Chemistry of Polyhalogenated Nitrobutadienes, 6: A New Ring-Closure Approach to Perfunctionalized 5-Nitropyrimidines

Abstract

The recently reported capability of pentachloro-2-nitrobutadiene and some closely related derivatives to allow the synthesis of highly substituted acyclic as well as five-membered (hetero)cyclic compounds is herein extended to pyrimidines with an exceptional substitution pattern. Our novel approach starts from a 1,1-diamino-3,4,4-trichloro-2-nitrobuta-1,3-diene and an appropriate amidine. Some of the resulting perfunctionalized pyrimidines were subjected to further transformations to give promising candidates with respect to biological, especially pharmacological, activity.

Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds

“…In the course of the studies concerning polyhalogenated nitrobutadienes, a new ring closure approach to perfunctionalized 5-nitropyrimidines was also developed [33]. Using this protocol starting from 25c-f, four new nitropyrimidines 27c-f were obtained.…”

“…Even under optimum conditions, yields of the products 27c-f remained moderate, reaching 49-65%. The assumed mechanism for the formation of pyrimidines 27 has been presented in the literature [33]. 5-Nitro-substituted pyrimidines are interesting precursors for the synthesis of a wide range of poly-substituted pyrimidines and other heterocyclic systems with potential biological activity [34].…”

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

“…The latter, on one hand was converted by treatment with acetamidine hydrochloride in THF to the pyrimidine 26 (yield 58%), which apparently proceeds by transamination and subsequent intramolecular S N Vin reaction. The structure of an analogous derivative of this heterocycle was previously confirmed by X-ray crystallography [5]. On the other hand, nitrodiene 25 was treated with arylhydrazines to give the persubstituted aminonitropyrazoles 27 – 28 in 75–90% yield (Scheme 6).…”

“…However, the individual parts of these multistep reactions, namely the conversion of the 1-amino-2,2-dichlorovinyl group to a dichloromethyl ketone and, in addition, the reductive bisdechlorination of a dichloromethyl group were recently published by our group [5,43]. …”

Chemistry of polyhalogenated nitrobutadienes, 19: synthesis of new types of compounds modulating the biological activity of type I Interferons (IFN-I).

“…13 C NMR (100 MHz, CDCl3): δ = 170.8 and 169.9 (C=O and SCS), 138.8 (NCq), 130.4 (CNO2), 114.3 (CCl2), 75.8 (CH), 69.0 (OCH2), 49.7, 48.9, 45.6 and 42.1 (4 NCH2), 40.1 (SCH2), 37.6 (SCH2), 28.3 (CH2), 25.6 (CH2). MS (EI, 70 eV): m/z (%) = 439 (22) [M + ], 403 (10) [M -HCl] + , 376 (20), 311 (38), 210 (100) [M -NO2 -N(CH2)4N-CO-C4H7O] + , 183 (5) [N(CH2)4N-CO-C4H7O] + . HRMS-EI: calcd.…”