Process for preparing substituted benzimidazole compounds
The invention relates to new methods of preparing substituted benzimidazole compounds, such as 2-bromo-5,6-dichlorobenzimidazole, which are useful in the preparation of compounds having antiviral activity.
1. A process for preparing a compound of formula VII:
wherein:
R is —NR 8 R 9 where R 8 and R 9 are each independently selected from the group consisting of H, C 1-6 alkyl, cyanoC 1-6 alkyl, hydroxyC 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkylC 3-7 cycloalkyl, C 2-6 alkenyl, C 3-7 cycloalkylC 1-6 alkyl, C 2-6 alkynyl, aryl, arylC 1-6 alkyl, and COC 1-6 alkyl; and
each R 10 is independently selected from the group consisting of hydroxy and protected hydroxy group;
or a pharmaceutically acceptable derivative or prodrug thereof;
said process comprising the steps of:
(a) cyclizing 4,5-dichloro-o-phenylenediamine with carbonyl di-imidazole to yield a compound of formula II:
(b) reacting the compound of formula II with PO(X) 3 wherein X is halo, to prepare a compound of formula I:
(c) reacting the compound of formula I with a furanosyl of formula III:
to prepare a compound of formula V:
(d) reacting the compound of formula V with an amine of formula H—NR 8 R 9 ;
to prepare a compound of formula VII or a pharmaceutically acceptable derivative or prodrug thereof.
2. The process according to claim 1 , wherein one or more of R 10 is protected hydroxy group and said process further comprises the step of removing any protecting groups.
3. The process according to claim 1 , wherein R is isopropylamino and the furanosyl moiety:
is β-L-ribofuranosyl.