6-bromo-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine → Benzyl 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)benzoate

Participants

Reaction Steps

A mixture of 6-bromo-N-(3,4-dimethoxyphenyl)imidazo[1,2-a]pyrazin-8-amine (1.82 g, 5.22 mmol) and benzyl 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamido)benzoate (3.06 g, 5.22 mmol, 78% by mass) in 1 M aqueous sodium carbonate (8 mL) and 1,4-dioxane (24 mL) was sparged with nitrogen with stirring for 5 min. The resulting mixture was treated with tetrakis(triphenylphosphine)palladium(0) (1.20 g, 1.04 mmol) and stirred at reflux for 2.5 h. After this time, the reaction was cooled to ambient temperature, diluted with ethyl acetate (100 mL) and washed with brine (100 mL). The aqueous layer was extracted with ethyl acetate (100 mL) and the combined organic layers were dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue obtained was purified by chromatography (silica, methylene chloride to 1:4 ethyl acetate/methylene chloride) to afford benzyl 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)benzoate (2.02 g, 65%) as an off-white solid: mp 154-160° C.; 1H NMR (300 MHz, CDCl3) δ 10.72 (s, 1H), 9.57 (s, 1H), 8.74 (s, 1H), 8.57 (s, 1H), 8.25 (d, J=7.8 Hz, 1H), 8.08-7.94 (m, 7H), 7.69-7.60 (m, 3H), 7.50-7.34 (m, 5H), 6.92 (d, J=8.7 Hz, 1H), 5.36 (s, 2H), 3.78 (s, 3H), 3.73 (s, 3H); ESI MS m/z 600 [M+H]+; HPLC, 8.93 min, 95.9% (AUC).

Provenance & Evidence