research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

Bis(4-hy­dr­oxy-N-iso­propyl-N-methyl­trypt­ammo­nium) fumarate: a new crystalline form of miprocin

aCaaMTech, LLC, 58 East Sunset Way, Suite 209, Issaquah, WA 98027, USA, and bUniversity of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747, USA
*Correspondence e-mail: andrew@caam.tech

Edited by M. Zeller, Purdue University, USA (Received 22 February 2020; accepted 2 March 2020; online 10 March 2020)

The title compound, bis­(4-hy­droxy-N-isopropyl-N-methyl­tryptammonium) (4-HO-MiPT) fumarate (systematic name: bis­{[2-(4-hy­droxy-1H-indol-3-yl)eth­yl](meth­yl)propan-2-yl­aza­nium} but-2-enedioate), 2C14H21N2O+·C4H2O42−, has a singly protonated tryptammonium cation and one half of a fumarate dianion in the asymmetric unit. The tryptammonium and fumarate ions are held together in one-dimensional chains by N—H⋯O and O—H⋯O hydrogen bonds. These chains are a combination of R42(20) rings, and C22(15) and C44(30) parallel chains along (110). They are further consolidated by N—H⋯π inter­actions. There are two two-component types of disorder impacting the tryptammonium fragment with a 0.753 (7):0.247 (7) occupancy ratio and one of the fumarate oxygen atoms with a 0.73 (8):0.27 (8) ratio.

1. Chemical context

A wide variety of naturally occurring organisms, including over 200 species of `magic' mushrooms, contain psychoactive tryptamine compounds (Stamets, 1996[Stamets, P. (1996). Psilocybin mushrooms of the world: An identification guide. Berkeley, CA: Ten Speed Press.]). Of these compounds, psilocybin has received the most scientific and commercial attention because of recent studies demonstrating its potential for treating mood disorders including addiction, anxiety, depression and PTSD (Johnson & Griffiths, 2017[Johnson, M. W. & Griffiths, R. R. (2017). Neurotherapeutics 14, 734-740.]; Carhart-Harris & Goodwin, 2017[Carhart-Harris, R. L. & Goodwin, G. M. (2017). Neuropsychopharmacology, 42, 2105-2113.]).

Although psilocybin is currently classified as a schedule I drug, the US Food and Drug Administration recently designated treatment using psilocybin a `breakthrough therapy'. This status has allowed psilocybin to be administered in clinical trials to treat major depressive disorder and treatment-resistant depression (Feltman, 2019[Feltman, R. (2019). Popular Science. https://popsci. com/story/health/psilocybin-magic-mushroom-fda-breakthrough-depression/]). Recent reports also suggest that psychedelic microdosing can improve memory, attention and sociability (Cameron, et al. 2020[Cameron, L. P., Nazarian, A. & Olson, D. E. (2020). J. Psychoactive Drugs, 10 pages, DOI: 10.1080/02791072.2020.1718250.]).

Psilocybin is one of at least ten psychoactive tryptamines present in `magic' mushrooms, with natural psilocybin analogs being identified as recently as 2019 (Lenz et al., 2017[Lenz, C., Wick, J. & Hoffmeister, D. (2017). J. Nat. Prod. 80, 2835-2838.]; Blei et al., 2020[Blei, F., Dörner, S., Fricke, J., Baldeweg, F., Trottmann, F., Komor, A., Meyer, F., Hertweck, C. & Hoffmeister, D. (2020). Chem. Eur. J. 26, 729-734.]). Variations in the three-dimensional structure of these natural analogs (as well as synthetic analogs) correlate with differences in their cellular and clinical pharmacology through their structure–activity relationship (SAR) (Nichols, 2018). Understanding the SAR for psilocybin analogs requires the attainment of accurate information about each compound's 3D structure, best provided through single crystal X-ray diffraction.

Last year, we reported the structure of 4-acet­oxy-N,N-di­methyl ­tryptamine (4-AcO-DMT) fumarate, which is a syn­thetic analogue of psilocybin. The compound crystallized as a one-to-one tryptammonium/hydro­fumarate salt (Chadeayne et al., 2019c[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019c). Psychedelic Science Review. https://psychedelicreview. com/the-crystal-structure-of-4-aco-dmt-fumarate/.]). We later synthesized bis­(4-acet­oxy-N,N-di­methyl­tryprammonium)­fumarate by treating 4-AcO-DMT fumarate with one half equivalent of lead(II) acetate, precipitating half of the fumarate dianions as lead(II) fumarate (Chadeayne, Golen & Manke, 2019a[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019a). Acta Cryst. E75, 900-902.]).

