5-Methoxy-N,N-di-n-propyltryptamine (5-MeO-DPT): freebase and fumarate

The solid-state structure of the synthetic psychedelic 5-MeO-DPT is reported in its freebase form and as its fumarate salt.

1. Chemical context 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive indolealkylamine that is found in a number of plants and animals, but is best known to be present in the parotid glands of the Colorado River toad, Bufo alvarius (Shen et al., 2010). 5-MeO-DMT demonstrates high activity at the serotonin (5-hydroxytryptamine, 5-HT) 2A receptor, which leads to its psychotropic activity. Recent research has pointed to 5-MeO-DMT as a promising pharmaceutical in the treatment of mental health disorders (Uthaug et al., 2019). There are a number of synthetic N,N-dialkyl derivatives including 5-methoxy-N-methyl-N-isopropyltryptamin (5-MeO-MiPT), 5-methoxy-N,N-diethyltryptamine (5-MeO-DET), 5-methoxy-N,N-di-n-propyltryptamine (5-MeO-DPT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT). Alexander Shulgin described the experience associated with inhalation of these derivatives in humans, with 5-MeO-DMT described as 'positive and out-of-body' while 5-MeO-DPT was described as 'good and bad' (Shulgin & Shulgin, 1997). 5-MeO-DPT has not been described much in the scientific literature, though a recent report described its activity at the 5-HT 1A and 5-HT 2A receptors showing 75-100% of full agonism at both receptors (Å strand et al., 2020). As this class of compounds becomes more important for the treatment of mental health in humans, an in depth understanding of these compounds and how the structural changes impact the clinical experience in humans is going to be significant. To do so, it is important to have analytically pure, well-characterized ISSN 2056-9890 compounds, ideally as crystalline materials. Herein we report the first structures of 5-MeO-DPT, both as its freebase and as its fumarate salt.
The asymmetric unit of bis(5-methoxy-N,N-di-n-propyltryptammonium) fumarate contains one tryptammonium cation and half of a fumarate dianion (Fig. 1, right). The tryptammonium cation possesses a near planar indole unit with a deviation from planarity of 0.015 Å . The methoxy group is turned slightly from the plane of the indole ring with a C6-C5-O1-C17 torsion angle of À13.5 (4) . The ethylamino arm is turned away from the indole plane with a C1-C8-C9-C10 torsion angle of À104.8 (3) . The second half of the fumarate dianion is generated by inversion, and is near planar with an r.m.s. deviation from planarity of 0.022 Å .

Supramolecular features
In the solid-state structure of 5-MeO-DPT freebase, the molecules are held together by an N1-H1Á Á ÁN2 hydrogen bond between the indole N-H and the amino nitrogen atom. These hydrogen bonds join the molecules together in infinite chains along the [010] direction (Table 1). The crystal packing of 5-MeO-DPT freebase is shown on the left in Fig. 2.

Figure 1
The molecular structures of 5-MeO-DPT freebase (left) and 5-MeO-DPT fumarate (right), showing the atomic labeling. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines. Symmetry code: (i) 1 À x, 2 À y, 2 À z. The crystal packing of 5-MeO-DPT freebase (left), viewed along the a axis, and the crystal packing of 5-MeO-DPT fumarate (right), viewed along the a axis. The hydrogen bonds (Tables 1 and 2) are shown as dashed lines. Hydrogen atoms not involved in hydrogen bonds are omitted for clarity. metric unit through an N2-H2Á Á ÁO3 hydrogen bond between the ammonium nitrogen and a carboxylate oxygen of the fumarate. There is also an N1-H1Á Á ÁO4 hydrogen bond between the indole nitrogen and the other oxygen of the carboxylate group on a symmetry-generated fumarate dianion ( Table 2). The crystal packing of 5-MeO-DPT fumarate is shown on the right in Fig. 2. Two tryptammonium cations and two fumarate dianions are joined together through these hydrogen bonds to form rings with graph-set notation R 4 4 (22) (Etter et al., 1990). The rings are joined together by two parallel chains along [001]. These chains have graph-set notation C 2 2 (14) and C 4 4 (28). The chains and rings are shown in Fig. 3.

Synthesis and crystallization
Slow evaporation of an acetone solution of a commercial sample (Chem Logix) of 5-MeO-DPT freebase resulted in the formation of crystals of 5-methoxy-N,N-di-n-propyltryptamine suitable for X-ray analysis. Crystals of bis(5methoxy-N,N-di-n-propyltryptammonium) fumarate were grown from the slow evaporation of an acetonitrile solution of a commercial sample (Chem Logix) of 5-MeO-DPT fumarate.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.

Figure 3
The hydrogen-bonding network along [001], which consists of R 4 4 (22) rings that are joined together by two parallel C 2 2 (14) and C 4 4 (28) chains. The three components described in graph-set notation and the combined chain is shown. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms not involved in hydrogen bonding are omitted for clarity. Hydrogen bonds are shown as dashed lines.