反应详情

温度

90 °C

2-(3-{[7-(3-Chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide and 2-(ethylamino)ethanol (12 molar equivalents) were added to N,N-dimethylacetamide under an inert atmosphere (such as provided by nitrogen) and the mixture heated to 90° C. with stirring. After 12 hours, water was added in a controlled manner and the batch seeded with product whilst hot. The mixture was cooled to 20° C. in a carefully controlled manner to crystallise the product in the required form. The product was then filtered and washed with a mixture of water/N,N-dimethylacetamide and acetonitrile. Following this, the cake was slurried for a period with warm acetonitrile (40° C.), filtered, washed with more acetonitrile and then dried (in vacuo or under a stream of nitrogen) to afford the anhydrous 2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide as an off-white solid in a yield of ˜90%.

1. temperatureThe mixture was cooled to 20° C. in a carefully controlled manner
2. customto crystallise the product in the required form
3. filtrationThe product was then filtered
4. washwashed with a mixture of water/N,N-dimethylacetamide and acetonitrile
5. waitwas slurried for a period with warm acetonitrile (40° C.)
6. filtrationfiltered
7. washwashed with more acetonitrile
8. customdried (in vacuo