Tributylphosphine → 1-(2-Cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-4-[(2-methyl-3-thienyl)methoxy]-2(1h)-pyridinone

HRID 2203041Notes

Reaction equation

HRID 2203041 reaction equation
[CH3:1][C:2]1[S:6][CH:5]=[C:4]([CH2:7][OH:8])[CH:3]=1.[CH:9]1([C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[C:19]([N:22]4[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][C:23]4=[O:29])[CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:11][CH2:10]1.[CH2:30](P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH:9]1([C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[C:19]([N:22]4[CH:27]=[CH:26][C:25]([O:8][CH2:7][C:4]5[CH:3]=[C:2]([CH3:1])[S:6][CH:5]=5)=[CH:24][C:23]4=[O:29])[CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:10][CH2:11]1.[CH:9]1([C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[C:19]([N:22]4[CH:27]=[CH:26][C:25]([O:28][CH2:7][C:4]5[CH:3]=[CH:2][S:6][C:5]=5[CH3:30])=[CH:24][C:23]4=[O:29])[CH:20]=[CH:21][C:14]=3[N:13]=2)[CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 158517765-methyl-3-ThiophenemethanolHCID 896910841-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 2

HCID 896910941-(2-Cyclopropyl-1-methyl-1h-benzimidazol-6-yl)-4-[(2-methyl-3-thienyl)methoxy]-2(1h)-pyridinoneHCID 89691147HCID 89691147, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (5-methyl-3-thienyl)methanol (72 mg), 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (100 mg), tributylphosphine (0.264 ml), 1,1′-(azodicarbonyl)dipiperidine (269 mg) and THF (10 ml) was stirred at 60° C. for 3 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with brine, dried with MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by NH silica gel column chromatography (hexane/EtOAc) to give the title compound as a mixture with 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((2-methyl-3-thienyl)methoxy)pyridin-2(1H)-one. This mixture was subjected to HPLC separation (C18, mobile phase: H2O/CH3CN (0.1% TFA included)). The solution was neutralized with saturated Na2CO3 solution and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, filtered through a plug of silica gel and concentrated in vacuo. The resulting solid was recrystallized from EtOH to give the title compound (15.8 mg) as an off-white solid.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washthe organic layer was washed with brine
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (hexane/EtOAc

Sources & evidence

ORD record
ord-3f67eac4ffba4a299e5d64d99e79c223
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

Loading…