Patent ID: 7964736

Claim:
A method of making a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; R 1 is —H or —P(═O)(OH) 2 ; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt thereof, comprising: contacting a compound having the formula: wherein L 1 is C 1 - C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R 2 is hydroxy, alkoxy, or aryloxy; R b is hydrogen or alkyl; and n is 0, 1, 2, 3, or 4; with a compound having the formula L 2 -CH 2 —CN, wherein L 2 is a leaving group, to form a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R 2 is hydroxy, alkoxy, or aryloxy; R b is hydrogen or alkyl; and n is 0, 1, 2, 3, or 4; converting compound (III) into a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R b is hydrogen or alkyl; L 3 is a leaving group; and R 3 is hydrogen, alkyl or aryl; and n is 0, 1, 2, 3, or 4; contacting compound (IV) with NH-R 4 to form a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R b is hydrogen or alkyl; R 4 is hydrogen, aralkyl or a protecting group; and n is 0, 1, 2, 3, or 4; converting compound (V) into a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R b is hydrogen or alkyl; R 4 is hydrogen, aralkyl or a protecting group; R 8 is hydrogen, alkyl, aryl, or a cation; and n is 0, 1, 2, 3, or 4; contacting compound (VI) with cyanogen bromide to form a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R b is hydrogen or alkyl; R 4 is hydrogen, aralkyl or a protecting group; R 8 is hydrogen, alkyl, aryl, or a cation; R c , is hydrogen alkyl, aralkyl, or a protecting group; and n is 0, 1, 2, 3, or 4; converting compound (VII) with into a compound having the formula: wherein L 1 is C 1 -C 4 alkylene; each R a , independently, is hydrogen, alkyl, alkoxy, aryl, aralkyl, hydroxy, or halo; R 4 is hydrogen, aralkyl or a protecting group; each R 8 , independently, is hydrogen, alkyl, aryl, or a cation; R c is hydrogen, alkyl, aralkyl, or a protecting group; and n is 0, 1, 2, 3, or 4; or a pharmaceutically acceptable salt thereof.