4-Methylmorpholine → Methyl 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)-3-methylbenzoate

Participants

Reaction Steps

A mixture of 3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzoic acid hydrochloride salt (80 mg, 0.187 mmol), methyl 4-amino-3-methylbenzoate (46 mg, 0.281 mmol), benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (124 mg, 0.281 mmol) and 4-methylmorpholine (95 mg, 0.937 mmol) in DMF (1.5 mL) was stirred at ambient temperature for 18 h. The mixture was then stirred at 45° C. for 6 h before additional methyl 4-amino-3-methylbenzoate (46 mg, 0.281 mmol) was added and the resulting mixture was stirred at ambient temperature for 18 h. To the reaction mixture was added (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (97 mg, 0.187 mmol) and the resulting mixture was stirred at 45° C. for 18 h and then at ambient temperature for 6 d. After this time, the reaction was diluted with ethyl acetate (50 mL) and washed with water (30 mL) then 5% aqueous lithium chloride solution (30 mL). The organic layer was dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue obtained was purified by chromatography (silica, methylene chloride to 39:1 methylene chloride/methanol) to afford methyl 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)-3-methylbenzoate (36 mg, 36%): ESI MS m/z 538 [M+H]+.

Provenance & Evidence