Relebactam (MK-7655) is a class A and class C beta-lactamase inhibitor potentially useful for the treatment, in combination with imipenem/cilastatin, of serious bacterial infections. This combination has recently completed two Phase 2 and one Phase 3 studies. The current manufacturing route to relebactam utilizes a non-commodity starting material and has poor atom economy due to usage of several protecting groups. These challenges prompted a search for a more efficient synthesis. Here we describe our progress on a new synthesis to the key diamine intermediate intercepting current manufacturing route. The synthesis starts from readily available Boc pyroglutamic acid and features an effective ring-expansion, a novel diastereoselective FeCl3/NaBH4 reduction of oxime and a selective amidation of a pipecolic acid derivative. The development of the new route is expected to have significant cost saving as well as addressing other synthetic challenges for the preparation of the diamine common intermediate.

Development of an efficient route to beta-lactamase inhibitor relebactam (MK-7655)

2019 Fall National Meeting

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