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Chemoselective amination of 5-bromo-2-chloro-3-fluoropyridine
Bryan W Stroup1, Paul V Szklennik, Cornelia J Forster
1Global Discovery Chemistry, Novartis Institutes for BioMedical Research Inc, Cambridge, MA 02139, USA.
Abstract:
The chemoselective functionalization of 5-bromo-2-chloro-3-fluoropyridine (1c) is described. Catalytic amination conditions (Pd2dba3, Xantphos, base) afford exclusively the bromide substitution product (2) for both secondary amines and primary anilines. A reversal in chemoselectivity is observed under neat conditions in the absence of palladium catalysis, with substitution at the 2-chloro position preferred to generate 3. Last, selective substitution of the 3-fluoro group is achieved under SNAr conditions to afford the dihalo adduct (4).
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