合成路线1

Nitration of 5-bromoisoquinoline (I) using KNO3 in H2SO4 gave 5-bromo-8-nitroisoquinoline (II), which upon methylation with dimethyl sulfate was converted to the isoquinolinium salt (III). Subsequent reduction of (III) with NaBH4 in AcOH provided tetrahydroisoquinoline (IV). This was coupled with phenylboronic acid (V) in the presence of Pd(PPh3)4 and NaHCO3 to yield the 5-phenylisoquinoline (VI). Further reduction of the nitro group of (VI) by catalytic hydrogenation over Pd/C afforded amine (VII). The pyrroloisoquinoline (VIII) was then formed by condensation of (VII) with chloral and hydroxylamine in boiling water, followed by cyclization of the intermediate (oxymino)acetamide in methanesulfonic acid at 120 C. After chlorosulfonation of (VIII), the sulfonyl chloride (IX) was condensed with dimethylamine in THF to afford sulfonamide (X). Hydroxylamine derivative (XIV) was prepared by O-alkylation of N-hydroxyphthalimide (XI) with alpha-bromo-gamma-butyrolactone (XII), followed by hydrolysis of the phthalimide (XIII) in boiling 1 M HCl. Hydroxylamine derivative (XIV) was then condensed with sulfonamide (X) to furnish oxime (XV). Finally, hydrolysis of the butyrolactone group of (XV) with aqueous NaOH gave the title compound.