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Titanium(IV) isopropoxide mediated synthesis of pyrimidin-4-ones
Joshi M Ramanjulu1, Michael P Demartino, Yunfeng Lan
1Department of Medicinal Chemistry, Immuno-Inflamation CEDD, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA. joshi.m.ramanjulu@gsk.com
Abstract:
A novel, one-step method for the synthesis of tri- and tetrasubstituted pyrimidin-4-ones is reported. This method involves a titanium(IV)-mediated cyclization involving two sequential condensations of primary and beta-ketoamides. The reaction is operationally facile, readily scalable, and offers rapid entry into differentially substituted pyrimidin-4-one scaffolds. The high functional group compatibility allows for substantial diversification in the products generated from this transformation.
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