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

HRID 1497381Notes

Reaction equation

HRID 1497381 reaction equation
[CH3:1][N:2]1[C:10]([CH3:11])=[C:9]2[C:4]([CH:5]=[CH:6][C:7]([N:12]3[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:13]3=[O:19])=[CH:8]2)=[N:3]1.[F:20][C:21]([F:30])([F:29])[C:22]1[S:26][CH:25]=[C:24]([CH2:27]O)[CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>O1CCCC1>[CH3:1][N:2]1[C:10]([CH3:11])=[C:9]2[C:4]([CH:5]=[CH:6][C:7]([N:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:27][C:24]4[CH:23]=[C:22]([C:21]([F:30])([F:29])[F:20])[S:26][CH:25]=4)=[CH:14][C:13]3=[O:19])=[CH:8]2)=[N:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 199573935-(Trifluoromethyl)-3-thiophenemethanolHCID 1177986701-(2,3-dimethyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 1177986711-(2,3-dimethyl-2H-indazol-5-yl)-4-{[5-(trifluoromethyl)thiophen-3-yl]methoxy}pyridin-2(1H)-oneYield 42.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-(2,3-dimethyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one (50 mg), [5-(trifluoromethyl)thiophen-3-yl]methanol (71 mg) and triphenylphosphine (154 mg) in tetrahydrofuran (5 ml) was added bis(2-methoxyethyl)azodicarboxylate (138 mg) at room temperature, and the mixture was stirred at the same temperature for 3 hr. To the reaction mixture was added water, 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 (hexane/ethyl acetate/methanol) and recrystallized from ethanol-hexane to give the title compound (35 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate/methanol)
  6. customrecrystallized from ethanol-hexane

Sources & evidence

ORD record
ord-7c1ddbcf47f04468b772835341c86254
Source dataset
uspto-grants-2015_12
Patent number
US09199963B2

Reaction notes

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