Hydroxylamine → 8-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 8-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (68 mg, 0.21 mmol) in IMS (2.5 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.25 mL, 0.25 mmol). The reaction mixture was heated at 65° C. for 1 hour and then cooled to room temperature and concentrated in vacuo. The resulting residue was azeotroped with toluene, and then suspended in THF (4 mL). 042-Vinyloxy-ethyl)-hydroxylamine (43 mg, 0.42 mmol), N-N-diisopropylethylamine (0.14 mL, 0.84 mmol), EDCI (81 mg, 0.42 mmol) and HOBt (57 mg, 0.42 mmol) were then added sequentially, before the reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was then diluted with ethyl acetate and washed with water, a saturated aqueous solution of sodium bicarbonate and brine before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 5%, methanol in dichloromethane) to afford the title compound as a pale yellow oil (56 mg, 67%). LCMS (method B): RT=3.02 min, [M+H]+=397.

Provenance & Evidence