Synthesis of AZD7624

Key words

AZD7624 - cyclopropanation - Buchwald–Hartwig reaction - de Meijere reaction - Kulinkovich reaction

Significance

The p38α mitogen-activated protein kinase is expressed and activated in several cell types associated with chronic obstructive pulmonary disease (COPD). AZD7624 inhibits p38a but its development was halted after phase 2a trials failed to show any benefit over placebo. The synthesis depicted delivered 5.3 kg of API.

Comment

A noteworthy feature of the synthesis is the implementation of the de Meijere modification of the Kulinkovich cyclopropanation that converts the benzonitrile G to the cyclopropylamine H in 37% yield on a 22.6 mol scale. On a laboratory scale the yield was 57%. For an alternative synthesis of AZD7624, see: WO 2017 162304 A1.

Publication History

Article published online:
17 November 2021