Conversion of the Laboratory Synthetic Route of the N-Aryl-2-benzothiazolamine R116010 to a Manufacturing Method

Autor:	Ivan Vervest, Yolande Lang, Fons De Knaep, Bert Willemsens, Wim Albert Alex Aelterman, and Stef Leurs
Rok vydání:	2001
Předmět:	chemistry.chemical_classification Ketone medicine.drug_class Aryl Organic Chemistry Diastereomer Alcohol Combinatorial chemistry Chloride Aminoketone chemistry.chemical_compound chemistry Yield (chemistry) medicine Physical and Theoretical Chemistry Enantiomer medicine.drug
Zdroj:	Organic Process Research & Development. 5:467-471
ISSN:	1520-586X 1083-6160
Popis:	A facile and large-scale preparation of the antitumor agent R116010 has been developed. The new synthetic process requires four steps: (i) Friedel−Crafts reaction of N-phenyl-2-benzothiazolamine with 2-chloropropionyl chloride, (ii) conversion of the α-chloroketone into the corresponding α-(dimethylamino)ketone and resolution of the latter, (iii) reduction of the chiral aminoketone with resultant formation of the β-amino alcohol and finally (iv) conversion of the amino alcohol into the β-aminoimidazole R116010. The key strategic improvement is the crystallization-induced diastereomeric dynamic resolution of the aminoketone, leading to the chiral ketone in 90% yield and 90% enantiomeric purity. This new process improves the overall yield from 0.26 to 18.8% without tedious chromatographic separations and hazardous reaction conditions.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::d070b216ea956ef1b109ede9a14ced40 https://doi.org/10.1021/op0100201 Zobrazit plný text záznamu