A new and efficient protocol for the synthesis of the key intermediate of Palbociclib. Issue 1 (January 2019)

• Record Type: Journal Article
• Authors: Li, Shuting; Yang, Wanfeng; Ji, Min; Cai, Jin; Chen, Junqing
• Is Part Of: Journal of chemical research. Volume 43:Issue 1/2(2019)
• Page Start: 14
• Page End: 19
• Publication Date: 2019-01
• Subjects: cyclin-dependent kinase inhibitor -- Palbociclib -- Palbociclib intermediate -- synthesis; Chemistry -- Research -- Periodicals; Chemistry -- Periodicals; 540.5
• DOI: 10.1177/1747519819831858
• Languages: English
• ISSNs: 1747-5198

Abstract

A new and efficient synthesis of 6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)-pyrido[2, 3-d]pyrimidin-7(8H)-one, a key intermediate of Palbociclib, starting from thiouracil was described. This protocol involved methylation, nucleophilic substitution, bromination, nucleophilic substitution, Heck reaction, ring closure, oxidation, and bromination to afford a key intermediate of Palbociclib with approximately 35% overall yield. The advantages of this developed synthetic strategy included improved overall yield, inexpensive starting materials, and readily controllable and cleaner reaction conditions.