One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1H-Pyrazol-5-yl-N,N-dimethylformamidines or 5-Amino-1H-pyrazole-4-carbaldehydes with Cyanamide

Abstract

A convenient and efficient one-pot acidpromoted synthesis of 6-aminopyrazolo [3,4-d]pyrimidine has been developed by treatment of 1H-pyrazol-5-yl-N,N-dimethylformamidines or 5-amino-1H-pyrazole-4-carbaldehydes with cyanamide (NH 2 CN) in an acid-mediated solution. This synthetic route involves four steps of deprotection, imination, the key acid-promoted heterocyclization, and aromatization. On the basis of optimized studies, methanesulfonylchloride is considered to be the best solvent. Furthermore, the microwave-assisted synthetic technique was also carried out to improve the major product 6-aminopyrazolo [3,4d]pyrimidines in this method. Moreover, our proposed mechanism was confirmed in this study, which demonstrates that N-[(5amino-1,3-diaryl-1H-pyrazol-4-yl)methylene]cyanamide is the intermediate.

Recent developments on microwave-assisted organic synthesis of nitrogen- and oxygen-containing preferred heterocyclic scaffolds

“…An acid-promoted one-pot development of 6-amino-pyrazolopyrimidines was reported by Wong and co-workers. 92 The reaction was carried out with 1 H -pyrazol-5-yl- N , N -dimethylformamidines or 5-amino-1 H -pyrazole-4-carbaldehydes 76a–o and cyanamide (NH 2 CN) in an acid-mediated solution applying microwave conditions at 55 °C to afford good isolated yields (63–86%) of desired compounds 77a–o ( Scheme 27 ). The overall reaction involves deprotection, imination, acid promoted heterocyclization and aromatization.…”