Tributylphosphine → 1-(1,2-Dimethyl-1H-benzimidazol-6-yl)-4-((4-(trifluoromethyl)thiophen-2-yl)methoxy)pyridin-2(1H)-one

HRID 2203115Notes

Reaction equation

HRID 2203115 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]3=[O:18])[CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH3:19].[F:20][C:21]([F:30])([F:29])[C:22]1[CH:23]=[C:24]([CH2:27]O)[S:25][CH:26]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C1COCC1>[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([N:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:27][C:24]4[S:25][CH:26]=[C:22]([C:21]([F:30])([F:29])[F:20])[CH:23]=4)=[CH:13][C:12]3=[O:18])[CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[CH3:19]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 896902462-Thiophenemethanol, 4-(trifluoromethyl)-HCID 896909671-(1,2-Dimethyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 897026681-(1,2-Dimethyl-1H-benzimidazol-6-yl)-4-((4-(trifluoromethyl)thiophen-2-yl)methoxy)pyridin-2(1H)-oneYield 39.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 1-(1,2-dimethyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (200 mg) in THF (5 ml) were added (4-(trifluoromethyl)thiophen-2-yl)methanol (157 mg), 1,1′-(azodicarbonyl)dipiperidine (257 mg) and tributylphosphine (0.25 ml) at room temperature, and the mixture was stirred at 50° C. overnight. After cooling, the mixture was purified by NH silica gel column chromatography (EtOAc/MeOH), followed by preparative HPLC (C18, mobile phase: H2O/CH3CN (0.1% TFA included)). The desired fraction was neutralized with saturated NaHCO3 solution, and extracted with EtOAc. The organic layer was separated, dried over MgSO4 and concentrated in vacuo to give the title compound (129 mg) as white crystals.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was purified by NH silica gel column chromatography (EtOAc/MeOH)
  3. extractionextracted with EtOAc
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-11fe7d36c22d4aeca6e6408b17f3a5b6
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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