Synthesis of Mono‐ and Bis(fluoroalkyl)pyrimidines from FARs, Fluorinated Acetoacetates, and Malononitrile Provides Easy Access to Novel High‐Value Pyrimidine Scaffolds

• Published in: Chemistry : a European journal Vol. 24; no. 6; pp. 1311 - 1316
• Main Authors: Schmitt, Etienne, Commare, Bruno, Panossian, Armen, Vors, Jean‐Pierre, Pazenok, Sergiy, Leroux, Frédéric R.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.01.2018; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Carboxylates; Carboxylic acids; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; cyclization; Fluorination; fluorine; heterocycles; Irradiation; Malononitrile; Organic chemistry; Physical Sciences; pyrimidine; Pyrimidines; Reagents; Scaffolds; Science & Technology; synthetic methods; PYRAZOLES; REAGENTS; heterocycles; LIGAND; cyclization; pyrimidine; synthetic methods; fluorine; ETHYL; LIFE
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201703982

A new strategy was developed using fluorinated acetoacetates, malononitrile, and fluoroalkyl amino reagents (FARs) to access unprecedented 4,6‐bis(fluoroalkyl)pyrimidine‐5‐carboxylates, their carboxylic acid analogues, and 4‐amino‐6‐(fluoroalkyl)pyrimidine‐5‐carbonitriles. An efficient cyclization step using suitable amidines was developed under microwave irradiation, providing the desired pyrimidines rapidly and efficiently. Standard saponification conditions were applied from carboxylate derivatives to access to the corresponding carboxylic acids. These new valuable building blocks, bearing either a single or two emergent fluorinated substituents, hold strong potential for medicinal and agrochemical research. Fluorinated building blocks: An efficient microwave‐assisted cyclization reaction was developed that provides rapid and efficient access to new fluoroalkyl pyrimidines from fluorinated acetoacetates, malononitrile, various amidines, and fluoroalkyl amino reagents (FARs).