Regioselective Quinazoline C2 Modifications through the Azide–Tetrazole Tautomeric Equilibrium
Beilstein Journal of Organic Chemistry 2024
Dāgs Dāvis Līpiņš, Andris Jeminejs, Una Ušacka, Anatolijs Mišņovs, Māris Turks, Irina Novosjolova

2-Chloro-4-sulfonylquinazolines undergo functional group swap when treated with an azide nucleophile: 1) the azide replaces the sulfonyl group at the C4 position; 2) the intrinsic azide–tetrazole tautomeric equilibrium directs the nucleofugal sulfinate from the first step to replace chloride at the C2 position. This transformation is effective with quinazolines bearing electron-rich substituents. Therefore, the title transformations are demonstrated on the 6,7-dimethoxyquinazoline core, which is present in pharmaceutically active substances. The methodology application is showcased by transforming the obtained 4-azido-6,7-dimethoxy-2-sulfonylquinazolines into the α1-adrenoceptor blockers terazosin and prazosin by further C2-selective SNAr reaction and azide reduction.


Keywords
quinazolines, azide-tetrazole equilibrium, sulfonyl group dance
DOI
10.3762/bjoc.20.61
Hyperlink
https://www.beilstein-journals.org/bjoc/articles/20/61

Līpiņš, D., Jeminejs, A., Ušacka, U., Mišņovs, A., Turks, M., Novosjolova, I. Regioselective Quinazoline C2 Modifications through the Azide–Tetrazole Tautomeric Equilibrium. Beilstein Journal of Organic Chemistry, 2024, Vol. 20, pp.675-683. ISSN 1860-5397. Available from: doi:10.3762/bjoc.20.61

Publication language
English (en)
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