Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• aminopiperidine derivative bearing a spirocyclic ring on the piperidine moiety. Preparation of the aminopiperidine intermediate was carried out by constructing the cyclopropyl ring prior to assembling the piperidine ring. Keywords: Alogliptin; cyclopropyl ring; DPP-4; piperidine; Introduction Inhibition of

• derivative 9a. Preparation of 9a can be carried out following two strategies e.g. construction of cyclopropyl ring on piperidine moiety (Strategy 1) or vice versa (Strategy 2). While the use of first strategy for the preparation of 9a has been reported in the literature [11], application of other strategy is

• functionalized cyclopropyl ring (step i, Scheme 1) via a conventional C–C bond forming reaction. The reaction proceeded well to afford the functionalized cyclopropane derivative 1 as a result of the formation of two C–C bonds in a single step. Selective reduction of the cyano group of the resulting cyanoester 1