Sodium hydride → 2-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrile

HRID 1875394노트

반응식

HRID 1875394 반응식
[H-].[Na+].[CH3:3][C:4]1([CH3:18])[CH2:12][C:11]2[NH:10][N:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[C:7]=2[C:6](=[O:17])[CH2:5]1.[Br:19][C:20]1[CH:27]=[C:26](F)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]>CS(C)=O>[Br:19][C:20]1[CH:27]=[C:26]([N:10]2[C:11]3[CH2:12][C:4]([CH3:18])([CH3:3])[CH2:5][C:6](=[O:17])[C:7]=3[C:8]([C:13]([F:16])([F:15])[F:14])=[N:9]2)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 1189392-Bromo-4-fluorobenzonitrileHCID 441904636,6-Dimethyl-3-(trifluoromethyl)-1,5,6,7-tetrahydro-4H-indazol-4-one

생성물 1

HCID 118541752-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrile수율 63.2%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
45 °C

실험 절차

Sodium hydride (168 mg, 7.02 mmol, 1.0 eq.) was added to a solution of 6,6-dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one (1.63 g, 7.02 mmol, 1.0 eq.) in 35 mL of anhydrous dimethyl sulfoxide. After 15 min 2-bromo-4-fluorobenzonitrile (2.25 g, 11.23 mmol, 1.6 eq.) was added as a solid. The reaction mixture was heated at 45° C. After 23 h the reaction mixture was cooled to ambient temperature and quenched with 10 mL of saturated aqueous ammonium chloride. The mixture was diluted with water and extracted with ethyl acetate (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified on a Biotage (SiO2, hexanes-ethyl acetate) to afford 2-bromo-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (1.83 g, 63%) as an off-white powder, LC/MS: (M+H)=412.0.

후처리

  1. temperatureAfter 23 h the reaction mixture was cooled to ambient temperature
  2. customquenched with 10 mL of saturated aqueous ammonium chloride
  3. additionThe mixture was diluted with water
  4. extractionextracted with ethyl acetate (4×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on a Biotage (SiO2, hexanes-ethyl acetate)

출처 및 근거

ORD 기록
ord-46e5244599604f1f81d2134ea86b623d
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309548B2

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