Potassium tert-butoxide → 4-((2-(Difluoromethyl)-1,3-thiazol-4-yl)methoxy)-1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203120Notes

Reaction equation

HRID 2203120 reaction equation
[F:1][CH:2]([F:10])[C:3]1[S:4][CH:5]=[C:6]([CH2:8][OH:9])[N:7]=1.Br[C:12]1[CH:17]=[CH:16][N:15]([C:18]2[CH:19]=[CH:20][C:21]3[N:25]=[C:24]([CH2:26][CH3:27])[N:23]([CH3:28])[C:22]=3[CH:29]=2)[C:14](=[O:30])[CH:13]=1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[F:1][CH:2]([F:10])[C:3]1[S:4][CH:5]=[C:6]([CH2:8][O:9][C:12]2[CH:17]=[CH:16][N:15]([C:18]3[CH:19]=[CH:20][C:21]4[N:25]=[C:24]([CH2:26][CH3:27])[N:23]([CH3:28])[C:22]=4[CH:29]=3)[C:14](=[O:30])[CH:13]=2)[N:7]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 89690005[2-(Difluoromethyl)-1,3-thiazol-4-yl]methanolHCID 1213862474-Bromo-1-(2-ethyl-1-methyl-1h-benzimidazol-6-yl)-2(1h)-pyridinone

Product 1

HCID 896912114-((2-(Difluoromethyl)-1,3-thiazol-4-yl)methoxy)-1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-oneYield 30.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of (2-(difluoromethyl)thiazol-4-yl)methanol (39 mg) and 4-bromo-1-(2-ethyl-1-methyl-1H-benzo[d]imidazol-6-yl)pyridin-2(1H)-one (52.3 mg) in toluene (1 ml) was added potassium tert-butoxide (35.3 mg) at 100° C. The mixture was stirred at 100° C. under dry atmosphere (CaCl2 tube) for 30 min. The mixture was quenched with water and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by recrystallization from EtOH-water to give the title compound (20.0 mg) as an off-white solid.

Workup

  1. dry with materialunder dry atmosphere (CaCl2 tube) for 30 min
  2. customThe mixture was quenched with water
  3. extractionextracted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with water and brine successively
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography (hexane/EtOAc
  9. customEtOAc/MeOH), followed by recrystallization from EtOH-water

Sources & evidence

ORD record
ord-f5c00e7221fd42198999652b66f4d2ba
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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