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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoIUCrDATA
ISSN: 2414-3146
Volume 8| Part 9| September 2023| x230779
https://doi.org/10.1107/S2414314623007794

Bis(4-acet­oxy-N-ethyl-N-n-propyl­tryptammonium) fumarate–fumaric acid (1/1)

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Duyen N. K. Pham,a Nathan B. Sackett,b Andrew R. Chadeayne,c James A. Golena and David R. Mankea*

aUniversity of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747, USA, bUniversity of Washington, Department of Psychiatry & Behavioral Sciences, Center for Novel Therapeutics in Addiction Psychiatry, 1959 NE Pacific Street, Box 356560, Seattle, WA 98195, USA, and cCaaMTech, Inc., 58 East Sunset Way, Suite 209, Issaquah, WA 98027, USA
*Correspondence e-mail: dmanke@umassd.edu

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 29 August 2023; accepted 6 September 2023; online 8 September 2023)

The solid-state structure of the title salt/adduct (systemic name: bis­{[2-(4-acet­yloxy-1H-indol-3-yl)eth­yl](eth­yl)propyl­aza­nium} but-2-enedioate–(E)-butenedioic acid (1/1)), 2C17H25N2O2+·C4H2O42−·C4H4O4, was determined by single-crystal X-ray diffraction. The asymmetric unit consists of a singly protonated tryptammonium cation, one half of a fumarate dianion and one half of a fumaric acid mol­ecule. In the crystal, the ions and mol­ecules are linked together in infinite chains propagating along [001] through a series of N—H⋯O and O—H⋯O hydrogen bonds.

CCDC reference: 2293403

Similar articles
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[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Psilocybin (4-phosphor­yloxy-N,N-di­methyl­tryptamine) is a natural product found in many species of mushrooms. It functions as a prodrug of psilocin (4-hy­droxy-N,N-di­methyl­tryptamine) via enzymatic hydrolysis of the phosphor­yloxy group to generate the active psychedelic. Psilocin is an agonist at serotonin (5-hy­droxy­tryptamine; 5-HT) receptors, most notably the serotonin 2A (5-HT2A) receptor, which is primarily responsible for the psychoactive and therapeutic effects of the mol­ecule. Psilocybin has shown promise in the treatment of pervasive human disorders, including depression (Carhart-Harris et al., 2021[Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D. & Nutt, D. J. (2021). N. Engl. J. Med. 384, 1402-1411.]; Davis et al., 2021[Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H. & Griffiths, R. R. (2021). JAMA Psychiatry 78, 481-489.]; von Rotz et al., 2023[Rotz, R. von, Schindowski, E. M., Jungwirth, J., Schudlt, A., Rieser, N. M., Zahoranszky, K., Seifritz, E., Nowak, A., Nowak, P., Jäncke, L., Preller, K. H. & Vollenweider, F. X. (2023). EClinicalMedicine, 56, 101809.]), end-of-life anxiety (Grob et al., 2011[Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L. & Greer, G. (2011). Arch. Gen. Psychiatry, 68, 71-78.]; Griffiths et al., 2016[Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P. & Klinedinst, M. A. (2016). J. Psychopharmacol. 30, 1181-1197.]), obsessive-compulsive disorders (Moreno et al., 2006[Moreno, F. A., Wiegand, C. B., Taitano, E. K. & Delgado, P. L. (2006). J. Clin. Psychiatry, 67, 1735-1740.]), tobacco-use disorder (Johnson et al., 2014[Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. & Griffiths, R. R. (2014). J. Psychopharmacol. 28, 983-992.]) and alcohol-use disorder (Bogenschutz et al., 2022[Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehims, A. A., Laska, E., Mennenga, S. E., O'Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S. & Worth, L. (2022). JAMA Psychiatry 79, 953-962.]). The inter­est in psilocybin has also generated inter­est in the structure–activity relationship (SAR) of analogous compounds.

We previously reported two crystalline forms of psilacetin (4-acet­oxy-N,N-di­methyl­tryptamine) which, like psilocybin, also functions as a prodrug of psilocin. Our recent in vivo studies in mice demonstrate that psilacetin is more efficient than psilocybin at delivering psilocin, resulting in increased potency at equimolar amounts. This is supported by background hydrolysis rates which show psilacetin to hydrolyze forty times faster than psilocybin, but also demonstrate that the hydrolysis of either prodrug in the body must be enzymatic (Glatfelter et al., 2022b[Glatfelter, G. C., Pottie, E., Partilla, J. S., Sherwood, A. M., Kaylo, K., Pham, D. N. K., Naeem, M., Sammeta, V. R., DeBoer, S., Golen, J. A., Hulley, E. B., Stove, C. P., Chadeayne, A. R., Manke, D. R. & Baumann, M. H. (2022b). ACS Pharmacol. Transl. Sci. 5, 1181-1196.]). 4-Acet­oxy-N-ethyl-N-n-propyl­tryptamine (4-AcO-EPT) is a putative prodrug of the synthetic psychedelic, and psilocin analogue, 4-hy­droxy-N-ethyl-N-n-propyl­tryptamine (4-HO-EPT). When competitive binding assays are compared, binding is observed for 4-HO-EPT across many more receptors than 4-AcO-EPT, and significantly stronger binding is observed at most receptors where 4-AcO-EPT is also competitive (Glatfelter et al., 2023[Glatfelter, G. C., Naeem, M., Pham, D. N. K., Golen, J. A., Chadeayne, A. R., Manke, D. R. & Baumann, M. H. (2023). ACS Pharmacol. Transl. Sci. 6, 567-577.]). 4-HO-EPT showed a substantial increase in in vitro functional assays for 5-HT2A agonism over 4-AcO-EPT, with an observed EC50 of 4.24 nM, compared to an EC50 of 24.0 nM for the ester.

