166883-20-1Relevant articles and documents
Efficient syntheses of AZD4407 via thioether formation by nucleophilic attack of organometallic species on sulphur
Alcaraz, Marie-Lyne,Atkinson, Stephanie,Cornwall, Philip,Foster, Alison C.,Gill, Duncan M.,Humphries, Lesley A.,Keegan, Philip S.,Kemp, Richard,Merifield, Eric,Nixon, Robert A.,Noble, Allison J.,O'Beirne, Darren,Patel, Zakariya M.,Perkins, Jacob,Rowan, Paul,Sadler, Paul,Singleton, John T.,Tornos, James,Watts, Andrew J.,Woodland, Ian A.
, p. 555 - 569 (2012/12/25)
The development of two efficient strategies for the synthesis of AZD4407 is reported, both of which are considered suitable for large-scale manufacture. In the first approach, 3-bromothiophene is coupled with (2S)-2- methyltetrahydropyran-4-one using Grignard chemistry. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulphur provides AZD4407 after acid-catalysed deprotection and epimerisation. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives. Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2- methyltetrahydropyran-4-one provides AZD4407 after acid-catalysed deprotection and epimerisation.
