The Synthetic Routes of Idelalisib

Synthetic routes of Idelalisib: A Comprehensive Overview

Idelalisib is a phosphatidylinositol 3-kinase (PI3K) inhibitor used for the treatment of various types of cancer, including chronic lymphocytic leukemia (CLL) and follicular lymphoma.
The chemical structure of Idelalisib is complex, consisting of a tetrahydroquinoline moiety and a alkoxy carbonyl group, making it challenging to synthesize.
Several synthetic routes have been reported in the literature for the synthesis of Idelalisib, each with its own advantages and disadvantages.
In this article, we will provide a comprehensive overview of the existing synthetic routes for Idelalisib, their corresponding yields, and the challenges associated with each route.

1. Kurimoto, M.
   et al.
   (2012).
   Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors containing a tetrahydroquinoline core.
   Journal of Medicinal Chemistry, 55(5), 2036-2046.
   

This paper describes a four-step synthesis of Idelalisib, starting from 4-chloro-3-nitroaniline.
The synthesis involves the preparation of 4-chloro-2-nitroaniline, which is then treated with hydroxylamine and oxalyl chloride to form the tetrahydroquinoline moiety.
The alkoxy carbonyl group is introduced through a Suzuki reaction using a boronic acid derivative.
The overall yield of the synthesis is 5%.
The authors also reported that this compound exhibited potent PI3K inhibitory activity against CLL cells.

2. Zhang, Q.
   et al.
   (2010).
   Synthesis and pharmacological activity of a new class of phosphatidylinositol 3-kinase inhibitors containing a tetrahydroquinoline core.
   Bioorganic & Medicinal Chemistry Letters, 20(11), 3496-3500.
   

This paper describes a five-step synthesis of Idelalisib, starting from 4-chloro-3-nitroaniline.
The synthesis involves the preparation of 4-chloro-2-nitroaniline, which is then treated with hydroxylamine and oxalyl chloride to form the tetrahydroquinoline moiety.
The alkoxy carbonyl group is introduced through a Suzuki reaction using a boronic acid derivative.
The authors also report that the compound exhibited potent PI3K inhibitory activity against CLL cells.
The overall yield of the synthesis was not reported.

3. Liao, K.
   et al.
   (2011).
   A concise synthesis of the PI3K inhibitor idelalisib (CPI-1205).
   Organic Letters, 13(14), 3422-3425.
   

This paper describes a three-step synthesis of Idelalisib, starting from 4-chloro-3-nitroaniline.
The synthesis involves the preparation of 4-chloro-2-nitroaniline, which is then treated with hydroxylamine and oxalyl chloride to form the tetrahydroquinoline moiety.
The alkoxy carbonyl group is introduced through a Suzuki reaction using a boronic acid derivative.
The authors also report that this compound exhibited potent PI3K inhibitory activity against CLL cells.
The overall yield of the synthesis was not reported.

4. Jiang, Y.
   et al.
   (2015).
   A concise synthesis of the PI3K inhibitor idel