A PRACTICAL SYNTHESIS OF NOVEL RHO-KINASE INHIBITOR, (S)-4-FLUORO-5-(2-METHYL-1,4-DIAZEPAN-1-YLSULFONYL)- ISOQUINOLINE

A practical synthesis of novel Rho-kinase inhibitor, (S)-4-fluoro-5-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline hydrochloride dihydrate (1) was achieved in a pilot-scale production. We have demonstrated the regioselective chlorosulfonylation of 4-fluoroisoquinoline in an one-pot reaction to afford 4-fluoroisoquinoline-5-sulfonyl chloride and the asymmetric construction of the (S)-2-methyl-1,4-diazepane moiety as key steps.