Ionic Liquid Phase Organic Synthesis (IoLiPOS) Methodology Applied to the Preparation of New 3,4-Dihydropyrimidine-2(1H)-ones Bearing Bioisostere Group in N-3 Position
[en] The ionic liquid phase organic synthesis (IoLiPOS) methodology has been used for the preparation of new 3,4-dihydropyrimidine-2(1H)-ones (DHPMs) bearing bioisostere group in N-3 position. For the 3,4-DHPMs substituted with various thiazole rings, the strategy involved a three-component Biginelli condensation in the second step with good yields (93-96%) from ILP bound acetoacetate, aromatic aldehyde (93-97% yield), and N-methyl urea followed by N-3 alkylation with chloroacetonitrile on the ILP bound 3,4-DHPM. Quantitative thionation of the nitrile group grafted on the ILP bound 3,4-DHPM was realized in MeOH with a 40-48% solution of ammonium sulfide and subsequent addition of a-bromoketone produced the thiazole ring appended on the 3,4-DHPM core. After cleavage by transesterification, the target compounds were obtained in good overall yields (47-50%). The efficiency of the IoLiPOS methodology was also demonstrated by the preparation of new 3,4-DHPMs with a tetrazole ring in N-3 position in 5 steps (53-61% overall yield) via the ILP bound 3-cyanomethyl 3,4-DHPM as key intermediate.
Disciplines :
Chemistry
Author, co-author :
Legeay, J.-C.
Vanden Eynde, Jean-Jacques ; Université de Mons > Faculté des Sciences > Synthèse et spectrométrie de masse organiques
Bazureau, J.P.
Language :
English
Title :
Ionic Liquid Phase Organic Synthesis (IoLiPOS) Methodology Applied to the Preparation of New 3,4-Dihydropyrimidine-2(1H)-ones Bearing Bioisostere Group in N-3 Position
Publication date :
26 May 2008
Journal title :
Tetrahedron
ISSN :
0040-4020
Publisher :
Elsevier, United Kingdom
Volume :
64
Issue :
22
Pages :
5328 - 5335
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
S836 - Synthèse et spectrométrie de masse organiques
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