5-bromo-1-(4-fluorophenyl)-1H-indazole → 1-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carbonitrile

HRID 244442노트

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HRID 244442 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[Li]CCCC.[CH2:23]([N:26]1[CH:30]=[C:29]([C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])[CH:28]=[C:27]1[C:37]#[N:38])[CH:24]=[CH2:25]>C1COCC1>[CH2:23]([N:26]1[CH:30]=[C:29]([C:31]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:6]=[CH:5]3)([OH:36])[C:32]([F:35])([F:33])[F:34])[CH:28]=[C:27]1[C:37]#[N:38])[CH:24]=[CH2:25]

참가 물질

5

반응물 3

HCID 468307945-bromo-1-(4-fluorophenyl)-1H-indazoleHCID 594372991-allyl-4-(2,2,2-trifluoro-acetyl)-1H-pyrrole-2-carbonitrileHCID 178418339Butyllithium

생성물 1

HCID 594372451-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carbonitrile수율 67%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a chilled (−78° C.) solution of 5-bromo-1-(4-fluorophenyl)-1H-indazole (1.3 g, 4.3 mmol, 1.1 equiv.) in 20 mL of THF was added n-BuLi (2.5 M in hexanes, 1.7 ml, 4.3 mmol, 1.1 equiv.) followed by a chilled (−78° C.) solution of 1-allyl-4-(2,2,2-trifluoroacetyl)-1H-pyrrole-2-carbonitrile (0.9 g, 3.9 mmol, 1 equiv.) in 3 mL of THF. After 30 minutes, the mixture was warmed to 0° C., quenched with water, diluted with brine, and extracted with EtOAc. The combined organics were dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using EtOAc-hexanes (5-30% gradient) to afford 1.15 g (66%) of the title compound as an off-white solid. MS m/z 441.26 (MH+).

후처리

  1. customquenched with water
  2. additiondiluted with brine
  3. extractionextracted with EtOAc
  4. customThe combined organics were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-dd13b837909b47d59d23bb7d4a3259bb
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658637B2

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