 mL, 26.7 mmol) in N,N-dimethylformamide (20 mL) was stirred for 10 min at room temperature while being purged with Argon, then PdCl2(PPh3)2 (94 mg, 1 mol %), PPh3 (35 mg, 1 mol %) and CuI (8 mg, 0.3 mol %) were added. Stirring was continued at 90° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (150 mL), washed with water (2×50 mL) and brine (70 mL), dried (MgSO4) and evaporated to give 5-(4-chloro-3-methyl-phenyl)-7-trifluoromethyl-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (5.79 g, 106%) as an orange solid, which was dissolved in THF (70 mL) and MeOH (70 mL), while stirring at 0° C. potassium carbonate (196 mg, 1.42 mmol) was added and the mixture was stirred at 0° C. for 5 h. The mixture was diluted with ice water (250 mL) and extracted with TBME (3×250 mL). The combined organic layers were washed with brine (300 mL), dried (MgSO4) and evaporated. The crude product was further purified by column chromatography on silica gel (heptane/EtOAc 9:1) followed by trituration with heptane to give 5-(4-chloro-3-methyl-phenyl)-3-ethynyl-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine (3.22 g, 68%) as an orange solid. MS (EI) 335.0 [(M+H)+]; mp 166° C.

Workup

  1. customwhile being purged with Argon
  2. additionPdCl2(PPh3)2 (94 mg, 1 mol %), PPh3 (35 mg, 1 mol %) and CuI (8 mg, 0.3 mol %) were added
  3. stirringStirring
  4. waitwas continued at 90° C. for 4 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. additiondiluted with ethyl acetate (150 mL)
  7. washwashed with water (2×50 mL) and brine (70 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-2205e99bc96546a2b48e16bd871d6afc
Source dataset
uspto-grants-2011_11
Patent number
US08063048B2

Reaction notes

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