反应详情

温度

100 °C

A solution of 1-(3-chloropropyl)pyrrolidine (230 mg, 0.96 mmol) was added to 44-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (295 mg, 0.92 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (130 mg, 0.94 mmol) in DMF (8 ml). The mixture was heated at 100° C. for 90 minutes and allowed to cool. The volatiles were removed by evaporation and the residues were partitioned between water and methylene chloride. The organic phase was separated and passed through phase separating paper, and the solvent was removed under reduced pressure. The residue was dissolved in acetone and hydrogen chloride in ether (2 ml of a 1M solution, 2 mmol) was added. The mixture was stirred at ambient temperature for 30 minutes and the resulting precipitate was collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)6-methoxy-7-(3-pyrrolidin-1-yl)propoxy)quinazoline hydrochloride hydrate (320 mg, 67%).

1. custom(prepared
2. temperatureto cool
3. customThe volatiles were removed by evaporation
4. customthe residues were partitioned between water and methylene chloride
5. customThe organic phase was separated
6. customseparating paper
7. customthe solvent was removed under reduced pressure
8. dissolutionThe residue was dissolved in acetone
9. additionhydrogen chloride in ether (2 ml of a 1M solution, 2 mmol) was added
10. filtrationthe resulting precipitate was collected by filtration
11. customdried