Tributylphosphine → 1-(1,2-Dimethyl-1H-benzimidazol-6-yl)-4-((5-(trifluoromethyl)thiophen-3-yl)methoxy)pyridin-2(1H)-one

HRID 2203122Notes

Reaction equation

HRID 2203122 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[S:26][CH:25]=[C:24]([CH2:27]O)[CH:23]=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[CH:23]=[C:22]([C:21]([F:30])([F:29])[F:20])[S:26][CH:25]=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 199573935-(Trifluoromethyl)-3-thiophenemethanolHCID 896909671-(1,2-Dimethyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896913081-(1,2-Dimethyl-1H-benzimidazol-6-yl)-4-((5-(trifluoromethyl)thiophen-3-yl)methoxy)pyridin-2(1H)-oneYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 1-(1,2-dimethyl-1H-benzo[d]imidazol-6-yl)-4-hydroxypyridin-2(1H)-one (100 mg) in THF (5 ml) were added (5-(trifluoromethyl)thiophen-3-yl)methanol (78 mg), 1,1′-(azodicarbonyl)dipiperidine (128 mg) and tributylphosphine (0.13 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). The same reaction was conducted, and the combined products were purified 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 a white solid.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was purified by NH silica gel column chromatography (EtOAc/MeOH)
  3. customThe same reaction
  4. customthe combined products were purified by preparative HPLC (C18, mobile phase: H2O/CH3CN (0.1% TFA included))
  5. extractionextracted with EtOAc
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0b2e225bac984edda1d121c22846798c
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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