An efficient microwave assisted synthesis of N′-aryl/(alkyl)-substituted N-(4-hydroxy-6-phenylpyrimidin-2-yl)guanidines: Scope and limitations

• Published in: Tetrahedron letters 2017-06, Vol.58 (24), p.2318-2321
• Main Authors: Machicao, Paulo A., Burt, Scott R., Christensen, Ryan K., Lohner, Nathan B., Singleton, J.D., Peterson, Matt A.
• Format: Article
• Language: English
• Subjects: Compound libraries; Microwave assisted synthesis; N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]guanidine
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2017.03.063

[Display omitted] •An efficient method for preparing the title compounds is presented.•The reaction requires only 10min at 110–120°C under microwave conditions.•Products were obtained in excellent yields (65–84%).•Products were obtained in analytically pure form.•Total preparation time was approx. 1h (including isolation). Treatment of N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]cyanamide with 1° alkyl or arylamines in isopropyl alcohol for only 10min at 110–120°C under microwave conditions gave the corresponding N′-alkyl(aryl)guanidine derivatives in excellent yields (65–84%). Isolated yields were greatest when >1.0equiv. of amines were employed, but excellent results were also obtained when aryl and alkylamines were reacted with a more atom-economical loading (1.0equiv.; 70% and 72% ave. yields, respectively). Arylamines with either highly electron withdrawing substituents (e.g. CO2H) or pi-deficient heterocycles (e.g. variously substituted aminopyridines) did not work well under these conditions, and reaction with ureas and/or amino acids did not give detectable products. Work-up was exceedingly simple, and involved simple collection and washing of product on a sintered glass funnel. Products were obtained in analytically pure form and required approximately 1h to prepare, start to finish.