Method of preparation of physostigmine carbamate derivatives...

C - Chemistry – Metallurgy – 07 – D

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C07D 487/04 (2006.01)

Patent

CA 2100908

ABSTRACT OF THE DISCLOSURE This application relates to a new process for the preparation of a product of the formula Image (I) wherein R is loweralkyl; R1 is hydrogen, loweralkyl, lowercycloalkyl, lowercycloalkyllowerallyl, lowerbicycloalkyl, aryl or arylloweralkyl; R2 is loweralkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralkyl; or R1and R2 taken together with the nitrogen atom to which they are attached from a 3,4-dihydro-2(1H)-isoquinoline group; X is loweralkyl, loweralkoxy, halogen or trifluoromethyl; and m is 0,1 or 2; which proccss comprises (a) contacting a compound of formula II Image (II) wherein R, X and m are as defined above and R3 is loweralkyl, with base followed by a carboxylic acid of formula R5COOH wherein R5 is loweralkyl to afford a compound of formula III Image (III) wherein R, X and m are as defined above; (b) contacting the reaction mixture containing the compound of Formula III either (1) with an isocyanate of the formula R2NCO and obtaining a product of the formula I wherein R1 is hydrogen; or (2) with a compound of formula IV Image wherein R4 is hydrogen or loweralkyl in the presence of a carboxylic acid of theformula R5COOH wherein R5 is as above to afford a compound of formula V (V) Image wherein R, R4, X and m are as above; contacting the reaction mixture containing the compound of Formula V with a compound of the formula R1R2NH wherein R1 and R2 are as above; and isolating the product of Formula I.

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