Download PDF
Synfacts 2018; 14(10): 1003
DOI: 10.1055/s-0037-1610905
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of AZD1656

Contributor(s):
Philip Kocienski
Hopes P. Langer T. Milard K. Steven A. * Cyton Biosciences Ltd., Bristol and AstraZeneca, Macclesfield, UK
Decoration of an α-Resorcylate Nucleus as Part of the Manufacture of a Glucokinase Activator.

Org. Process Res. Dev. 2018;
22: 996-1006
CrossrefSearch in Google Scholar
Further Information

Publication History

Publication Date:
17 September 2018 (online)

 
 PDF Download Permissions and Reprints

Key words

AZD1656 - glucokinase activator - Mitsunobu reaction - pyrazine ring formation - SNAr reaction

Significance

AZD1656 is a glucokinase activator that is of interest for the treatment of type 2 diabetes. The large-scale synthesis depicted involved the monobenzoylation of methyl α-resorcylate (A), a slurry-to-slurry reaction that relied on the insolubility of the monobenzoyl ester product F in the reaction medium and careful pH control.


#

Comment

Recrystallization of the API from MIBK gave the desired polymorph VI (mp not reported). This route provided 506 kg of AZD1565. A large-scale synthesis of water-soluble pyrazine I (three steps, 68% overall yield) has been described recently: Org. Process Res. Dev. 2018, 22, 77.


#
#


   Permissions and Reprints