Organic Chemistry

A revised synthesis of 6-alkoxy-2-aminopurines with late-stage convergence allowing for increased molecular complexity



6-alkoxy-2-aminopurine derivatives are potent inhibitors of Cyclin Dependent Kinases (CDKs), with some selectivity towards CDK2 and thus have potential as cancer therapeutics. Development of these inhibitors for targeting CDK2-cyclin A/E complexes has previously involved a thorough investigation of structure activity relationships of the C 2 amine moiety. However, the established synthesis of these compounds, which uses the alcohol reagent as solvent, limits the complexity of the O 6 functionality which is required for more selective targeting. Herein we report an improved and refocused synthesis of a model CDK2 inhibitor (NU6247), affording convenient access to inhibitors with O 6 substituents whose parent alcohol is not amenable for use as solvent. This revised synthesis allows for a meaningful exploration of the O 6 position in this class of CDK2 inhibitors.


Thumbnail image of CKI paper draft_V12.pdf

Supplementary material

Thumbnail image of CKI paper SI V7.pdf
Supporting information
Includes additional experimental data and NMR figures.