Acetoxyacetic acid → N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

Carbonyl diimidazole (CDI) (324 mg, 2.0 mmol) was added to a stirred solution of 2-acetoxyacetic acid (236 mg, 2.0 mmol) in NMP. After 20 minutes, N-(5-(N′-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (9) (310 mg, 1.0 mmol) was added in one portion and the resulting solution was stirred for 1 hour before it was heated at 125° C. for 15 minutes in a microwave reactor. The reaction solution was subjected to standard aqueous work up to afford a residue which was hydrolyzed by lithium hydroxide monohydrate (252 mg, 6.0 mmol) in THF/MeOH/H2O (3:2:1). After removal of all solvents 2M NaHCO3 (10 mL) was added. The precipitate was filtered and dried in air to afford N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (43). 1H NMR (400 MHz, d6-DMSO) δ 10.02 (s, 1H), 9.46 (d, J=6.8 Hz, 1H), 8.59 (s, 1H), 8.11 (s, 1H), 7.82 (m, 2H), 7.53 (m, 2H), 7.18 (m, 1H), 6.08 (m, 1H), 4.80 (d, J=6.0 Hz, 2H), 2.37 (s, 3H). MS m/z 350.1 (M+1)+.

Provenance & Evidence