合成路线1

Oxidation of 6-bromoisoquinoline (I) with meta-chloroperbenzoic acid, and subsequent addition of HCl provided the quinoline N-oxide hydrochloride (II). This was treated with POCl3 at 90 C to afford 6-bromo-1-chloroisoquinoline (III). Displacement of the chlorine atom of (III) for potassium phenoxide at 140 C gave phenyl ether (IV), which was subsequently reacted with ammonium acetate at 150 C to produce aminoisoquinoline (V). After protection of (V) as the benzamide (VI) by means of benzoic anhydride and pyridine, lithium-halogen exchange, followed by quenching with DMF furnished aldehyde (VII). Reduction of (VII) with NaBH4 gave alcohol (VIII). This was converted to chloride (IX) by conversion to the corresponding mesylate and further displacement with LiCl. Alkylation of (IX) with the sodium salt of N-Boc diethyl aminomalonate (X) yielded the isoquinolylmethyl malonate (XI). Hydrolysis and decarboxylation of (XI) with HCl in aqueous AcOH generated the amino acid (XII).