Water → 1-(2-Cyclopropyl-3-methyl-2H-indazole-5-yl)-4-[[5-(trifluoromethyl)-3-thienyl]methoxy]pyridine-2(1H)-one

HRID 1497409Notes

Reaction equation

HRID 1497409 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[S:7][CH:6]=[C:5]([CH2:8][OH:9])[CH:4]=1.CC(C)([O-])C.[K+].Cl[C:19]1[CH:24]=[CH:23][N:22]([C:25]2[CH:33]=[CH:32][C:31]3[C:27](=[C:28]([CH3:37])[N:29]([CH:34]4[CH2:36][CH2:35]4)[N:30]=3)[CH:26]=2)[C:21](=[O:38])[CH:20]=1.O>CC(N(C)C)=O>[CH:34]1([N:29]2[C:28]([CH3:37])=[C:27]3[C:31]([CH:32]=[CH:33][C:25]([N:22]4[CH:23]=[CH:24][C:19]([O:9][CH2:8][C:5]5[CH:4]=[C:3]([C:2]([F:10])([F:1])[F:11])[S:7][CH:6]=5)=[CH:20][C:21]4=[O:38])=[CH:26]3)=[N:30]2)[CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 962WaterHCID 199573935-(Trifluoromethyl)-3-thiophenemethanolHCID 23665647Potassium tert-butoxideHCID 1177986084-chloro-1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one

Product 1

HCID 904694371-(2-Cyclopropyl-3-methyl-2H-indazole-5-yl)-4-[[5-(trifluoromethyl)-3-thienyl]methoxy]pyridine-2(1H)-oneYield 83.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of [5-(trifluoromethyl)thiophen-3-yl]methanol (100 g) in DMA (1363 ml) was added potassium tert-butoxide (61.3 g) at 5° C., and the mixture was stirred at the same temperature for 30 min. To the obtained mixture was added 4-chloro-1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)pyridin-2(1H)-one (136.5 g), and the mixture was stirred at an inside temperature of 70° C. for 1.5 hr. The reaction mixture was cooled to room temperature, water (1.4 L) was added, and the obtained suspension was stirred overnight. The precipitated solid was collected by filtration, and washed with water (2.8 L), ethanol (540 ml) and diisopropyl ether (500 ml) to give the title compound (168.6 g).

Workup

  1. stirringthe mixture was stirred at an inside temperature of 70° C. for 1.5 hr
  2. stirringthe obtained suspension was stirred overnight
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed with water (2.8 L), ethanol (540 ml) and diisopropyl ether (500 ml)

Sources & evidence

ORD record
ord-240e8396b5f74923b39faa80eca19cee
Source dataset
uspto-grants-2015_12
Patent number
US09199963B2

Reaction notes

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