Water → 1-(2-ethyl-3-methyl-2H-indazol-5-yl)-4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]methoxy}pyridin-2(1H)-one

HRID 1497400Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:16]=[CH:15][C:14]3[C:10](=[C:11]([CH3:19])[N:12]([CH2:17][CH3:18])[N:13]=3)[CH:9]=2)[C:4](=[O:20])[CH:3]=1.[F:21][C:22]([F:31])([F:30])[C:23]1[N:24]=[C:25]([CH2:28][OH:29])[S:26][CH:27]=1.CC(C)([O-])C.[K+].O>C1(C)C=CC=CC=1>[CH2:17]([N:12]1[C:11]([CH3:19])=[C:10]2[C:14]([CH:15]=[CH:16][C:8]([N:5]3[CH:6]=[CH:7][C:2]([O:29][CH2:28][C:25]4[S:26][CH:27]=[C:23]([C:22]([F:31])([F:30])[F:21])[N:24]=4)=[CH:3][C:4]3=[O:20])=[CH:9]2)=[N:13]1)[CH3:18]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-bromo-1-(2-ethyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one (350 mg) and [4-(trifluoromethyl)-1,3-thiazol-2-yl]methanol (289 mg) in toluene (5 ml) was added potassium tert-butoxide (355 mg) at room temperature, and the mixture was stirred at 100° C. for 2 hr. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) and recrystallized from ethanol-water to give the title compound (75 mg).

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)
customrecrystallized from ethanol-water

Sources & evidence

ORD record: ord-f27d285c2ba840889d1719219c3bfce4
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199963B2

Reaction notes

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