4-(4-Methylpiperazin-1-yl)aniline → HCID 57489643, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2,6-dichloro-5-fluoronicotinamide (1 g, 4.78 mmol) and 4-(4-methylpiperazin-1-yl)aniline (1.007 g, 5.26 mmol) in THF (30 mL) was added lithium bis(trimethylsilyl)amide (16.75 mL, 16.75 mmol) portionwise at −78° C. The mixture was stirred at −78° C. for 20 min and then removed from the dry ice bath. Next, the mixture was stirred at rt for 30 min. Two isomeric products were formed. The reaction mixture was quenched with water, extracted with ethyl acetate twice, washed the combined organic with water, and concentrated. The dark brown residue was triturated with methylene chloride, to give 570 mg of 2-chloro-5-fluoro-6-(4-(4-methylpiperazin-1-yl)phenylamino)nicotinamide as light brown solid. The mother liquor was concentrated and triturated again with methylene chloride to give 540 mg of 6-chloro-5-fluoro-2-(4-(4-methylpiperazin-1-yl)phenylamino)nicotinamide as brown solid. The mother liquor was purified twice by mPLC (ISCO, 7% ammonia/methanol/methylene chloride, 40 g+12 g stacked columns) to give an additional 490 mg of 6-chloro-5-fluoro-2-(4-(4-methylpiperazin-1-yl)phenylamino)nicotinamide as brown solid.

Provenance & Evidence