Sodium Hydroxide → 8-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 8-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (200 mg, 0.49 mmol) in IMS (10 mL) was added a 1.0 M aqueous solution of sodium hydroxide (1.0 mL, 1.0 mmol). The reaction mixture was heated at 65° C. for 2 hours and then cooled to room temperature and concentrated in vacuo. The resulting residue was azeotroped with toluene, and then suspended in THF (10 mL). O-(2-Vinyloxy-ethyl)-hydroxylamine (103 mg, 1.0 mmol), N-N-diisopropylethylamine (0.34 mL, 1.96 mmol), EDCI (192 mg, 1.0 mmol) and HOBt (135 mg, 1.0 mmol) were then added sequentially before the reaction mixture was stirred 18 hours at room temperature. The reaction mixture was then diluted with ethyl acetate and washed with water followed by a saturated aqueous solution of sodium bicarbonate and then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl acetate in dichloromethane) to afford the title compound as a pale yellow oil (151 mg, 64%). LCMS (method B): RT=3.05 min, [M+H]+=483.

Provenance & Evidence