1,3-Dibromo-1,1-difluoro-2-propanone as a Useful Synthon for a Chemoselective Preparation of 4-Bromodifluoromethyl Thiazoles

Marco Colella; Pantaleo Musci; Claudia Carlucci; Samuele Lillini; Mara Tomassetti; Andrea Aramini; Leonardo Degennaro; Renzo Luisi

doi:10.1021/acsomega.8b02273

1,3-Dibromo-1,1-difluoro-2-propanone as a Useful Synthon for a Chemoselective Preparation of 4-Bromodifluoromethyl Thiazoles

ACS Omega. 2018 Nov 5;3(11):14841-14848. doi: 10.1021/acsomega.8b02273. eCollection 2018 Nov 30.

Authors

Marco Colella¹, Pantaleo Musci¹, Claudia Carlucci¹, Samuele Lillini², Mara Tomassetti², Andrea Aramini^{3

2}, Leonardo Degennaro¹, Renzo Luisi¹

Affiliations

¹ Department of Pharmacy-Drug Sciences, University of Bari "A. Moro" Via E. Orabona 4, Bari 70125, Italy.
² Department of Discovery, Dompé Farmaceutici S.p.A., Via Pietro Castellino, Napoli 80131, Italy.
³ Department of Discovery, Dompé Farmaceutici S.p.A., Via Campo di Pile, L'Aquila 67100, Italy.

Abstract

We report herein a synthetic protocol for the preparation of 1,3-dibromo-1,1-difluoro-2-propanone, a new synthon used for the first time in a reaction with aromatic amines and sodium thiocyanate, leading to thiazoles which are useful candidates in drug discovery programs. The new synthon allows to introduce a bromodifluoromethyl group at the C4 of the thiazole, and it is amenable of further transformation such as the Br/F exchange useful in radiopharmaceutics. Application of the strategy to the preparation of a precursor of the biologically relevant DF2755Y is also reported.