A Novel and Scalable Synthesis of Anlotinib Dihydrochloride via Titanium-Catalyzed Kulinkovich–Szymoniak Cyclopropanation

Synthesis 2026

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Authors: Phaneendra Gutala, Venkata Krishna Rao Badarla, Lekkala Amarnath Reddy, Sekhar Munaswamy Nariyam, Naveen Reddy Guntaka, Achugatla Gousia, Sachin Shahaji Bhosale
DOI: 10.1055/a-2816-6732
Cited by: 1
References: 16

Abstract

Abstract A novel, scalable, and column chromatography-free synthesis of Anlotinib dihydrochloride is described in this report. Synthesis of Anlotinib dihydrochloride is accomplished employing Kulinkovich–Szymoniak cyclopropanation reaction as the pivotal reaction for the first time for the installation of the key cyclopropylamine moiety in Anlotinib dihydrochloride. The aforesaid pivotal reaction circumvents the usage of an expensive key starting material (16) and potentially unsafe reagents such as azides, which are particularly not amenable for producing Anlotinib dihydrochloride on a commercial scale. The reported route avoids palladium in one of the key steps of the synthesis.

Fields of Study & Subjects

Click Chemistry and Applications Cyclopropane Reaction Mechanisms Chemical Reactions and Isotopes

Publication details

Journal / source
Synthesis
Publisher
Georg Thieme Verlag KG
Volume
58
Issue
10
Pages
1185–1190
Publication date
18 February 2026
Language
EN