2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone → 1-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrazole-3-carbonitrile

HRID 244479Notes

Reaction equation

HRID 244479 reaction equation
[CH2:1]([N:4]1[CH:8]=[C:7](Br)[C:6]([C:10]#[N:11])=[N:5]1)[CH:2]=[CH2:3].[Li]CCCC.[F:17][C:18]([F:38])([F:37])[C:19]([C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[N:25]=[CH:24]2)=[O:20]>CCOCC.C1COCC1>[CH2:1]([N:4]1[CH:8]=[C:7]([C:19]([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[N:25]=[CH:24]3)([OH:20])[C:18]([F:37])([F:17])[F:38])[C:6]([C:10]#[N:11])=[N:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanoneHCID 594372421-allyl-4-bromo-1H-pyrazole-3-carbonitrileHCID 178418339Butyllithium

Product 1

HCID 594372031-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrazole-3-carbonitrileYield 69%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a chilled (−78° C.) solution of 1-allyl-4-bromo-1H-pyrazole-3-carbonitrile (116.6 mg, 0.550 mmol) in dry ether (2 mL) was added n-BuLi (190 pt, 2.5 M in hexanes, 0.475 mmol). After 2 minutes a chilled (−78° C.) solution of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone (154 mg, 0.500 mmol) in THF (2 mL) was added. After 15 minutes, the mixture was warmed to room temperature, quenched with 10 mL of saturated aqueous sodium bicarbonate and extracted with three 10 mL portions of ethyl ether. The combined organic layers were washed with brine (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by chromatography on SiO2 (0-50% ethyl acetate in hexanes, gradient) to give 152 mg (69%) of the title compound. MS m/z 422.96 (MH+).

Workup

  1. additionwas added
  2. customquenched with 10 mL of saturated aqueous sodium bicarbonate
  3. extractionextracted with three 10 mL portions of ethyl ether
  4. washThe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on SiO2 (0-50% ethyl acetate in hexanes, gradient)

Sources & evidence

ORD record
ord-77e6588979264c85acb10d6c046bb950
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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