ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Novel method for the synthesis of lenvatinib using 4-nitrophenyl cyclopropylcarbamate and their pharmaceutical salts

Ravi Kumar Sadineni, Rajesh Kumar Rapolu, V. V. N. K. V. Prasada Raju, N. Srinivasu, Sireesha Malladi, and Naveen Mulakayala

Granules India Limited, R&D Center, Hyderabad, India

E-mail: naveen071280@gmail.com

Received: 22 June 2020  Accepted: 20 October 2020

Abstract:

4-Nitrophenyl cyclopropylcarbamate was deployed as a novel synthon for the synthesis of anticancer drug lenvatinib. 4-Nitrophenyl cyclopropylcarbamate was prepared by the reaction of 4-nitrophenyl chloroformate and cyclopropyl amine in acetonitrile at room temperature. Furthermore, lenvatinib was synthesized by reacting 4-(4-amino-3-chlorophenoxy)-7-methoxyquinoline-6-carboxamide with 4-nitrophenyl cyclopropylcarbamate in good yields. Apart from the synthesis of lenvatinib, citrate, phosphate, malate and oxalate salts of lenvatinib were also reported in good yields.

Keywords: Synthesis; Process; Lenvatinib; Salts; Analysis

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01402-z

Chemical Papers 75 (4) 1475–1483 (2021)