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

HRID 1293671Notes

Reaction equation

HRID 1293671 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][C:8]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)=[N:7][C:6]=12.[CH3:25][Si:26]([C:29]#[CH:30])([CH3:28])[CH3:27].C(N(CC)CC)C>CN(C)C=O>[F:12][C:11]([F:14])([F:13])[C:10]1[N:5]2[N:4]=[CH:3][C:2]([C:30]#[C:29][Si:26]([CH3:28])([CH3:27])[CH3:25])=[C:6]2[N:7]=[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 866079983-Iodo-7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 866079997-Trifluoromethyl-5-(3-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidineYield 102.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-iodo-7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (6.49 g, 14.2 mmol), trimethylsilylacetylene (3.54 mL, 25.6 mmol) and triethylamine (3.94 mL, 28.4 mmol) in N,N-dimethylformamide (15 mL) was stirred for 10 min at room temperature while being purged with Argon, then PdCl2(PPh3)2 (100 mg, 1 mol %), PPh3 (37 mg, 1 mol %) and CuI (8 mg, 0.3 mol %) were added. Stirring was continued at 90° C. for 4.5 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 7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (6.2 g, 102%) as a light brown solid, which was dissolved in THF (30 mL) and MeOH (70 mL), while stirring at 0° C. potassium carbonate (200 mg, 1.45 mmol) was added and the mixture was stirred at 0° C. for 5 h. The mixture was diluted with ice water (200 mL) and extracted with TBME (3×200 mL). The combined organic layers were washed with brine (300 mL), dried (MgSO4) and evaporated. The crude product was further purified by silica gel column chromatography (heptane/EtOAc 9:1) followed by trituration with heptane to give 3-ethynyl-7-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (3.23 g, 63%) as an orange solid. MS (EI) 355.0 [(M)+]; mp 154° C.

Workup

  1. customwhile being purged with Argon
  2. additionPdCl2(PPh3)2 (100 mg, 1 mol %), PPh3 (37 mg, 1 mol %) and CuI (8 mg, 0.3 mol %) were added
  3. stirringStirring
  4. waitwas continued at 90° C. for 4.5 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-06415e11bb4f4e87bf7abc42fec49a35
Source dataset
uspto-grants-2007_07
Patent number
US07238808B2

Reaction notes

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