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

HRID 558540Notes

Reaction equation

HRID 558540 reaction equation
Br[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][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)=[N:7][C:6]=12.[CH3:25][Si:26]([C:29]#[CH:30])([CH3:28])[CH3:27].CCN(CC)CC>C1COCC1>[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][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 715396793-Bromo-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine

Product 1

HCID 715397337-Trifluoromethyl-5-(4-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of 3-bromo-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (Example C.1 step 2a) (12.30 g, 30 mmol), trimethylsilylacetylene (8.3 mL, 60 mmol) and Et3N (6.3 mL, 45 mmol) in THF (30 mL) was stirred for 10 min at 23° C. while being purged with Argon, then PdCl2(PPh3)2 (105 mg, 0.5 mol %), PPh3 (20 mg, 0.25 mol %) and CuI (17 mg, 0.3 mol %) were added. Stirring was continued at 75° C. for 38 h. After 22 h, trimethylsilylacetylene (2.1 mL) and Et3N (2.1 mL) was added. Cooled to 23° C., diluted with ethyl acetate (100 mL), filtered through celite, washed with ethyl acetate. Removal of the solvent in vacuum left the 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (13.65 g, 106%) as an orange solid, which can directly be used in the subsequent step. An analytical sample was obtained by silica gel column chromatography with heptane/EtOAc. MS (ISP) 427.0 [(M)+]; mp 136° C.

Workup

  1. customwhile being purged with Argon
  2. additionPdCl2(PPh3)2 (105 mg, 0.5 mol %), PPh3 (20 mg, 0.25 mol %) and CuI (17 mg, 0.3 mol %) were added
  3. stirringStirring
  4. waitwas continued at 75° C. for 38 h
  5. waitAfter 22 h
  6. additiontrimethylsilylacetylene (2.1 mL) and Et3N (2.1 mL) was added
  7. temperatureCooled to 23° C.
  8. additiondiluted with ethyl acetate (100 mL)
  9. filtrationfiltered through celite
  10. washwashed with ethyl acetate
  11. customRemoval of the solvent in vacuum
  12. waitleft the 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-3-trimethylsilanylethynyl-pyrazolo[1,5-a]pyrimidine (13.65 g, 106%) as an orange solid, which
  13. customAn analytical sample was obtained by silica gel column chromatography with heptane/EtOAc

Sources & evidence

ORD record
ord-7a07a9ab14764f68ba18101be82bbc2a
Source dataset
uspto-grants-2011_11
Patent number
US08063048B2

Reaction notes

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