Efficient syntheses of AZD4407 via thioether formation by nucleophilic attack of organometallic species on sulphur

…, AJ Noble, D O'Beirne, ZM Patel, J Perkins…

Index: 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. Organic Process Research and Development, 2005 , vol. 9, # 5 p. 555 - 569

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Citation Number: 66

Abstract

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 (2 S)-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 ...