反应详情

温度

95 °C

A mixture of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (218 mg, 0.68 mmol), (prepared as described for the starting material in Example 9), 5-hydroxy-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.75 mmol) and potassium carbonate (280 mg, 2.0 mmol) in DMF (4 ml) was stirred at 95° C. for 6 hours and allowed to cool to ambient temperature. The reaction mixture was treated with 1.0 N aqueous sodium hydroxide solution and allowed to stir at ambient temperature for a few minutes. The resulting precipitate was filtered off, washed with water and air dried to give a crude product which was purified by column chromatography, eluting with dichloromethane/methanol/880 ammonia (100/8/1). The relevant fractions were combined and evaporated ‘in vacuo’ to give a white solid. This was recolumned using dichloromethane/methanol (4/1) solvent to give a white solid which was triturated with acetone, filtered and dried to give 6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)-4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline (50 mg, 18%).

1. custom(prepared
2. temperatureto cool to ambient temperature
3. stirringto stir at ambient temperature for a few minutes
4. filtrationThe resulting precipitate was filtered off
5. washwashed with water and air
6. customdried
7. customto give a crude product which
8. customwas purified by column chromatography
9. washeluting with dichloromethane/methanol/880 ammonia (100/8/1)
10. customevaporated ‘in vacuo’
11. customto give a white solid
12. customto give a white solid which
13. customwas triturated with acetone
14. filtrationfiltered
15. customdried