Tributylphosphine → 4-((4-Bromo-5-chloro-2-thienyl)methoxy)-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203059Notes

Reaction equation

HRID 2203059 reaction equation
C1CCN(C(/N=N/C(N2CCCCC2)=O)=O)CC1.[CH:19]1([C:22]2[N:26]([CH3:27])[C:25]3[CH:28]=[C:29]([N:32]4[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][C:33]4=[O:39])[CH:30]=[CH:31][C:24]=3[N:23]=2)[CH2:21][CH2:20]1.[Br:40][C:41]1[CH:42]=[C:43]([CH2:47]O)[S:44][C:45]=1[Cl:46].C(P(CCCC)CCCC)CCC>C1COCC1>[Br:40][C:41]1[CH:42]=[C:43]([CH2:47][O:38][C:35]2[CH:36]=[CH:37][N:32]([C:29]3[CH:30]=[CH:31][C:24]4[N:23]=[C:22]([CH:19]5[CH2:20][CH2:21]5)[N:26]([CH3:27])[C:25]=4[CH:28]=3)[C:33](=[O:39])[CH:34]=2)[S:44][C:45]=1[Cl:46]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 5702657diazenedicarboxylic acid bis(N,N-piperidide)HCID 18341112(4-Bromo-5-chlorothiophen-2-yl)methanolHCID 896910841-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896909604-((4-Bromo-5-chloro-2-thienyl)methoxy)-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-oneYield 6.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

1,1-(Azodicarbonyl)dipiperidine (269 mg) was added to a solution of 1-(2-cyclopropyl-1-methyl-1H-benzo[d]imidazol-6-yl)-4-hydroxypyridin-2(1H)-one (100 mg), (4-bromo-5-chloro-2-thienyl)methanol (162 mg) and tributylphosphine (0.26 ml) in THF (5 ml) at room temperature. The mixture was stirred at 60° C. for 2 h. The mixture was quenched with water at room temperature 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) and preparative HPLC (L-Column 2 ODS, eluted with H2O in acetonitrile containing 0.1% TFA). 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 (12 mg) as a white solid.

Workup

  1. customThe mixture was quenched with water at room temperature
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with water and brine successively
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (hexane/EtOAc) and preparative HPLC (L-Column 2 ODS, eluted with H2O in acetonitrile containing 0.1% TFA)
  8. extractionextracted with EtOAc
  9. customThe organic layer was separated
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-660c7dff026b415da425062052678154
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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