Triethylamine → HCID 67001155, compound

HRID 558573Notes

Reaction equation

HRID 558573 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH:14]([F:16])[F:15])[N:11]3[N:17]=[CH:18][C:19](I)=[C:10]3[N:9]=2)=[CH:4][C:3]=1[CH3:21].[CH3:22][Si:23]([C:26]#[CH:27])([CH3:25])[CH3:24].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]([CH:14]([F:16])[F:15])[N:11]3[N:17]=[CH:18][C:19]([C:27]#[C:26][Si:23]([CH3:25])([CH3:24])[CH3:22])=[C:10]3[N:9]=2)=[CH:4][C:3]=1[CH3:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 67001392HCID 67001392, compound

Product 1

HCID 67001155HCID 67001155, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(4-chloro-3-methyl-phenyl)-3-iodo-7-difluoromethyl-pyrazolo[1,5-a]pyrimidine (7.01 g, 16.7 mmol), trimethylsilylacetylene (4.16 mL, 30.0 mmol) and triethylamine (4.66 mL, 33.4 mmol) in N,N-dimethylformamide (18 mL) was stirred for 10 min at room temperature while being purged with Argon, then PdCl2(PPh3)2 (117 mg, 1 mol %), PPh3 (44 mg, 1 mol %) and CuI (10 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), evaporated and further purified by column chromatography on silica gel (dischloromethane/heptane 7:3) to give 5-(4-chloro-3-methyl-phenyl)-7-difluoromethyl-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (4.73 g, 73%) as an orange solid, which was dissolved in THF (74 mL) and MeOH (56 mL), while stirring at 0° C. potassium carbonate (168 mg, 1.22 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 (200 mL), dried (MgSO4) and evaporated. The crude product was further purified by flash chromatography on silica gel (heptane/EtOAc) followed by crystallization fromethyl acetate/hexane to give 5-(4-chloro-3-methyl-phenyl)-3-ethynyl-7-difluoromethyl-pyrazolo[1,5-a]pyrimidine (3.8 g, 72%) as a light brown solid. MS (EI) 317.2 [(M)+]; mp 143° C.

Workup

  1. customwhile being purged with Argon
  2. additionPdCl2(PPh3)2 (117 mg, 1 mol %), PPh3 (44 mg, 1 mol %) and CuI (10 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
  11. customfurther purified by column chromatography on silica gel (dischloromethane/heptane 7:3)

Sources & evidence

ORD record
ord-9239ad7bf1a24ae7ba9ad3d56f860f0d
Source dataset
uspto-grants-2011_11
Patent number
US08063048B2

Reaction notes

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