Synthesis of cyclic guanidines: 2-arylamino-1,4,5,6-tetrahydropyrimidines

Abstract

Considering the biological and chemical relevance of guanidine containing derivatives, we have devised a novel and efficient two-step synthesis of 2-arylamino-1,4,5,6-tetrahydropyrimidines. We have found that the coupling of aryl bromides with 2-aminopyrimidine is a very effective method for the high yielding synthesis of 2-arylaminopyrimidines. Moreover, the employment of Pd-catalysed hydrogenation to selectively reduce the pyrimidine ring generates a very highyielding pathway to 2-arylamino-1,4,5,6-tetrahydropyrimidines of biological interest.

Synthesis of 3-amino-substituted benzothiadiazine oxides by a palladium-catalysed cascade reaction

“…First, amine 4a was applied in a Buchwald–Hartwig amination. 28 Under non-optimised and literature conditions, 29 amine 4a was treated with bromobenzene ( 5 ) using a combination of Pd 2 (dba) 3 and Xantphos as catalyst. As a result, heterocycle 3ah was isolated in 58% yield.…”

Reactivity of tetrazolo[1,5-a]pyrimidines in click chemistry and hydrogenation

“…Reducing aminopyrimidines is more commonly found in the literature, for example, Baskaran et al [16] reduced 2-aminopyrimidines using triethylsilane (TES) in trifluoroacetic acid (TFA). 2-Aminodihydro pyrimidine formation occurred at lower temperatures, and aminotetra hydropyrimidines were observed when the reaction was run in refluxing TFA for 24 h. In 2014, Shaw et al [17] reduced 2-arylaminopyrimidines using palladium on carbon (Pd/C) in MeOH, forming 2-arylamino-tetrahydro pyrimidines in excellent yields (71-98 %). Asymmetric hydrogenation of pyrimidines is an efficient method of synthesizing chiral dihydro-or tetrahydropyrimidines despite the asymmetric hydrogenation of pyrimidines being a novel theme in organic synthesis, and only recently have papers been published on this topic [18][19][20].…”