(‐)‐Finerenone is a nonsteroidal mineralocorticoid receptor antagonist currently in phase III clinical trials for the treatment of chronic kidney disease in type 2 diabetes. It contains an unusual dihydronaphthyridine core. Herein, we report a 6‐step synthesis of (‑)‐Finerenone which features an enantioselective partial transfer hydrogenation of a naphthyridine using a chiral phosphoric acid catalyst with a Hantzsch ester. The process is complicated by the fact that the naphthyridine exists as a mixture of two atropisomers which react at different rates and different selectivities. The intrinsic kinetic resolution was converted into a kinetic dynamic resolution at elevated temperature which enabled us to obtain (‐)‐Finerenone in both high yield and high enantioselectivity. DFT calculations have revealed the origin of selectivity.
- enantioselective synthesis
- partial transfer hydrogenation
- pharmaceutical molecule
- MR antagonists