One thing that is not clear from the in vitro and in vivo studies of 4-AcO-EPT is the exact chemical composition of the experimentally studied compound. Klein et al. reported in vitro and in vivo data for `4-AcO-EPT fumarate', which describes a doubly deprotonated di­carb­oxy­lic acid and a 2:1 molar ratio of tryptamine to fumaric acid equivalent. However, the mol­ecular weight calculations in the paper indicate that the compound studied had a 1:1 ratio of tryptamine to fumaric acid, i.e. 4-AcO-EPT hydro­fumarate. In our prior study, we reported 4-AcO-EPT hydro­fumarate based upon NMR data demonstrating a 1:1 ratio of tryptamine to fumaric acid equivalent, consistent with a singly deprotonated di­carb­oxy­lic acid for each tryptamine. However, this work reveals an error in this assignment, further highlighting the necessity of isolating a single crystal and performing diffraction studies when determining the exact nature of crystalline tryptamine solids. Herein we report the compound to be neither the fumarate nor the hydro­fumarate, but rather bis­(4-acet­oxy-N-ethyl-N-n-propyl­tryptammonium) fumarate–fumaric acid.

The mol­ecular structure of 4-AcO-EPT fumarate–fumaric acid is shown in Fig. 1[link]. The asymmetric unit contains one 4-acet­oxy-N-ethyl-N-n-propyl­tryptammonium (C17H25N2O2+) cation, one half of a fumarate (C2HO2−) dianion, and one half of a fumaric acid (C2H2O2) mol­ecule. The indole ring system of the cation is near planar with a r.m.s. deviation from planarity of 0.018 Å. The ethyl­amino arm is disordered over two orientations in a 0.895 (7):0.105 (7) ratio. The major component of the ethyl­amino arm is nearly co-planar with the indole ring, showing a C7—C8—C9—C10 torsion angle of −176.3 (2)°. The ethyl and n-propyl groups are disordered over two sets of sites with a 0.741 (6):0.259 (6) ratio, with the methyl­ene carbon atoms of the n-propyl groups being in close proximity to the two ethyl group C atoms. The complete fumarate dianion is generated through crystallographic inversion symmetry, and is near planar with an r.m.s. deviation from planarity of 0.009 Å. The complete fumaric acid dianion in generated similarly and only slightly less planar with an r.m.s. deviation of 0.070 Å.

[Figure 1]
Figure 1
The mol­ecular structure of 4-AcO-EPT fumarate–fumaric acid showing the atomic labeling. Displacement ellipsoids are shown at the 50% probability level. Dashed bonds indicate a disordered component in the structure. Hydrogen bonds are shown as dashed lines. Symmetry codes: (i) −x, −y, 1 − z; (ii) −x, −y, 2 − z.

In the extended structure, the 4-acet­oxy-N-ethyl-N-n-propyl­tryptammonium cations, fumarate dianions and neutral fumaric acid mol­ecules are linked together in infinite one-dimensional chain propagating along [001]. The tryptammonium cations are linked to the fumarate dianions through N2—H2⋯O5 hydrogen bonds, and the fumaric acid mol­ecules are linked to the fumarate dianions through O4—H4A⋯O6 hydrogen bonds (Table 1[link]). The packing of 4-AcO-EPT fumarate–fumaric acid is shown in Fig. 2[link].

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O4—H4A⋯O6 0.89 (1) 1.65 (1) 2.531 (2) 168 (3)
N2—H2⋯O5i 0.88 (1) 1.89 (1) 2.757 (2) 166 (2)
Symmetry code: (i) [x, y-1, z+1].
[Figure 2]
Figure 2
The crystal packing of the title compound viewed along the b axis. The hydrogen bonds are shown as dashed lines. Hydrogen atoms not involved in hydrogen bonds are omitted for clarity. Only one component of disorders are shown.

