Synfacts 2008(4): 0433-0433  
DOI: 10.1055/s-2008-1042774
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart · New York

Solid-Phase Synthesis of 1,2,4-Triazolo[1,5-a]pyrimidines

Contributor(s): Yasuhiro Uozumi, Yohei Oe
C. L. Cavallaro*, L. S. Harikrishnan, F. Chi, D. Dodd, A. Purandare
Bristol-Myers Squibb R & D, Princeton, USA
Further Information

Publication History

Publication Date:
19 March 2008 (online)

Significance

The polymer-supported synthesis of 2,7-diaminosubstituted [1,2,4]triazolo[1,5-a]pyrimidines 8 was described. Thus, the reductive amination of the polystyrene-supported aldehyde 1 with amines gave polymer-bound amines 2. Treatment of 2 with diphenoxycyanoimidate afforded the corresponding phenyl isoureas 3. The isoureas 3 reacted with hydrazine to form 1,2,4-triazoles 4. The reaction of 4 with ethyl (ethoxymethylene)cyanoacetate, followed by the treatment with KHMDS and elevating the temperature furnished triazopyrimidinones 5. After the formation of chlorotriazolopyrimidines 6 by the treatment of 5 with POCl3, the substitution reaction of 6 with amines yielded polymer-bound 2,7-diaminosubstituted 1,2,4-triazolo[1,5-a]pyrimi­dines 7. The polymer support was cleaved by TFA to provide 8 in 7-25% total yield.