Isay condensation

Since the structures of the Gabriel-Isay condensation products of 5,6-diaminopyrimidines with unsymmetrical 1,2-dicarbonyl or a-substituted monocarbonyl compounds are always ambiguous, the synthesis of 6- and 7-substituted pteridines by an unambiguous approach was and still is a necessity and an important challenge. 

Aldol Condensation Claisen Condensation Claisen-Schmidt Condensation Cyclocondensation Friedlander Condensation Isay Condensation Knoevenagel Condensation Pechmann Reaction Ugi Condensation... 

Purine (6) itself is a colorless crystalline weak base which was first prepared by Fischer " the first synthesis using the Traubc condensation was reported by Isay. The Traube protocol is probably the best method to prepare purine, using pyrimidine-4,5-diamine as precursor and formic acid in an atmosphere of carbon dioxide or diethoxymethyl acetate as cyclizing reagents. 

The synthesis of the pteridine ring system has been approached by two obvious routes one is the fusion of the pyrazine ring onto a pre-formed 4,5-diamino-pyrimidine, and the second, the elaboration of the pyrimidine ring on a pre-formed pyrazine. The first of these, the Isay synthesis, suffers from the disadvantage that condensation of the heterocyclic 1,2-diamine with an unsymmetrical 1,2-dicarbonyl compound... 

In 2002 Isay-type condensations for synthesis of 6-substituted pterins, including pterin sugar derivatives and 2-substituted quinoxalines, were developed under microwave irradiation conditions [103]. Interestingly, the isomer-free 6-substituted pterins desired were obtained in moderate to good yields whereas mixtures of both 6- and 7-isomers (major) are usually formed when conventional Isay type condensations are used. 

A regioselective synthesis of 6-substituted pterins 729, 730, and 731 was achieved using an MW-assisted direct Isay-type condensation of triamine 728 with methyl-glyoxal or aldohexoses to give under MWI, without addition of sodium bisulfate or hydrazine hydrate, 729 in 70% yield within 62 s and the sugar derivatives 730 and 731 in 40% and 38% yields, respectively, within 270 s (Scheme 141) (02TL8371). 

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