[Scheme 1]

4-Hy­droxy-N-methyl-N-iso­propyl­tryptamine (4-HO-MiPT), aka `miprocin', is a psilocybin analogue. Its synthesis was first reported in 1981 by Repke and co-workers (Repke et al., 1981[Repke, D. B., Ferguson, W. J. & Bates, D. K. (1981). J. Heterocycl. Chem. 18, 175-179.]); its psychedelic effects were later described in collaboration with Alexander Shulgin (Repke et al., 1985[Repke, D. B., Grotjahn, D. B. & Shulgin, A. T. (1985). J. Med. Chem. 28, 892-896.]). Miprocin is reported to produce an experience that is both relaxing, stoning and mildly sedating with a marked physical stimulation that distinguishes it from related substances such as psilocybin mushrooms. In a report last year, we presented the first structure of 4-HO-MiPT (Chadeayne, Pham et al., 2019a[Chadeayne, A. R., Pham, D. N. K., Golen, J. A. & Manke, D. R. (2019a). Acta Cryst. E75, 1316-1320.]), which crystallizes as the hydro­fumarate monohydrate. Herein we report the reaction of this salt with lead(II) acetate to generate the 4-hy­droxy-N-isopropyl-N-methyl­tryptam­in­ium/fumarate compound in a 2:1 ratio. The solid state structure of the new salt is presented here.

2. Structural commentary

The asymmetric unit of bis­(4-hy­droxy-N-isopropyl-N-methyl­trypt­ammo­nium) fumarate contains one tryptammonium cation and one half of a fumarate dianion (Fig. 1[link]). The cation possesses a near planar indole, with mean deviation from planarity of 0.014 Å. The methyl­amino group is turned away from this plane, with a C1—C8—C9—C10 torsion angle of −74.2 (2)°. The N-isopropyl-N-methyl­trypt­ammo­nium group is disordered over two orientations in a 0.753 (7):0.247 (7) ratio, with the two moieties related to each other by a pseudo-mirror operation. In solution, the two conformations are most likely inter­converting into each other by rapid de- and reprotonation. One oxygen atom of the half fumarate anion is also disordered over two positions in a 0.73 (8):0.27 (8) ratio. Half of the fumarate dianion is present in the asymmetric unit, with the other half generated by inversion; it is slightly distorted from planarity with r.m.s. deviations of 0.020 and 0.070 Å for the two components. The carboxyl­ate unit is fairly delocalized, with C—O distances ranging from 1.251 (10) to 1.284 (2) Å.

[Figure 1]
Figure 1
The mol­ecular structure of bis­(4-hy­droxy-N-isopropyl-N-methyl­tryptammonium)­fumarate, showing the atom labeling. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines. Symmetry code: (i) 1 − x, 1 − y, 1 − z.

3. Supra­molecular features

There are N2—H2⋯O2 and N2A—H2A⋯O2 hydrogen bonds between the two configurations of the ammonium cations and one fumarate oxygen. These two different N—H⋯O hydrogen bonds, resulting from the disorder, are also likely to be what produces the fumarate disorder. There is an O1—H1⋯O2 hydrogen bond between the phenol hy­droxy group and one fumarate oxygen atom. Two tryptammonium cations and two fumarate anions are joined together through the N—H⋯O and O—H⋯O hydrogen bonds (Fig. 2[link]), forming rings with graph-set notation R42(20) (Etter et al., 1990[Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256-262.]). The rings are joined together by two parallel chains along (110). These chains have graph-set notation C22(15) and C44(30). The chains and rings are shown in Fig. 3[link]. The ions are further linked through N—H⋯π inter­actions between the indole N–H and the aromatic ring of the indole of another tryptammonium ion (Fig. 2[link]). The hydrogen bonds in the system are outlined in Table 1[link]. The packing of the compound is shown in Fig. 4[link].

Table 1
Hydrogen-bond geometry (Å, °)

Cg2 is the centroid of the C1–C6 ring.

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1⋯O2 0.89 (1) 1.75 (1) 2.618 (2) 165 (2)
N2—H2⋯O2i 0.88 (1) 1.85 (1) 2.730 (5) 175 (3)
N2A—H2A⋯O2i 0.87 (1) 1.89 (4) 2.727 (12) 160 (11)
N1—H1ACg2ii 0.87 (1) 2.78 (2) 3.552 (3) 148 (2)
Symmetry codes: (i) [-x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]; (ii) [-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{3\over 2}}].
[Figure 2]
Figure 2
The hydrogen bonding of the tryptammonium cation in the structure of the title compound (Table 1[link]), with hydrogen bonds shown as dashed lines. There is also an N—H⋯π inter­action shown. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms not involved in hydrogen bonds are omitted for clarity. Symmetry codes: (i) [{1\over 2}] − x, [{3\over 2}] − y, 1 − z, (ii) [{1\over 2}] − x, −[{1\over 2}] + y, [{3\over 2}] − z.
[Figure 3]
Figure 3
The hydrogen-bonding network along (110), which consists of R42(20) rings that are joined together by two parallel C22(15) and C44(30) chains. The three components described in graph-set notation and the combined chain are 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.
[Figure 4]
Figure 4
The crystal packing of the title compound, viewed along the a axis. The N—H⋯O and O—H⋯O hydrogen bonds (Table 1[link]) are shown as dashed lines. Hydrogen atoms not involved in hydrogen bonding are omitted for clarity.

