1345866-84-3

Upstream product

• 56341-37-8 6-chloro-2-oxindole 
• 85070-48-0 2-fluoro-3-chlorobenzaldehyde 
• 41608-64-4 methyl 3-methoxy-4-aminobenzoate 
• 908027-64-5 6-chloro-3-[1-(3-chloro-2-fluorophenyl)-meth-(E)-ylidene]-1,3-dihydroindol-2-one 
• 1345866-83-2 4-{2-[3,3-dimethyl-but-(E)-ylideneamino]acetylamino}-3-methoxybenzoic acid methyl ester 
• 1419186-19-8 4-(2-aminoacetylamino)-3-methoxybenzoic acid methyl ester hydrochloride 

Downstream Products

• 1345866-73-0 4-{[(2'R,3'S,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidin]e-5'-carbonyl]-amino}-3-methoxy-benzoic acid 

Relevant academic research and scientific papers

Synthesis of a spiroindolinone pyrrolidinecarboxamide MDM2 antagonist

A practical synthesis of a spiroindolinone pyrrolidinecarboxamide MDM2 antagonist 2 is reported. Cycloaddition of dipolarophile 3 with imine 30 afforded a complex mixture of diastereomers that were isomerized to the desired stereoisomer 31 by heating the mixture in the presence of DBU. After hydrolysis, the resulting product was resolved with a chiral amine to give an enantiopure acid which was converted to the target product 2. The process has been scaled up to a multihundred-gram scale. In addition, an asymmetric synthesis of 31 catalyzed by AgOAc and a chiral phosphine ligand was developed to give enantiomerically enriched 31, which was also converted to enantiopure 2.