Xylamidine

The drug does not cross the blood–brain barrier and hence is peripherally selective, which makes it useful for blocking peripheral serotonergic responses like cardiovascular[3][4] and gastrointestinal effects,[5] without producing the central effects of 5-HT2A receptor blockade such as sedation, or interfering with the central actions of 5-HT2A receptor agonists.

[6] Xylamidine and analogues were patented for use in combination with serotonin 5-HT2A receptor agonists like serotonergic psychedelics in 2023.

It is prepared by alkylation of 3-methoxyphenol (m-methoxyphenol) with α-chloropropionitrile, potassium iodide, and potassium carbonate in butanone to give #, which is in turn reduced with lithium aluminium hydride to give the primary amine #.

When # is treated with m-tolylacetonitrile in the presence of anhydrous hydrochloric acid, the synthesis is completed.

Alternately, one can react primary amine # with m-tolylacetamidine under acid catalysis to produce xylamidine.