In addition to the structure reported here, there have been ten other 4-acet­oxy­tryptamine structures reported in the literature, which include one mono­alkyl­tryptamine, 4-acet­oxy-N-methyl­tryptamine as its chloride salt (Glatfelter et al., 2022b[Glatfelter, G. C., Pottie, E., Partilla, J. S., Sherwood, A. M., Kaylo, K., Pham, D. N. K., Naeem, M., Sammeta, V. R., DeBoer, S., Golen, J. A., Hulley, E. B., Stove, C. P., Chadeayne, A. R., Manke, D. R. & Baumann, M. H. (2022b). ACS Pharmacol. Transl. Sci. 5, 1181-1196.]), five di­alkyl­trypamines 4-acet­oxy-N,N-di­methyl­tryptamine as its hydro­fumarate (Chadeayne et al., 2019b[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019b). Psychedelic Science Review, https://psychedelicreview. com/the-crystal-structure-of-4-aco-dmt-fumarate/]) and fumarate (Chadeayne et al., 2019a[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019a). Acta Cryst. E75, 900-902.]) salts, 4-acet­oxy-N-methyl-N-ethyl­tryptamine and 4-acet­oxy-N-methyl-N-allyl­tryptamine as hydro­fumarate salts, and 4-acet­oxy-N,N-di­allyl­tryptamine as a fumarate-fumaric acid structure similar to that reported in this manuscript (Pham et al., 2021[Pham, D. N. K., Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2021). Acta Cryst. E77, 101-106.]). There are four tri­alkyl­tryptamine structures reported, 4-acet­oxy-N,N,N-tri­methyl­tryptamine (Chadeayne et al., 2020[Chadeayne, A. R., Pham, D. N. K., Reid, B. G., Golen, J. A. & Manke, D. R. (2020). ACS Omega, 5, 16940-16943.]), 4-acet­oxy-N,N-dimethyl-N-n-propyl­tryptamine, 4-acet­oxy-N,N-dimethyl-N-iso­propyl­tryptamine, 4-acet­oxy-N,N-dimethyl-N-ethyl­tryptamine all as their iodide salts (Glatfelter et al., 2022a[Glatfelter, G. C., Pham, D. N. K., Walther, D., Golen, J. A., Chadeayne, A. R., Baumann, M. H. & Manke, D. R. (2022a). ACS Omega, 7, 24888-24894.]). There are also three other 4-carb­oxy­lic ester prodrug structure reported, which are 4-propion­oxy-N,N-di­methyl­tryptamine as its hydro­fumarate salt (Glatfelter et al., 2023[Glatfelter, G. C., Naeem, M., Pham, D. N. K., Golen, J. A., Chadeayne, A. R., Manke, D. R. & Baumann, M. H. (2023). ACS Pharmacol. Transl. Sci. 6, 567-577.]) and two structures of the zwitterionic 4-glutarato-N,N-diiso­propyl­tryptamine (Naeem et al., 2022[Naeem, M., Bauer, B. E., Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2022). Acta Cryst. E78, 1034-1038.]).

Synthesis and crystallization

Crystals of bis­(N-ethyl-N-n-propyl­tryptammonium) fumarate–fumaric acid were grown from the slow evaporation of an aqueous solution of `4-AcO-EPT fumarate' obtained from ChemLogix.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. Atoms H1, H2 and H4A were found from a Fourier difference map and allowed to refine with restrained N—H distances of 0.87 (1) Å and 1.20 Ueq of parent N atoms, and O—H distances of 0.88 (1) Å and 1.50 Ueq of parent O atoms. All other hydrogen atoms were placed in calculated positions with appropriate riding parameters. Ethyl and propyl groups showed overlap disorder with respect to each other and were treated using SADI C—C distance restrains, DELU rigid body restraints, and ISOR isotropic restraints.

Table 2
Experimental details

Crystal data
Chemical formula C17H25N2O2+·0.5C4H2O42−·0.5C4H4O4
Mr 404.45
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 297
a, b, c (Å) 8.7642 (8), 10.8653 (9), 12.6564 (11)
α, β, γ (°) 65.094 (3), 75.354 (3), 76.718 (3)
V (Å3) 1047.12 (16)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.09
Crystal size (mm) 0.22 × 0.2 × 0.12
 
Data collection
Diffractometer Bruker D8 Venture CMOS
Absorption correction Multi-scan (SADABS; Krause et al., 2015[Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3-10.])
Tmin, Tmax 0.721, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections 28835, 4251, 3227
Rint 0.041
(sin θ/λ)max (Å−1) 0.626
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.056, 0.137, 1.03
No. of reflections 4251
No. of parameters 341
No. of restraints 115
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.35, −0.22
Computer programs: APEX3 and SAINT (Bruker, 2018[Bruker (2018). APEX3 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2014/5 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2019/3 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]), and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data

