Water → 1-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((4-(trifluoromethyl)-2-thienyl)methoxy)pyridin-2(1H)-one

HRID 2203102Notes

Reaction equation

HRID 2203102 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH2:8][OH:9])[S:6][CH:7]=1.[H-].[Na+].Br[C:15]1[CH:20]=[CH:19][N:18]([C:21]2[CH:22]=[CH:23][C:24]3[N:28]=[C:27]([CH:29]4[CH2:31][CH2:30]4)[N:26]([CH3:32])[C:25]=3[CH:33]=2)[C:17](=[O:34])[CH:16]=1.O>CC(N(C)C)=O>[CH:29]1([C:27]2[N:26]([CH3:32])[C:25]3[CH:33]=[C:21]([N:18]4[CH:19]=[CH:20][C:15]([O:9][CH2:8][C:5]5[S:6][CH:7]=[C:3]([C:2]([F:10])([F:1])[F:11])[CH:4]=5)=[CH:16][C:17]4=[O:34])[CH:22]=[CH:23][C:24]=3[N:28]=2)[CH2:30][CH2:31]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 896902462-Thiophenemethanol, 4-(trifluoromethyl)-HCID 896908634-Bromo-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

Product 1

HCID 896909571-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((4-(trifluoromethyl)-2-thienyl)methoxy)pyridin-2(1H)-oneYield 15%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (4-(trifluoromethyl)thiophen-2-yl)methanol (50 mg) in DMA (2 ml) was added NaH (60% in oil, 18.3 mg) at room temperature, and the mixture was stirred for 30 min. 4-Bromo-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (79 mg) was added to the mixture, and the mixture was heated at 120° C. for 30 min under microwave irradiation. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed with saturated NaHCO3 solution and brine successively, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/MeOH), followed by crystallized from hot EtOAc to give the title compound (15.3 mg) as pale yellow crystals.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with saturated NaHCO3 solution and brine successively
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (EtOAc/MeOH)
  7. customby crystallized from hot EtOAc

Sources & evidence

ORD record
ord-a668cd8036fd42ba93d3cc905545f5c3
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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