66303-55-7Relevant articles and documents
Scalable asymmetric synthesis of a key fragment of Bcl-2/Bcl-xLinhibitors
Laclef, Sylvain,Taillier, Catherine,Penloup, Christine,Viger, Aurélie,Brière, Jean-Fran?ois,Hardouin, Christophe,Levacher, Vincent
, p. 39817 - 39821 (2014)
The asymmetric synthesis of a 1,3-diamine building block for the elaboration of Bcl-2 and Bcl-xLprotein inhibitors is described through two key steps: (1) a highly diastereoselective aza-Reformatsky reaction, and (2) a chemoselective amination under Mitsunobu conditions. This synthetic sequence was also demonstrated to be successfully amenable to a large-scale synthesis. This journal is
PROCESS FOR PREPARING SULFONAMIDE COMPOUNDS
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, (2020/09/03)
Provided are a process for preparing a sulfonamide compound which is an inhibitor of Bcl-2/Bcl-xL, including the compound (3R) -1- (3- (4- (4- (4- (3- (2- (4-chlorophenyl) -1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl) -5-fluorophenyl) piperazine
Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-xL Antagonist. 2. Manufacture of the 1,3-Diamine Moiety and Improvement of the Final Coupling Reaction
Hardouin, Christophe,Baillard, Sandrine,Barière, Fran?ois,Craquelin, Anthony,Grandjean, Mathieu,Janvier, Solenn,Le Roux, Stéphane,Penloup, Christine,Russo, Olivier
, p. 670 - 685 (2019/12/24)
This paper describes the synthesis of kilogram quantities of the sulfonamide moiety 3 involved in a coupling reaction with acid moiety 2 to provide batches of drug candidate 1 for preclinical studies and first-in-human clinical trials. A first approach relying on a chiral separation furnished the desired enantiomer of 1,3-diamine 20, precursor of sulfonamide 3. An enantiomeric synthesis of 20 using the Ellman's chiral auxiliary coupled with an aza-Reformatsky reaction to control the stereochemistry is also discussed. Coupling conditions of the final step involving EDCI to provide 1 under a cGMP process are detailed. An alternative approach using N-(1-methanesulfonyl)benzotriazole is also presented.