Year: 2012
Type: article
Abstract: Some Items of Interest to Process R&D Chemists and Engineers ■ SYNTHESIS OF 2-CYANO-4-CHLOROPYRIDINESVeerareddy and co-workers of Suven Life Sciences have reported (J.Heterocycl.Chem.2011, 48, 961) an improved procedure for the synthesis of 2-cyano 4-chloropyridines.Such products are useful building blocks en route to more elaborate pyridines, e.g.via SnAr of the 4-chloro group or manipulation of the 2-cyano group.Thus, direct conversion of 4-nitropyridine N-oxides into 2-cyano-4-chloropyridines was achieved via sequential addition of trimethylsilylcyanide and ethyl chloroformate in dichloromethane under mild conditions.Whilst most yields were modest (10-48%), this chemistry provides an advantage over other approaches that are restricted to 2-methyl 4-nitropyridine-N-oxides or that use highly toxic dimethylcarbamyl chloride.acid reacted with 2 equiv of the diamine to yield a mixture of the mono-and bis-benzimidazoles. ■ PRACTICAL SYNTHESIS OF RHO-KINASE INHIBITORShibuya of Kowa Research laboratories and collaborators from Fuji Chemical (Heterocycles 2011, 83(8), 1771-1781) report a scaleable approach to a novel chiral analogue of the known kinase inhibitor Fasudil.Initial attempts to prepare chlorosulfonyl isoquinoline 4 via direct sulfonyation (c.H 2 SO 4 /SO 3 ) proved problematic due to handling issues with 1 (m.pt 20-25 °C) and the need to neutralise large volumes of excess H 2 SO 4 .Acceptable yields in the sulfonation step were achieved by conversion of preformed sulfate salt 2 in neat sulfur trioxide without additional sulfuric acid.One-pot sequential addition of SO 3 and SOCl 2 to 2 yielded a mixture of sulfonyl chloride isomers.The desired isomer 4 was then isolated after crystallisation.Subsequent reaction with L-alaninol installed the chiral side chain.Mesylation of 5 afforded an intermediate N-sulfonylaziridine which underwent ring-opening with aminopropanol.Recrystallisation of the oxalate salt 6 removed the isomer resulting from 1′ aziridine ring-opening.Ring closure under Mitsunobu conditions completed the synthesis in overall 24% yield and >99.9 ee.
DOI: 10.1021/op300014y
Authors: Ian Wilson, Wenyi Zhao, Dongbo Zhao, Aman A. Desai, Rodrigo Octavio M. A. de Souza, Sylvain Guizzetti, Trevor Laird
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W4240731996