Spirocyclic oxetanes have emerged as useful building blocks within medicinal chemistry. For example, small saturated heterocycles with an appended spirocyclic oxetane present a conformationally-constrained, compact three-dimensional architecture, with an attractive physicochemical profile. Incorporation of a spiro-oxetane may result in an increase in aqueous solubility, while simultaneously reducing unwanted off-target activities (e.g. hERG), and improving metabolic stability. As part of our on-going research in to kinase inhibitors, we sought to prepare a tricyclic building block containing a spirocyclic oxetane substructure. In this paper, we show that our efforts to prepare the spirocyclic oxetane 1, from a suitably functionalized acyclic precursor 2, did not yield the expected spiro-oxetane product, but instead resulted in the formation of 9-nitro-5H-spiro[benzo[b]tetrazolo[1,5-d][1,4]oxazepine 3 via an unusual ring expansion process. We also show that compound 3 can itself serve as a useful building block, via reaction of the epoxide (oxirane) ring.

Unusual ring-expansion reaction to prepare 9-Nitro-5H-spiro[benzotetrazolo[1,5-d]oxazepine-4,2’-oxirane]

253rd National Meeting (2017)

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