CCDC reference: 2293403

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314623007794/hb4447sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314623007794/hb4447Isup2.hkl

checkCIF report


Computing details top

Data collection: APEX 3 (Bruker, 2018); cell refinement: SAINT (Bruker, 2018); data reduction: SAINT (Bruker, 2018); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2019/3 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

Bis{[2-(4-acetyloxy-1H-indol-3-yl)ethyl](ethyl)propylazanium} but-2-enedioate–(E)-butenedioic acid (1/1) top
Crystal data top
C17H25N2O2+·0.5C4H2O42−·0.5C4H4O4Z = 2
Mr = 404.45F(000) = 432
Triclinic, P1Dx = 1.283 Mg m−3
a = 8.7642 (8) ÅMo Kα radiation, λ = 0.71073 Å
b = 10.8653 (9) ÅCell parameters from 8239 reflections
c = 12.6564 (11) Åθ = 2.8–26.3°
α = 65.094 (3)°µ = 0.09 mm−1
β = 75.354 (3)°T = 297 K
γ = 76.718 (3)°BLOCK, colourless
V = 1047.12 (16) Å30.22 × 0.2 × 0.12 mm
Data collection top
Bruker D8 Venture CMOS
diffractometer		3227 reflections with I > 2σ(I)
φ and ω scansRint = 0.041
Absorption correction: multi-scan
(SADABS; Krause et al., 2015)		θmax = 26.4°, θmin = 2.8°
Tmin = 0.721, Tmax = 0.745h = −10→10
28835 measured reflectionsk = −13→13
4251 independent reflectionsl = −15→15
Refinement top
Refinement on F2115 restraints
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.056H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.137 w = 1/[σ2(Fo2) + (0.0482P)2 + 0.5076P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
4251 reflectionsΔρmax = 0.35 e Å−3
341 parametersΔρmin = −0.22 e Å−3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.27647 (17)−0.80720 (14)1.03014 (13)0.0591 (4)
O20.5398 (2)−0.8121 (2)0.97964 (16)0.0830 (6)
O30.1315 (2)−0.02323 (17)0.80306 (14)0.0773 (5)
O4−0.0658 (2)0.14933 (15)0.76151 (12)0.0627 (4)
H4A−0.024 (3)0.168 (3)0.6856 (11)0.094*
O50.1155 (2)0.21798 (14)0.36799 (12)0.0647 (4)
O60.0480 (2)0.23432 (14)0.54237 (12)0.0604 (4)
N10.1435 (3)−0.3427 (2)0.82261 (18)0.0772 (6)
H10.096 (3)−0.272 (2)0.772 (2)0.093*
N20.2880 (2)−0.56997 (17)1.29957 (15)0.0529 (4)
H20.220 (2)−0.6296 (18)1.3266 (19)0.063*
C10.1785 (3)−0.3645 (2)0.9298 (2)0.0744 (7)
H1A0.169952−0.2963920.9580250.089*
C20.1695 (2)−0.4643 (2)0.80871 (18)0.0583 (6)
C30.1561 (3)−0.4964 (3)0.71526 (19)0.0694 (7)
H30.123104−0.4286230.6470120.083*
C40.1927 (3)−0.6296 (3)0.7277 (2)0.0700 (7)
H40.187362−0.6525300.6658530.084*
C50.2379 (3)−0.7321 (3)0.8300 (2)0.0629 (6)
H50.259661−0.8227870.8367920.075*
C60.2508 (2)−0.7010 (2)0.92117 (17)0.0508 (5)
C70.2216 (2)−0.5657 (2)0.91297 (16)0.0491 (5)
C80.2275 (3)−0.5003 (2)0.98849 (17)0.0558 (5)
C90.2847 (3)−0.5751 (2)1.10637 (19)0.0527 (8)0.895 (7)
H9A0.223769−0.6501321.1552490.063*0.895 (7)
H9B0.395507−0.6140591.0924680.063*0.895 (7)
C100.2694 (4)−0.4845 (3)1.17281 (19)0.0490 (8)0.895 (7)
