Hydrochloric Acid → HCID 67408688, compound

Participants

Reaction Conditions

Reaction Steps

A 10 mL flask was charged with ethyl 4-{[1-(biphenyl-4-ylmethyl)-4,6-difluoro-5-(1H-indol-5-yl)-1H-benzimidazol-2-yl]oxy}cyclohexanecarboxylate (0.080 g, 0.132 mmol), DMAP (0.048 g, 0.396 mmol), cyclopropylboronic acid (0.023 g, 0.264 mmol), and Cu(OAc)2 (4.8 mg, 0.026 mmol) under a nitrogen atmosphere. Toluene (1.3 mL) was added and the resulting suspension was treated with a 0.6 M solution of NaHMDS in toluene (0.220 mL, 0.132 mmol) dropwise via syringe. Dry air was purged into the reaction vessel, and the reaction was heated at 95° C. overnight. The dark reaction mixture was then cooled to ambient temperature and treated with 20 mL of 1 N HCl. The aqueous layer was separated and extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. Purification of the resulting crude residue by preparative TLC (25% EtOAc/hexanes) furnished the title compound as a pale yellow residue. LCMS: calculated for C40H37F2N3O3 645.74, observed rule 646.2 (M+H)+ (Rt 3.03/4 min).

Provenance & Evidence