Maehr H, Zenchoff G, Coffen D L
Roche Research Center, Hoffmann La Roche Inc., Nutley, NJ 07110, USA.
Bioorg Med Chem. 1995 Apr;3(4):391-5. doi: 10.1016/0968-0896(95)00026-d.
An alternative synthesis of 7-chloro-N-methyl-5-(1H-pyrrol-2-yl)-3H-1,4-benzodiazepin-2-amine, the compound that inhibits gene expression by HIV-1 at the level of transcriptional transactivation by Tat, has been developed. The process is based on ring expansion of 6-chloro-2-chloromethyl-4-(1H-pyrrol-2-yl)quinazoline 3-oxide which leads to the corresponding benzodiazepine Ro24-7429. Quinazoline 3-oxide formation in the presence of boron trifluoride gives a tetracyclic system containing a 2,2-difluoro-1,3,6,2-oxadiazaborine ring that survives ring expansion to 13-chloro-5,5-difluoro-9-(methylamino)-5H-pyrrolo[1',2':3,4]- 1,3,6,2-oxadiazabora[6,5-d]-8H-1,4-benzodiazepin-7-ium hydroxide inner salt. This unusual benzodiazepine does not significantly inhibit Tat-mediated gene expression by HIV-1.