H10A0.350332−0.4241091.1350080.059*0.895 (7)
H10B0.165866−0.4282101.1706020.059*0.895 (7)
C9A0.182 (3)−0.524 (3)1.1193 (10)0.069 (8)0.105 (7)
H9AA0.093424−0.4561131.1306310.083*0.105 (7)
H9AB0.149277−0.6138871.1642530.083*0.105 (7)
C10A0.320 (2)−0.514 (3)1.1640 (9)0.089 (12)0.105 (7)
H10C0.337116−0.4196071.1323790.107*0.105 (7)
H10D0.415098−0.5666341.1367720.107*0.105 (7)
C110.4486 (5)−0.6529 (6)1.3152 (4)0.0547 (11)0.741 (6)
H11A0.528096−0.5916401.2858110.066*0.741 (6)
H11B0.474027−0.7088991.2685500.066*0.741 (6)
C120.4558 (6)−0.7450 (5)1.4437 (4)0.0717 (12)0.741 (6)
H12A0.365280−0.7951791.4776800.086*0.741 (6)
H12B0.450747−0.6895651.4881220.086*0.741 (6)
C130.6093 (5)−0.8451 (4)1.4525 (4)0.1003 (16)0.741 (6)
H13A0.605799−0.9113711.5322800.150*0.741 (6)
H13B0.697996−0.7961601.4306370.150*0.741 (6)
H13C0.620986−0.8910821.4000400.150*0.741 (6)
C140.2341 (7)−0.4813 (5)1.3701 (4)0.0505 (10)0.741 (6)
H14A0.215332−0.5402271.4534310.061*0.741 (6)
H14B0.133039−0.4269051.3506440.061*0.741 (6)
C150.3488 (6)−0.3845 (5)1.3515 (5)0.0649 (12)0.741 (6)
H15A0.300869−0.3276871.3955300.097*0.741 (6)
H15B0.372168−0.3279441.2688450.097*0.741 (6)
H15C0.445657−0.4371611.3783030.097*0.741 (6)
C11A0.266 (3)−0.493 (2)1.3766 (17)0.090 (7)0.259 (6)
H11C0.282534−0.5537501.4561430.108*0.259 (6)
H11D0.160829−0.4399511.3804420.108*0.259 (6)
C12A0.394 (2)−0.3992 (17)1.3153 (14)0.077 (4)0.259 (6)
H12C0.499877−0.4507861.3121860.093*0.259 (6)
H12D0.378019−0.3368851.2359010.093*0.259 (6)
C13A0.3632 (14)−0.3249 (12)1.3981 (10)0.084 (3)0.259 (6)
H13D0.442001−0.2651901.3734270.125*0.259 (6)
H13E0.368967−0.3905071.4771880.125*0.259 (6)
H13F0.259198−0.2718061.3960390.125*0.259 (6)
C14A0.439 (2)−0.671 (2)1.3038 (19)0.100 (9)0.259 (6)
H14C0.526145−0.6168571.2658090.121*0.259 (6)
H14D0.437114−0.7167481.2530280.121*0.259 (6)
C15A0.487 (3)−0.783 (2)1.4176 (17)0.129 (8)0.259 (6)
H15D0.480279−0.8710081.4194870.194*0.259 (6)
H15E0.416676−0.7694761.4845960.194*0.259 (6)
H15F0.594408−0.7795071.4201760.194*0.259 (6)
C160.4261 (3)−0.8539 (2)1.0513 (2)0.0568 (5)
C170.4260 (4)−0.9596 (2)1.1741 (2)0.0785 (7)
H17A0.346455−0.9282641.2284380.118*
H17B0.528807−0.9748561.1947620.118*
H17C0.402813−1.0437241.1779250.118*
C180.0174 (3)0.0486 (2)0.83333 (17)0.0506 (5)
C19−0.0428 (3)0.0340 (2)0.95887 (17)0.0524 (5)
H19−0.1451380.0751990.9787940.063*
C200.0593 (2)0.17179 (18)0.47610 (16)0.0453 (4)
C210.0000 (2)0.03642 (17)0.52990 (15)0.0434 (4)
H21−0.0393880.0019390.6107810.052*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0588 (9)0.0495 (8)0.0537 (8)−0.0130 (7)−0.0083 (7)−0.0035 (6)
O20.0573 (10)0.0979 (13)0.0694 (11)−0.0046 (9)−0.0113 (8)−0.0121 (10)
O30.0949 (13)0.0707 (10)0.0511 (9)0.0132 (9)−0.0160 (9)−0.0199 (8)
O40.0790 (11)0.0586 (9)0.0415 (8)−0.0005 (8)−0.0137 (7)−0.0136 (7)
