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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence