Potassium Carbonate → 1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-{[4-(trifluoromethyl)thiophen-2-yl]methoxy}pyridin-2(1H)-one

HRID 1497407Notes

Reaction equation

HRID 1497407 reaction equation
[CH:1]1([N:4]2[C:12]([CH3:13])=[C:11]3[C:6]([CH:7]=[CH:8][C:9]([N:14]4[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]4=[O:21])=[CH:10]3)=[N:5]2)[CH2:3][CH2:2]1.Cl[CH2:23][C:24]1[S:25][CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([N:4]2[C:12]([CH3:13])=[C:11]3[C:6]([CH:7]=[CH:8][C:9]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:23][C:24]5[S:25][CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=5)=[CH:16][C:15]4=[O:21])=[CH:10]3)=[N:5]2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1177986592-(Chloromethyl)-4-(trifluoromethyl)thiopheneHCID 1177986831-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 1177986871-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-{[4-(trifluoromethyl)thiophen-2-yl]methoxy}pyridin-2(1H)-oneYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-hydroxypyridin-2(1H)-one (200 mg) and 2-(chloromethyl)-4-(trifluoromethyl)thiophene (171 mg) in DMF (4 ml) was added potassium carbonate (118 mg) at room temperature, and the mixture was stirred at the same temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was fractionated by HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% NH4HCO3)), and saturated aqueous sodium hydrogen carbonate solution was added to the obtained fraction. The mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from methanol-water to give the title compound (152 mg).

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionwas added to the obtained fraction
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was crystallized from methanol-water

Sources & evidence

ORD record
ord-104550d862bb43c68ef62b21047e9320
Source dataset
uspto-grants-2015_12
Patent number
US09199963B2

Reaction notes

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