O50.0983 (12)0.0531 (8)0.0384 (7)−0.0426 (8)0.0083 (7)−0.0087 (6)
O60.0938 (11)0.0453 (8)0.0433 (8)−0.0271 (7)−0.0052 (7)−0.0133 (6)
N10.0837 (15)0.0567 (12)0.0508 (12)0.0138 (10)−0.0049 (10)0.0016 (9)
N20.0529 (10)0.0473 (9)0.0487 (9)−0.0206 (7)−0.0061 (8)−0.0041 (7)
C10.0951 (19)0.0511 (12)0.0548 (14)−0.0016 (12)0.0072 (12)−0.0151 (10)
C20.0460 (11)0.0620 (13)0.0434 (11)0.0019 (9)−0.0040 (9)−0.0049 (9)
C30.0475 (12)0.102 (2)0.0396 (11)−0.0074 (12)−0.0119 (9)−0.0088 (12)
C40.0571 (14)0.100 (2)0.0534 (13)−0.0204 (13)−0.0075 (11)−0.0270 (13)
C50.0560 (13)0.0737 (14)0.0624 (14)−0.0216 (11)−0.0037 (10)−0.0270 (12)
C60.0431 (10)0.0546 (11)0.0450 (11)−0.0123 (8)−0.0076 (8)−0.0072 (9)
C70.0442 (10)0.0512 (11)0.0377 (10)−0.0062 (8)−0.0053 (8)−0.0051 (8)
C80.0665 (13)0.0468 (11)0.0402 (10)−0.0101 (9)0.0004 (9)−0.0079 (8)
C90.0639 (17)0.0400 (12)0.0419 (12)−0.0031 (10)−0.0032 (10)−0.0096 (9)
C100.0513 (16)0.0403 (12)0.0436 (13)−0.0108 (11)0.0010 (10)−0.0080 (10)
C9A0.068 (11)0.075 (11)0.070 (11)−0.018 (8)−0.013 (8)−0.028 (8)
C10A0.070 (13)0.094 (15)0.092 (15)−0.033 (9)−0.031 (9)−0.004 (9)
C110.0516 (19)0.0473 (18)0.058 (2)−0.0096 (14)−0.0113 (15)−0.0116 (17)
C120.066 (2)0.073 (2)0.063 (2)0.0052 (19)−0.0225 (18)−0.0152 (19)
C130.077 (3)0.088 (3)0.094 (3)0.008 (2)−0.025 (2)0.001 (2)
C140.057 (2)0.0467 (17)0.0506 (19)−0.0126 (15)−0.0136 (16)−0.0163 (14)
C150.064 (3)0.057 (2)0.085 (3)−0.0126 (18)−0.019 (2)−0.033 (2)
C11A0.082 (9)0.097 (9)0.095 (9)−0.022 (5)−0.027 (5)−0.028 (5)
C12A0.081 (7)0.071 (6)0.079 (6)−0.020 (4)−0.015 (5)−0.024 (4)
C13A0.089 (7)0.081 (6)0.082 (7)−0.016 (5)−0.014 (5)−0.032 (5)
C14A0.115 (10)0.089 (9)0.106 (9)−0.035 (5)−0.011 (5)−0.040 (5)
C15A0.134 (12)0.127 (11)0.113 (10)0.023 (9)−0.024 (8)−0.053 (7)
C160.0644 (14)0.0473 (11)0.0556 (12)−0.0028 (10)−0.0133 (11)−0.0178 (9)
C170.101 (2)0.0540 (13)0.0629 (15)0.0052 (13)−0.0234 (14)−0.0089 (11)
C180.0631 (13)0.0458 (10)0.0445 (11)−0.0113 (9)−0.0088 (9)−0.0173 (9)
C190.0596 (12)0.0467 (11)0.0471 (11)−0.0105 (9)−0.0083 (9)−0.0135 (8)
C200.0537 (11)0.0373 (9)0.0385 (10)−0.0149 (8)−0.0042 (8)−0.0064 (8)
C210.0521 (10)0.0389 (9)0.0312 (9)−0.0166 (8)−0.0007 (8)−0.0042 (7)
Geometric parameters (Å, º) top
O1—C61.408 (2)C10A—H10D0.9700
O1—C161.343 (3)C11—H11A0.9700
O2—C161.194 (3)C11—H11B0.9700
O3—C181.206 (3)C11—C121.518 (5)
O4—H4A0.889 (10)C12—H12A0.9700
O4—C181.299 (2)C12—H12B0.9700
O5—C201.250 (2)C12—C131.518 (5)
O6—C201.258 (2)C13—H13A0.9600
N1—H10.869 (10)C13—H13B0.9600
N1—C11.377 (3)C13—H13C0.9600
N1—C21.366 (3)C14—H14A0.9700
N2—H20.880 (10)C14—H14B0.9700
N2—C101.507 (3)C14—C151.526 (5)
N2—C10A1.533 (10)C15—H15A0.9600
N2—C111.497 (3)C15—H15B0.9600
N2—C141.501 (3)C15—H15C0.9600
N2—C11A1.490 (8)C11A—H11C0.9700
N2—C14A1.510 (8)C11A—H11D0.9700
C1—H1A0.9300C11A—C12A1.516 (9)
C1—C81.364 (3)C12A—H12C0.9700
C2—C31.404 (3)C12A—H12D0.9700
