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 244442Notes

Reaction equation

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]

Participants

Conditions

Temperature: 0 °C

Procedure

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+).

Workup

customquenched with water
additiondiluted with brine
extractionextracted with EtOAc
customThe combined organics were dried
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography

Sources & evidence

ORD record: ord-dd13b837909b47d59d23bb7d4a3259bb
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658637B2

Reaction notes

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