Pyrimidines Annulated Pyridine and Pyrimidine at Face d (2017–2025): A Comprehensive Survey of Synthetic Methodologies (Part 1)

ABSTRACT Pyrimidine is a fundamental heterocyclic scaffold with broad significance in chemical biology and pharmaceutical research. Although numerous reviews have focused on the biological activities of pyrimidine derivatives, comprehensive analyses dedicated specifically to pyrimidines fused at the face d position remain limited. In this context, face d‐annulation refers to the fusion of additional rings onto the C4–C5 edge of the pyrimidine core, generating structurally diverse condensed systems. This review provides a comprehensive literature survey covering the period from 2017 to 2025 and focuses exclusively on the synthetic development of pyrimidine frameworks annulated at face d. This review systematically organizes reported synthetic methodologies, discusses substrate scope and reaction conditions, and presents proposed mechanistic pathways where available. Particular emphasis is placed on pyridopyrimidines, pyrimidopyrimidines, and related fused heterocyclic systems constructed through diverse strategies. Unlike previous general reviews on pyrimidine synthesis, this work specifically concentrates on face d‐fused pyrimidine systems, thereby providing a focused and structured reference for researchers interested in this distinct structural class. The analysis presented herein aims to support further synthetic innovation and broaden the applications of pyrimidine‐based fused scaffolds.