C2—C71.419 (3)C12A—C13A1.515 (9)
C3—H30.9300C13A—H13D0.9600
C3—C41.357 (4)C13A—H13E0.9600
C4—H40.9300C13A—H13F0.9600
C4—C51.384 (3)C14A—H14C0.9700
C5—H50.9300C14A—H14D0.9700
C5—C61.368 (3)C14A—C15A1.525 (11)
C6—C71.396 (3)C15A—H15D0.9600
C7—C81.426 (3)C15A—H15E0.9600
C8—C91.519 (3)C15A—H15F0.9600
C8—C9A1.524 (10)C16—C171.494 (3)
C9—H9A0.9700C17—H17A0.9600
C9—H9B0.9700C17—H17B0.9600
C9—C101.508 (3)C17—H17C0.9600
C10—H10A0.9700C18—C191.494 (3)
C10—H10B0.9700C19—C19i1.298 (4)
C9A—H9AA0.9700C19—H190.9300
C9A—H9AB0.9700C20—C211.492 (2)
C9A—C10A1.491 (10)C21—C21ii1.305 (4)
C10A—H10C0.9700C21—H210.9300
C16—O1—C6119.21 (16)C11—C12—H12B109.6
C18—O4—H4A113.2 (19)C11—C12—C13110.1 (4)
C1—N1—H1131.7 (19)H12A—C12—H12B108.2
C2—N1—H1117.7 (19)C13—C12—H12A109.6
C2—N1—C1109.69 (18)C13—C12—H12B109.6
C10—N2—H2105.7 (15)C12—C13—H13A109.5
C10A—N2—H2108.6 (18)C12—C13—H13B109.5
C11—N2—H2105.9 (15)C12—C13—H13C109.5
C11—N2—C10114.7 (3)H13A—C13—H13B109.5
C11—N2—C14114.0 (4)H13A—C13—H13C109.5
C14—N2—H2106.6 (15)H13B—C13—H13C109.5
C14—N2—C10109.2 (3)N2—C14—H14A108.4
C11A—N2—H2112.0 (16)N2—C14—H14B108.4
C11A—N2—C10A127.9 (15)N2—C14—C15115.6 (3)
C11A—N2—C14A114.3 (14)H14A—C14—H14B107.4
C14A—N2—H297.4 (18)C15—C14—H14A108.4
C14A—N2—C10A90.9 (7)C15—C14—H14B108.4
N1—C1—H1A124.9C14—C15—H15A109.5
C8—C1—N1110.2 (2)C14—C15—H15B109.5
C8—C1—H1A124.9C14—C15—H15C109.5
N1—C2—C3131.9 (2)H15A—C15—H15B109.5
N1—C2—C7106.0 (2)H15A—C15—H15C109.5
C3—C2—C7122.1 (2)H15B—C15—H15C109.5
C2—C3—H3121.0N2—C11A—H11C111.2
C4—C3—C2117.9 (2)N2—C11A—H11D111.2
C4—C3—H3121.0N2—C11A—C12A103.0 (10)
C3—C4—H4119.2H11C—C11A—H11D109.1
C3—C4—C5121.7 (2)C12A—C11A—H11C111.2
C5—C4—H4119.2C12A—C11A—H11D111.2
C4—C5—H5119.8C11A—C12A—H12C111.9
C6—C5—C4120.4 (2)C11A—C12A—H12D111.9
C6—C5—H5119.8H12C—C12A—H12D109.6
C5—C6—O1119.70 (19)C13A—C12A—C11A99.6 (9)
C5—C6—C7121.20 (19)C13A—C12A—H12C111.9
C7—C6—O1118.72 (18)C13A—C12A—H12D111.9
C2—C7—C8108.50 (19)C12A—C13A—H13D109.5
C6—C7—C2116.6 (2)C12A—C13A—H13E109.5
C6—C7—C8134.88 (18)C12A—C13A—H13F109.5
C1—C8—C7105.5 (2)H13D—C13A—H13E109.5
C1—C8—C9130.6 (2)H13D—C13A—H13F109.5
C1—C8—C9A105.2 (12)H13E—C13A—H13F109.5
C7—C8—C9123.84 (18)N2—C14A—H14C106.3
C7—C8—C9A138.6 (9)N2—C14A—H14D106.3
C8—C9—H9A108.9N2—C14A—C15A124.1 (16)
C8—C9—H9B108.9H14C—C14A—H14D106.4
H9A—C9—H9B107.7C15A—C14A—H14C106.3
C10—C9—C8113.5 (2)C15A—C14A—H14D106.3
C10—C9—H9A108.9C14A—C15A—H15D109.5
C10—C9—H9B108.9C14A—C15A—H15E109.5
N2—C10—C9110.48 (19)C14A—C15A—H15F109.5
N2—C10—H10A109.6H15D—C15A—H15E109.5
N2—C10—H10B109.6H15D—C15A—H15F109.5
C9—C10—H10A109.6H15E—C15A—H15F109.5
C9—C10—H10B109.6O1—C16—C17110.6 (2)
H10A—C10—H10B108.1O2—C16—O1122.7 (2)
C8—C9A—H9AA109.5O2—C16—C17126.7 (2)
C8—C9A—H9AB109.5C16—C17—H17A109.5
H9AA—C9A—H9AB108.0C16—C17—H17B109.5
C10A—C9A—C8110.9 (12)C16—C17—H17C109.5
C10A—C9A—H9AA109.5H17A—C17—H17B109.5
