An efficient microwave assisted synthesis of N′-aryl/(alkyl)-substituted N-(4-hydroxy-6-phenylpyrimidin-2-yl)guanidines: Scope and limitations. Issue 24 (14th June 2017)

• Record Type: Journal Article
• Authors: Machicao, Paulo A.; Burt, Scott R.; Christensen, Ryan K.; Lohner, Nathan B.; Singleton, J.D.; Peterson, Matt A.
• Is Part Of: Tetrahedron letters. Volume 58:Issue 24(2017)
• Page Start: 2318
• Page End: 2321
• Publication Date: 2017-06-14
• Subjects: N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]guanidine -- Compound libraries -- Microwave assisted synthesis; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2017.03.063
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: An efficient method for preparing the title compounds is presented. The reaction requires only 10 min 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. 1 h (including isolation). Abstract: Treatment of N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]cyanamide with 1° alkyl or arylamines in isopropyl alcohol for only 10 min 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 >1.0 equiv. of amines were employed, but excellent results were also obtained when aryl and alkylamines were reacted with a more atom-economical loading (1.0 equiv.; 70% and 72% ave. yields, respectively). Arylamines with either highly electron withdrawing substituents (e.g. CO2 H) 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 1 h to prepare, start to finish.