反应详情

Methoxyacetaldehyde (368 mg, 3.47 mol) (freshly distilled) followed by sodium triacetoxyborohydride (552 mg, 2.6 mol) were added to a solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (726 mg, 1.74 mmol), (prepared as described in Example 70), in a mixture of methylene chloride (15 ml) and methanol (15 ml). After stirring for 1.5 hours at ambient temperature, saturated sodium hydrogen carbonate was added. The volatiles were removed under vacuum and the residue was partitioned between methylene chloride and water. The organic layer, was separated, washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (80/20). After removal of the solvent, the residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 60° C. to give 6-methoxy-7-(1-(2-methoxyethyl)piperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline (392 mg, 47%).

1. customThe volatiles were removed under vacuum
2. customthe residue was partitioned between methylene chloride and water
3. customThe organic layer, was separated
4. washwashed with water, brine
5. dry with materialdried (MgSO4)
6. customthe volatiles were removed by evaporation
7. customThe residue was purified by column chromatography
8. washeluting with methylene chloride/methanol (80/20)
9. customAfter removal of the solvent
10. customthe residue was triturated with ether
11. filtrationcollected by filtration
12. washwashed with ether
13. customdried under vacuum at 60° C.