Method B is carried out under reaction conditions amply described in literature wherein tertiary amines are formed by alkylation of a secondary amine with an alkyl halide, sulfate, phosphate, tosylate, or mesylate. The Formula IV and Formula V intermediates are preferably reacted in an inert liqui...
The R and S isomers of Formula I (when R12 and R13 are different) can be prepared from an appropriate chiral halide (or mesylate) II (see Chart B). The appropriate chiral halide (or mesylate) II is prepared from a chiral alcohol IV. The appropriate chiral alcohol IV can be prepared ...
(iii) --N+ R1-6X R1-6Y R1-6Z halide- where R1-6Z is: PA4 (A) --H, PA4 (B) C1 -C3 alkyl, where halide is: PA4 (C) --Cl, PA4 (D) --Br, and where R1-6X and R1-6Y are as defined above, (c) --CO--CH(amino acid)-NH2 where amino acid is: (i) --H, (...
The alcohol precursors to (X) and (XI) may be obtained by conventional alkyl halide coupling to the 8-azabicyclooctane benzamide intermediate (III). Finally, intermediate (IX) of Scheme D may be prepared by reaction of intermediate (III) with a nitrile of the form N≡CCH(R2)(CH2)mL, ...