Triethylamine → HCID 67000937, compound

HRID 1293679Notes

Reaction equation

HRID 1293679 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]2[C:10]([CH:11]([F:13])[F:12])=[CH:9][C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:7][C:6]=12.[CH3:24][Si:25]([C:28]#[CH:29])([CH3:27])[CH3:26].C(N(CC)CC)C>CN(C)C=O>[F:12][CH:11]([F:13])[C:10]1[N:5]2[N:4]=[CH:3][C:2]([C:29]#[C:28][Si:25]([CH3:27])([CH3:26])[CH3:24])=[C:6]2[N:7]=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 67000882HCID 67000882, compound

Product 1

HCID 67000937HCID 67000937, compoundYield 113.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-iodo-7-difluoromethyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (8.23 g, 18.7 mmol), trimethylsilylacetylene (4.67 mL, 33.7 mmol) and triethylamine (5.22 mL, 37.5 mmol) in N,N-dimethylformamide (20 mL) was stirred for 10 min at room temperature while being purged with Argon, then PdCl2(PPh3)2 (132 mg, 1 mol %), PPh3 (49 mg, 1 mol %) and CuI (11 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 water (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water (2×50 mL) and brine (70 mL), dried (MgSO4) and evaporated to give 7-difluoromethyl-5-(3-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (8.68 g) as a light brown solid, which was dissolved in THF (42 mL) and MeOH (98 mL), while stirring at 0° C. potassium carbonate (293 mg, 2 mmol) was added and the mixture was stirred at 0° C. for 5 h. The mixture was diluted with ice water (150 mL) and extracted with TBME (3×200 mL). The combined organic layers were washed with brine (100 mL), dried (MgSO4) and evaporated. The crude product was further purified by silica gel column chromatography (heptane/EtOAc 4:1) followed by trituration with heptane to give 7-difluoromethyl-3-ethynyl-5-(3-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (4.34 g, 61%) as an orange solid. MS (EI) 337.1 [(M)+]; mp 149° C.

Workup

  1. customwhile being purged with Argon
  2. additionPdCl2(PPh3)2 (132 mg, 1 mol %), PPh3 (49 mg, 1 mol %) and CuI (11 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 water (100 mL)
  7. extractionextracted with ethyl acetate (2×100 mL)
  8. washThe combined organic layers were washed with water (2×50 mL) and brine (70 mL)
  9. dry with materialdried (MgSO4)
  10. customevaporated

Sources & evidence

ORD record
ord-22c1e306376e466fb4fde310abad8502
Source dataset
uspto-grants-2007_07
Patent number
US07238808B2

Reaction notes

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