Ammonia → 1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-[(4-fluorobenzyl)oxy]pyridin-2(1H)-one

HRID 1497366Notes

Reaction equation

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

Participants

Conditions

Temperature: 150 °C

Procedure

To a suspension of 5-bromo-2-cyclopropyl-3-methyl-2H-indazole (2.0 g), 4-[(4-fluorobenzyl)oxy]pyridin-2(1H)-one (1.7 g) and potassium carbonate (3.3 g) in DMSO (20 ml) were added copper(I) iodide (1.5 g) and N,N′-dimethylethylenediamine (0.7 g), and the mixture was stirred at 150° C. for 3 hr. The reaction mixture was added to 28% aqueous ammonia, 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 (ethyl acetate/methanol) and recrystallized from ethyl acetate to give the title compound (2.17 g).

Workup

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 (ethyl acetate/methanol)
customrecrystallized from ethyl acetate

Sources & evidence

ORD record: ord-572be96743b240308feb2b9448324f9f
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199963B2

Reaction notes

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