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Synthesis
DOI: 10.1055/a-2816-6732
Paper

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

Authors

  • Phaneendra Gutala

    1   API R&D, Dr Reddy's Laboratories Ltd, Hyderabad, India (Ringgold ID: RIN28574)

  • Venkata Krishna Rao Badarla

    2   R&D, Dr Reddy's Laboratories Ltd, Hyderabad, India (Ringgold ID: RIN28574)

  • Lekkala Amarnath Reddy

    1   API R&D, Dr Reddy's Laboratories Ltd, Hyderabad, India (Ringgold ID: RIN28574)

  • Sekhar Munaswamy Nariyam

    1   API R&D, Dr Reddy's Laboratories Ltd, Hyderabad, India (Ringgold ID: RIN28574)

  • Naveen Reddy Guntaka

    1   API R&D, Dr Reddy's Laboratories Ltd, Hyderabad, India (Ringgold ID: RIN28574)

  • Achugatla Gousia

    3   API R&D, Dr Reddy's, Hyderabad, India (Ringgold ID: RIN28574)

  • Sachin Shahaji Bhosale

    1   API R&D, Dr Reddy's Laboratories Ltd, Hyderabad, India (Ringgold ID: RIN28574)
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A Novel and scalable 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 key cyclopropylamine moiety in Anlotinib dihydrochloride. The aforesaid pivotal reaction circumvents the usage of an expensive key starting material (21) 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.



Publication History

Received: 23 December 2025

Accepted after revision: 18 February 2026

Accepted Manuscript online:
18 February 2026

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