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

HRID 1293650노트

반응식

HRID 1293650 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
23 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-507952ead39b4635ae0d91c5559995c2
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07238808B2

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