851724-01-1

Upstream product

• 61-70-1 N-methyl-2-indolinone 
• 1147550-11-5 ammonium thiocyanate 
• 166883-20-1 1-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl chloride 
• 166883-22-3 5-mercapto-1-methylindolin-2-one 

Relevant academic research and scientific papers

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

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.

Ferric(III) chloride-promoted electrophilic thiocyanation of aromatic and heteroaromatic compounds

Indoles, oxindoles and aromatic amino compounds undergo smooth thiocyanation with ammonium thiocyanate in the presence of anhydrous FeCl 3 in dichloromethane under mild conditions to afford the corresponding 3-indolyl and 4-aryl thiocyanates, respectively, in high yields with excellent selectivity. The use of ferric chloride makes it quite simple, more convenient and practical. This new method offers several advantages such as high conversions, cleaner reaction profiles, short reaction times, and the use of inexpensive and readily available catalyst. Georg Thieme Verlag Stuttgart.