Review on Synthetic Approaches toward Rivaroxaban (Xarelto), an Anticoagulant Drug

Venous thromboembolism including deep vein thrombosis and pulmonary embolism is an abundant and dangerous disease with significant relapse probability and mortality. In pursuit of an effective treatment, Bayer created Rivaroxaban, nowadays known under the brand name Xarelto, that was approved by the FDA in 2011. By 2022, the number of main indications for the drug has been increased 10-fold as well as the drug’s prevalence in the field of thrombosis treatment. It is therefore apparent that with growing prescriptions new synthetic pathways are highly desirable, especially those utilizing inexpensive and safe reagents in environmentally benign protocols. The present work reviews the literature concerning Rivaroxaban preparation with an emphasis on the applicability of synthetic pathways on a large scale. Within the synthetic sequences, common intermediates are discussed in detail and relevant comparisons are made. Our main purpose is to provide an overview of the subject in its current state, paying attention to advances made and suggesting possible directions for further development.