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

HRID 268978ノート

反応式

HRID 268978 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
23 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0c23862078e44162bf5979bb12c46b6c
出典データセット
uspto-grants-2008_11
特許番号
US07446113B2

反応ノート

読み込み中…