反应详情

A mixture of 2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride (5.92 g, 16.2 mmol) and Gold's reagent (3.5 g, 21.4 mmol) in dioxane (50 ml) was heated at reflux for 5 hours. Acetic acid (0.7 ml) and sodium acetate (1.33 g) were added to the reaction mixture which was heated at reflux for a further 5 hours. The mixture was allowed to cool and the volatiles were removed by evaporation. The residue was dissolved in water, adjusted to pH8 with 2M aqueous sodium hydroxide solution and purified on a Diaion (trademark of Mitsubishi) HP20SS resin column eluting with methanol (gradient 0-50%) in water. The fractions containing product were concentrated by evaporation and then freeze dried to give 4-hydroxy-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (4.55 g, 83%).

1. temperaturewas heated
2. temperatureat reflux for 5 hours
3. temperaturewas heated
4. temperatureat reflux for a further 5 hours
5. temperatureto cool
6. customthe volatiles were removed by evaporation
7. dissolutionThe residue was dissolved in water
8. custompurified on a Diaion (trademark of Mitsubishi) HP20SS resin column
9. washeluting with methanol (gradient 0-50%) in water
10. additionThe fractions containing product
11. concentrationwere concentrated by evaporation
12. customfreeze dried