Scalable routes to both the core and tail fragments of the NS4B Inhibitor GSK2585337A have been developed. Two distinct routes to the pyrazolopyridine core have been demonstrated in fixed equipment, both relying on starting materials that incorporate the problematic N-N bond. For the tail fragment, the new synthesis utilizes a diasteroselective sulfur ylide cyclopropanation-reduction sequence to circumvent the problematic Simmons-Smith cyclopropanation and Curtius rearrangement steps associated with the original route. The key to diastereocontrol in these reactions is the choice of protecting group on the amine. 

Circumventing highly energetic reactions: Development of a scalable synthesis of the hepatitis c NS4B inhibitor GSK2585337A

248th National Meeting (2014)

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