A mild and regiospecific synthesis of 3-amino substituted triazolo-[4,3-c]-pyrimidines by cyclisation of 4-hydrazinopyrimidines with iminium chlorides and with N-aryl phosgenimines

Article abstract of DOI:10.1016/S0040-4020(01)90525-3

Phosgeniminium chloride (PI) 1a permits the regiospecific synthesis of 3-dimethylaminotriazolo-[4,3-ch-pyrimidine 8a from the corresponding 4-hydrazinopyrimidine 5 without Dimroth type isomerisation into its [1,5-c isomer. This synthesis has been extended to the cyclic phosgeniminium salts 1b-e and to the N-aryl phosgenimines (aryl isocyanide dichlorides) 18a,b. The triazolopyrimidine structure was confirmed by an X-ray diffraction analysis of derivative 8d. When the Vilsmeier salt 10, tetramethylurea dichloride 11 or dimethyl(2,2,2-trifluoro-1,1-dichloroethyl)amine 12 were used as the electrophilic reagents, 4-methylenehydraiinopyrimidines 13, 14 and 15 respectively were isolated. Thermolysis of 13 yielded with the same regiospecificity 3-unsubstituted triazolo-[4,3-c-pyrimidine 16. This compound could be rearranged to 17 in a separate step. Chlorination of hydrazidopyrimidine 20 in refluxing POCl₃ led to the isomerised triazolo-[1, 5-ch-pyrimidine 22, as ascertained by X-ray diffraction and ¹³C-nmr analysis.