反应详情

Diethyl azodicarboxylate (0.09 g, 0.518 mmol) was added dropwise to a solution of 4-(7-azaindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (0.133 g, 0.432 mmol), triphenylphosphine (0.17 g, 0.647 mmol) and 3-(4-methylsulphonylpiperazin-1-yl)propan-1-ol (0.115 g, 0.519 mmol) in DMF (4 ml) and the mixture was stirred at ambient temperature for 1 hour. The volatiles were removed under vacuum and the residue was purified by column chromatography using increasingly polar mixtures of ethyl acetate and methylene chloride followed by methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The solid was then repurified by preparative LC/MS eluting with acetonitrile/water (containing 1% acetic acid). The fractions containing the expected product were combined and evaporated. The residue was dissolved in aqueous sodium hydrogen carbonate and methylene chloride. The organic phase was separated and dried over magnesium sulphate and evaporated. The residue was triturated under diethyl ether, filtered, washed with ether and dried under vacuum over P2O5 to give 4-(7-azaindol-5-yloxy)-7-methoxy-6-(3-(4-methylsulphonylpiperazin-1-yl)propoxy)quinazoline (0.09, 40%).

1. customThe volatiles were removed under vacuum
2. customthe residue was purified by column chromatography
3. temperatureusing increasingly polar mixtures of ethyl acetate and methylene chloride
4. additionThe fractions containing the expected product
5. customevaporated
6. customThe solid was then repurified by preparative LC/MS
7. washeluting with acetonitrile/water (containing 1% acetic acid)
8. additionThe fractions containing the expected product
9. customevaporated
10. dissolutionThe residue was dissolved in aqueous sodium hydrogen carbonate
11. customThe organic phase was separated
12. dry with materialdried over magnesium sulphate
13. customevaporated
14. customThe residue was triturated under diethyl ether
15. filtrationfiltered
16. washwashed with ether
17. dry with materialdried under vacuum over P2O5