Potassium Phosphate, Tribasic → 8-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (105 mg, 0.50 mmol), 4-cyclopropyl-2-fluoroaniline (101 mg, 0.60 mmol), Pd2dba3 (18 mg, 0.02 mmol), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (37 mg, 0.08 mmol) and K3PO4 (148 mg, 0.70 mmol) in toluene (2 mL) was degassed and then heated to 100° C. for 24 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate. The resultant solution was washed with water and brine, then loaded onto a 10 g Isolute® SCX-2 cartridge which was eluted with methanol followed by a 2M solution of ammonia in methanol. The appropriate fractions were combined and concentrated. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 10%, ethyl acetate in dichloromethane) to afford the title compound as a yellow oil (68 mg, 42%). LCMS (method B): RT=3.45 min, [M+H]+=326.

Provenance & Evidence