Practical Syntheses of the Adhesion Molecule Inhibitor ER-49890 and Its Stereoisomer

Practical synthetic routes to anti-[3-(10H-pyrazino[2,3-b][1,4]-benzothiazin-8-ylmethyl)-3-azabicyclo[3.3.1]non-9-yl]acetic acid (ER-49890, 1) and its syn-isomer are reported. The anti-(3-azabicyclo[3.3.1]non-9-yl)acetic acid side chain (anti-12) was synthesized stereoselectively using Pd/C hydrogenation in the presence of HCl. The syn-isomer (syn-12) was concisely obtained by crystallization as its oxalic acid salt from a 1:1 mixture of anti- and syn-isomers. The 10H-pyrazino[2,3-b][1,4]benzothiazine core (7) was prepared from commercially available 4-chloro-3-nitrobenzyl alcohol (13) in four steps and good yield.