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DOI: 10.1055/s-0041-1737097
Synthesis of AZD7624
Expedited Kilolab Development of AZD7624 Using Kulinkovich–de Meijere Cyclopropanation.
Org. Process Res. Dev. 2021;
25: 2351-2366
DOI: 10.1021/acs.oprd.1c00283.
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.
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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.
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Publikationsverlauf
Artikel online veröffentlicht:
17. November 2021
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