Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt.

Tobias Lucas,Till Opatz,Jule-Philipp Dietz

doi:10.3762/bjoc.16.41

Abstract

A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. The synthesis of fluorinated aminopyrazoles from the same fluorinated precursor could be demonstrated but proceeded with lower efficiency.

Highlights

Due to its extremely widespread application in virtually all areas of synthetic organic chemistry, fluorine is considered a “magic” element
Fluorinated pyrimidines, pyrimidine analogues and pyrazoles [20,21] play a prominent role in several clinically important pharmaceuticals [22,23,24,25]. These compounds act against HIV or HIV-related diseases [26], such as opportunistic fungal infections, and represent nucleoside analogues which can either act as antimetabolites or as nucleoside reverse transcriptase inhibitors (NRTIs)
Starting from formamidine hydrochloride, compound 10a was synthesized in 85% yield

Summary

Introduction

Due to its extremely widespread application in virtually all areas of synthetic organic chemistry, fluorine is considered a “magic” element. A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described potassium 2-cyano-2-fluoroethenolate was developed. A broad substrate scope was tested and mostly excellent yields were obtained. We present the synthesis of fluorinated pyrimidines and pyrazoles from the same precursor.

Results

Conclusion