C10A—C9A—H9AB109.5H17A—C17—H17C109.5
N2—C10A—H10C109.5H17B—C17—H17C109.5
N2—C10A—H10D109.5O3—C18—O4124.62 (19)
C9A—C10A—N2110.9 (12)O3—C18—C19123.65 (19)
C9A—C10A—H10C109.5O4—C18—C19111.71 (18)
C9A—C10A—H10D109.5C18—C19—H19118.8
H10C—C10A—H10D108.1C19i—C19—C18122.3 (3)
N2—C11—H11A109.2C19i—C19—H19118.8
N2—C11—H11B109.2O5—C20—O6123.40 (16)
N2—C11—C12112.2 (3)O5—C20—C21118.75 (17)
H11A—C11—H11B107.9O6—C20—C21117.85 (16)
C12—C11—H11A109.2C20—C21—H21118.1
C12—C11—H11B109.2C21ii—C21—C20123.8 (2)
C11—C12—H12A109.6C21ii—C21—H21118.1
O1—C6—C7—C2−169.44 (17)C4—C5—C6—C7−1.1 (3)
O1—C6—C7—C88.5 (3)C5—C6—C7—C23.5 (3)
O3—C18—C19—C19i16.7 (4)C5—C6—C7—C8−178.5 (2)
O4—C18—C19—C19i−162.0 (2)C6—O1—C16—O2−2.6 (3)
O5—C20—C21—C21ii−1.5 (4)C6—O1—C16—C17176.42 (19)
O6—C20—C21—C21ii177.7 (2)C6—C7—C8—C1−177.5 (2)
N1—C1—C8—C7−0.2 (3)C6—C7—C8—C94.6 (4)
N1—C1—C8—C9177.5 (2)C6—C7—C8—C9A−40.9 (16)
N1—C1—C8—C9A−152.1 (9)C7—C2—C3—C40.9 (3)
N1—C2—C3—C4179.3 (2)C7—C8—C9—C10−176.3 (2)
N1—C2—C7—C6177.81 (18)C7—C8—C9A—C10A128.1 (16)
N1—C2—C7—C8−0.7 (2)C8—C9—C10—N2165.70 (19)
N2—C11—C12—C13169.6 (5)C8—C9A—C10A—N2−167.0 (16)
N2—C11A—C12A—C13A179.8 (14)C10—N2—C11—C12−175.5 (4)
C1—N1—C2—C3−178.1 (2)C10—N2—C14—C15−75.4 (5)
C1—N1—C2—C70.6 (3)C10A—N2—C11A—C12A−42 (2)
C1—C8—C9—C106.4 (4)C10A—N2—C14A—C15A−173 (3)
C1—C8—C9A—C10A−95 (2)C11—N2—C10—C964.1 (4)
C2—N1—C1—C8−0.2 (3)C11—N2—C14—C1554.3 (6)
C2—C3—C4—C51.7 (3)C14—N2—C10—C9−166.6 (3)
C2—C7—C8—C10.5 (2)C14—N2—C11—C1257.5 (6)
C2—C7—C8—C9−177.3 (2)C11A—N2—C10A—C9A−114 (3)
C2—C7—C8—C9A137.2 (16)C11A—N2—C14A—C15A54 (3)
C3—C2—C7—C6−3.4 (3)C14A—N2—C10A—C9A124 (3)
C3—C2—C7—C8178.10 (19)C14A—N2—C11A—C12A70 (2)
C3—C4—C5—C6−1.7 (3)C16—O1—C6—C594.6 (2)
C4—C5—C6—O1171.77 (19)C16—O1—C6—C7−92.4 (2)
Symmetry codes: (i) −x, −y, −z+2; (ii) −x, −y, −z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4A···O60.89 (1)1.65 (1)2.531 (2)168 (3)
N2—H2···O5iii0.88 (1)1.89 (1)2.757 (2)166 (2)
C9—H9A···O5iii0.972.513.316 (3)141
C10—H10A···O2iv0.972.633.537 (3)156
C9A—H9AB···O5iii0.972.443.24 (2)139
C9A—H9AB···N1v0.972.673.28 (2)121
C12A—H12D···O2iv0.972.533.441 (17)156
Symmetry codes: (iii) x, y−1, z+1; (iv) −x+1, −y−1, −z+2; (v) −x, −y−1, −z+2.
 

Acknowledgements

Financial statements and conflict of inter­est: This study was funded by CaaMTech, Inc. ARC reports an ownership inter­est in CaaMTech, Inc., which owns US and worldwide patent applications, covering new tryptamine compounds, compositions, formulations, novel crystalline forms, and methods of making and using the same.

Funding information

Funding for this research was provided by: National Science Foundation, Directorate for Mathematical and Physical Sciences (grant No. CHE-1429086).

References

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Volume 8| Part 9| September 2023| x230779
https://doi.org/10.1107/S2414314623007794