In the manufacturing route towards AMG 853, one of the key transformations comprised a palladium-catalyzed sulfonamide cross-coupling with an aryl bromide to form an advanced intermediate.  Due to the catalyst/ligand costs, and extensive metal removal expenditure in the palladium process, an attractive and competitive copper-catalyzed process was developed.  A nitrile-based additive was found to be necessary to increase catalyst productivity affording a mild process which tolerated multiple functionalities.  These conditions were generalized for a broad set of aryl bromides and sulfonamides including the first reported room-temperature copper-catalyzed sulfonamide coupling. 

Replacing palladium: Development of a general copper-catalyzed sulfonamide coupling under mild conditions

246th National Meeting (2013)

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