反应详情

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.

1. additionwas then added in a controlled manner over a period of 8 hour so as
2. temperatureto maintain
3. customthe reaction at ambient temperature
4. waitleft
5. stirringto stir for several hours
6. additionwere also added
7. customto precipitate more product
8. customThe material was isolated by filtration
9. washthe cake washed with a mixture of N,N-dimethylacetamide
10. temperaturewater:acetonitrile, warm acetonitrile
11. customdried (in vacuo