A solution of benzene-1,2-diamine (175 mg, 1618 μmol), triethyl orthoformate (665 μL, 4353 μmol), and benzenesulfonic acid (10 mg, 65 μmol) in toluene (1.6 mL) was heated to reflux for 4 h and then slowly distilled to remove half of the solvent. The mixture was then cooled to RT and neutralized with diisopropyl amine, followed by addition of a solution of ethyl 4-(3-(trifluoromethyl)pyridin-2-yloxy)benzoate (554 mg, 1780 μmol) in 1.7 mL of THF. The mixture was cooled to −78° C. and 1.2 equiv of LDA (0.971 mL, 2.0M) was added. After aging at −78° C. for 1.5 h, the mixture was warmed to RT and stirred for 1.5 h and then 2N HCl was added and the mixture was agitated for 15 min. Following that, the mixture was adjusted to pH 9 with 1N NaOH. Ethyl acetate was added and the layers were separated, the aqueous was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Following purification, (1H-benzo[d]imidazol-2-yl)(4-(3-(trifluoromethyl)pyridin-2-yloxy)phenyl)methanone was obtained. MS (ESI, pos. ion) m/z: 384 (M+1). IC50 (uM) +++++.
