New Strategies for the Synthesis of Pyrimidine Derivatives

Abstract

Recent advances in pyrimidine synthesis are described. Modification of conventional strategies involving N-C-N fragment condensation with 1,3-dicarbonyl derivatives remains a common theme in current literature. Other methods, including N-C fragment condensation strategies, provide reactive intermediates capable of intramolecular cyclization and formation of pyrimidine derivatives. These recently developed methodologies offer a valuable addendum to azaheterocycle synthesis.

One‐Pot, Atom and Step Economy (PASE) Assembly of Trifluoromethylated Pyrimidines from CF3‐Ynones

“…Many pyrimidine‐derived drugs are used mainly as anticancer, antiviral, anti‐HIV, antibacterial, and antifungal agents (Figure ) . A number of methods for their preparation have already been described . The most common approach to the non‐fluorinated pyrimidines involves the cyclocondensation reaction of 1,3‐dicarbonyl compounds or their equivalents with 1,3‐bis(nucleophile)s that contain the N–C–N moiety such as amidines, guanidines, ureas, and their derivatives.…”

Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination

“…[1] Accordingly, a reliable and efficient entry into such a class of compounds represents a highly important task. However, a brief survey of the literature reveals that direct approaches to the preparation of N-alkylated 2-pyridones are much less well explored, [2] likely because of the competing process between O and N alkylation given their ambivalent charac-ter. [3] In this regard, the rearrangement reactions starting from O-substituted pyridines have been developed to address this problem through O to N alkyl migration by sp 3 CÀO bond cleavage [4] or Claisen rearrangement.…”

Synthesis of Tri‐ or Tetrasubstituted Pyrimidine Derivatives through the [5+1] Annulation of Enamidines with either N,N‐Dimethylformamide Dialkyl Acetals or Orthoesters and Their Application in a Ring Transformation of Pyrimidines to Pyrido[2,3‐d]pyrimidin‐5‐one Derivatives

“…A variety of approaches for the synthesis of pyrimidine derivatives have been developed by a number of organic and pharmaceutical chemists. [1,[8][9][10][11] Most general synthetic routes to the pyrimidine framework utilize one of the following procedures (Scheme 2): i) [3+3] annulation between an N À C À N and a C À C À C fragment (known as the Pinner-type synthesis; [12] path a), [13,14] or between a C À C À N and a C À N À C fragment (path b); [15] ii) [4+2] annulation of a C À C À N À C fragment with a C À N fragment (path c), [16] a C À C À C À N fragment with a C À N fragment (path d), [17] or a C À NÀCÀN fragment with a CÀC fragment (path e); [18] and iii) [5+1] annulation of a NÀCÀCÀCÀN fragment with a C1 unit (path f), [19] or of a CÀNÀCÀCÀC fragment with an N1 unit (path g). [20] To our knowledge, the [5+1] annulation of a C À C À N À C À N fragment with a C1 unit has not yet been studied (path h).…”