Process for preparing substituted benzimidazole compounds

1. A process for preparing compounds of formula X:

wherein:

R is selected from the group consisting of halo, hydroxy, azido, C 1-8 alkyl, trihalomethyl, C 1-8 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 6-14 arylC 2-6 alkenyl, C 6-14 arylC 2-6 alkynyl,

—NR 25 R 26 wherein R 25 and R 26 may be the same or different and are each independently selected from the group consisting of H, halo, C 1-8 alkyl, cyanoC 1-8 alkyl, hydroxyC 1-8 alkyl, haloC 1-8 alkyl, C 3-7 cycloalkyl, C 1-8 alkyl-C 3-7 cycloalkyl, C 2-6 alkenyl,C 3-7 cycloalkylC 1-8 alkyl, C 2-6 alkynyl, C 6-14 aryl, C 6-14 arylC 1-6 alkyl, heterocyclylC 1-8 alkyl, C 1-8 alkylcarbonyl, and C 6-14 aryl-sulfonyl;

—NHNR 30 R 31 wherein R 30 and R 31 are the same or different and are each independently C 1-6 alkyl;

—N═NNC 1-6 alkyl;

—NHOC 1-6 alkyl;

—OR 27 wherein R 27 is selected from the group consisting of C 1-8 alkyl, C 3-7 cyclo-alkyl, and C 6-14 aryl;

—SR 28 wherein R 28 is selected from the group consisting of H, C 1-8 alkyl, hydroxyC 1-8 alkyl, C 3-7 cycloalkyl, C 6-14 aryl, and C 6-14 arylC 1-6 alkyl;

R 15 is selected from the group consisting of H, halo, C 1-6 alkyl or C 2-6 alkenyl;

R 16 and R 17 may be the same or different and are each independently selected from the group consisting of H, halo, C 1-8 alkyl, C 6-14 aryl, heterocyclylC 1-8 aryl, C 1-8 alkoxy, haloC 1-8 alkyl, NO 2 , and SR 29 where R 29 is selected from the group consisting of H, C 1-8 alkyl, C 6-14 aryl or C 6-14 arylC 1-8 alkyl; and

R 20 is a D- or L- sugar moiety selected from the group consisting of:

wherein:

R 21 and R 22 may be the same or different and are each independently selected from the group consisting of H, hydroxy, protected hydroxy group, halo, C 1-8 alkyl, C 1-8 alkylhydroxy, haloC 1-8 alkyl, or C 1-8 alkoxy;

R 23 is selected from the group consisting of H, hydroxy, protected hydroxy group, C 1-8 alkyl, C 1-8 alkoxy, CH 2 R 32 wherein R 32 is hydroxy, protected hydroxy group, halo, or azido; and C(R 33 ) 3 wherein each R 33 is halo;

and wherein R 21 , R 22 and R 23 may be in the α- or β-position;

and pharmaceutically acceptable salts thereof; the process comprising the steps of:

(a) cyclizing a phenylenediamine of formula XI:

with carbonyl di-imidazole to yield a compound of formula XII:

(b) reacting the compound of formula XII with PO(X) 3 , wherein X is halo, to prepare a compound of formula XIII:

(c) reacting the compound of formula XIII with a 5- or 6-membered, D- or L- sugar selected from the group consisting of:

wherein

L is a leaving group in the α- or β- position to prepare compounds of formula X:

wherein R 15 , R 16 , R 17 ,are as defined above and R is halo, and pharmaceutically acceptable derivatives and prodrugs thereof; and

(d) optionally converting the compound of formula X or pharmaceutically acceptable derivative or prodrug thereof into a further compound of formula X or pharmaceutically acceptable derivative or prodrug thereof by nucleophilic substitution.