Luzindole

Luzindole (N-0774), (N-acetyl-2-benzyltryptamine), is a drug used in scientific research to study the role of melatonin in the body. Luzindole acts as a selective melatonin receptor antagonist, with approximately 11- to 25-fold greater affinity for the MT2 over the MT1 receptor. In animal studies, it has been observed to disrupt the circadian rhythm as well as produce antidepressant effects.

Synthesis
Although the "hydrogen bomb" method was reported as 54% yield by Dubococvich, Boehringer Sohn achieved 96% for this step. The difference is that B.I. conducted their hydrogenation under normal pressure at 50°C for 5 hours, whereas Dubocovich conducted theirs at 100 lbs/in2 hydrogen heated to 35°C. This proves that the hydrogenation step proceeds favorably under milder conditions. The Pictet–Spengler reaction between tryptamine [61-54-1] (1) and benzaldehyde gives 1-Phenyl-tetrahydrocarboline [3790-45-2] (2). Catalytic hydrogenation leads to 2-Benzyltryptamine [22294-23-1] (3). Acylation with acetic anhydride only gave 21% yield of Luzindole (4). 2-iodoaniline [615-43-0] (1) Propargylbenzene [10147-11-2] (2) 2-(3-phenylprop-1-ynyl)aniline, PC85868179 (3) 2-benzylindole [3377-72-8] (4) 1-Dimethylamino-2-nitroethylene [1190-92-7] (5) (6)

One pot Luzindole synthesis: