4-Methylmorpholine → 2-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide

Participants

Reaction Steps

4-Dimethylaminopyridine (DMAP), N-methylmorpholine and 3-fluoroaniline (in a large excess) were added to a suspension of (3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid.hydrochloride in N,N-dimethylacetamide (DMA) and the resulting slurry was stirred at or below room temperature. A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI.HCl) previously dissolved in water was then added in a controlled manner over a period of 8 hour so as to maintain the reaction at ambient temperature. The mixture was seeded with a small amount of product and left to stir for several hours. Anti-solvent acetonitrile followed by water were also added to precipitate more product. The material was isolated by filtration and the cake washed with a mixture of N,N-dimethylacetamide:water:acetonitrile, warm acetonitrile and then dried (in vacuo or under a stream of nitrogen) to yield 2-(3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide.

Provenance & Evidence