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

To a chilled (−78° C.) solution of 1-allyl-4-bromo-1H-pyrazole-3-carbonitrile (116 mg, 0.550 mmol) in dry THF (2 mL) was added lithium diisopropylamide (367 μL, 1.5 M solution in hexanes, 0.55 mmol). After 5 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 2 mL of THF 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 10 mL of brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on SiO2 (0-50% ethyl acetate in hexanes, gradient) to afford 213 mg (82%) of the title product. MS m/z 520.19/522.20 (M+).

1. additionwas added
2. waitAfter 15 minutes
3. customquenched with 10 mL of saturated aqueous sodium bicarbonate
4. extractionextracted with three 10 mL portions of ethyl ether
5. washThe combined organic layers were washed with 10 mL of brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was chromatographed on SiO2 (0-50% ethyl acetate in hexanes, gradient)

ORD record

ord-7afe47646cf64829ab7482b98245c369

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658637B2