1-(Methoxymethyl)benzoimidazole → {3-[5-Fluoro-3-(tetrahydro-pyran-4-YL)-pyridin-2-yloxy]-cyclobutyl}-(1-methoxymethyl-1H-benzoimidazol-2-YL)-methanone

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(methoxymethyl)-1H-benzo[d]imidazole (1.5 g, 9.04 mmol) in THF (20 mL) at −78° C. was added butyllithium (2.5 M in hexane) (3.7 mL, 9.16 mmol). The solution was stirred at −78° C. for 30 min and a solution of 3-[5-fluoro-3-(tetrahydro-pyran-4-yl)-pyridin-2-yloxy]-cyclobutanecarboxylic acid methoxy-methyl-amide (2.2 g, 6.87 mmol) in THF (20 mL) was added dropwise via cannula. The reaction mixture was stirred at −78° C. for 30 min and then warmed to RT and quenched with water. The reaction mixture was extracted with EtOAc (3×25 mL) and the organic phases were combined and washed with water (1×10 mL), brine (1×10 mL), dried over MgSO4, filtered, and concentrated to get a residue, which was purified by flash column chromatography on silica gel (10% to 60% EtOAc in hexanes) to give the product (1.2 g) as yellow oil.

Provenance & Evidence