Conversion of the laboratory synthetic route of the N-aryl-2-benzothiazolamine R116010 to a manufacturing method

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 alpha -chloroketone into the corresponding alpha-(dimethylamino)ketone and resolution of the latter, (iii) reduction of the chiral aminoketone with resultant formation of the beta -amino alcohol and finally (iv) conversion of the amino alcohol into the beta -aminoiniidazole 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.