Expedient Approach to the Synthesis of Betrixaban

Abstract

A new scalable route to synthesize the factor Xa (FXa) inhibitor betrixaban is disclosed. The product is obtained in a seven-step reaction sequence (in five stages using two one-pot reactions) starting from easily accessible 4-(N,N-dimethylcarbamimidoyl)benzoate. Effective isolation of intermediates, use of cost-effective amide formation and 2-methyltetrahydrofuran as an effective reaction solvent as well as for extraction in three of the stages, are key features. The strategy provides the desired product in 38% overall yield with high purity (>98%).

Keywords

• betrixaban
• factor xa (fxa) inhibitor
• anticoagulant
• one-pot reaction
• amidation