4. Database survey

The structure of a number of neutral tryptamines have been reported, including psilocin (Petcher & Weber, 1974[Petcher, T. J. & Weber, H. P. (1974). J. Chem. Soc. Perkin Trans. 2, pp. 946-948.]), psilocybin (Weber & Petcher, 1974[Weber, H. P. & Petcher, T. J. (1974). J. Chem. Soc. Perkin Trans. 2, pp. 942-946.]), bufotenine (Falkenberg, 1972b[Falkenberg, G. (1972b). Acta Cryst. B28, 3219-3228.]), DMT (Falkenberg, 1972a[Falkenberg, G. (1972a). Acta Cryst. B28, 3075-3083.]) and MPT (Chadeayne, Golen & Manke, 2019b[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019b). IUCrData, 4, x190962.]). A series of one-to-one tryptammonium hydro­fumarate salts have been structurally characterized, including psilacetin (Chadeayne et al., 2019c[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019c). Psychedelic Science Review. https://psychedelicreview. com/the-crystal-structure-of-4-aco-dmt-fumarate/.]), miprocin and MiPT (Chadeayne, Pham et al., 2019a[Chadeayne, A. R., Pham, D. N. K., Golen, J. A. & Manke, D. R. (2019a). Acta Cryst. E75, 1316-1320.]). As discussed above, the two-to-one tryptammonium/fumarate salt of 4-AcO-DMT was previously prepared and its structure reported (Chadeayne, Golen & Manke, 2019a[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019a). Acta Cryst. E75, 900-902.]). The only other reported two-to-one tryptammonium fumarate salt was that of 4-HO-DPT, or procin (Chadeayne, Pham et al., 2019b[Chadeayne, A. R., Pham, D. N. K., Golen, J. A. & Manke, D. R. (2019b). IUCrData, 4, x191469.]). The metrical parameters of the tryptammonium cations of 4-HO-MiPT are comparable to those observed for the other reported tryptamine structures.

5. Synthesis and crystallization

61.2 mg of 4-HO-MiPT fumarate were dissolved in 10 mL of deionized water. 29.3 mg of lead(II) acetate was dissolved in 2 mL of deionized water and then added to the tryptamine solution. After sonication, a white precipitate formed. The powder was removed via vacuum filtration. The solvent was removed from the resulting solution in vacuo to yield a sticky powder. The powder was recrystallized from methanol to yield single crystals suitable for X-ray diffraction.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. Hydrogen atoms H1, H1A, H2 and H2A were found from a difference- Fourier map and were refined isotropically, using DFIX restraints with N—H distances of 0.87 (1) Å and an O—H distance of 0.88 (1) Å. Isotropic displacement parameters were set to 1.2Ueq of the parent indolic nitro­gen atom and 1.5Ueq of the parent oxygen atom and the parent ammonium nitro­gen atoms. All other hydrogen atoms were placed in calculated positions with appropriate carbon–hydrogen bond lengths: (sp2) 0.95 Å, (CH3) 0.98 Å, (CH2) 0.99 Å and (CH) 1.00 Å. Isotropic displacement parameters were set to 1.2Ueq(C) for sp2, CH and CH2 parent carbon atoms and 1.5Ueq(C-meth­yl). Atoms N2 and C11–C14 were modeled as being disordered over two sets of sites [0.753 (7):0.247 (7)] and refined with SADI (0.03) restraints on C—C(meth­yl) and N—C(meth­yl) bonds to maintain consistent bond lengths in the disorder. Oxygen atom O3 was also modeled as disordered over two sites [0.73 (8):0.27 (8)].

Table 2
Experimental details

Crystal data
Chemical formula C14H21N2O+·C2HO2
Mr 290.35
Crystal system, space group Monoclinic, C2/c
Temperature (K) 200
a, b, c (Å) 19.770 (13), 9.477 (6), 17.620 (12)
β (°) 105.78 (2)
V3) 3177 (4)
Z 8
Radiation type Mo Kα
μ (mm−1) 0.08
Crystal size (mm) 0.25 × 0.2 × 0.1
 
Data collection
Diffractometer Bruker D8 Venture CMOS
Absorption correction Multi-scan (SADABS; Bruker, 2018[Bruker (2018). APEX3, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.692, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections 39417, 2890, 2007
Rint 0.086
(sin θ/λ)max−1) 0.606
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.047, 0.105, 1.06
No. of reflections 2890
No. of parameters 265
No. of restraints 11
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.15, −0.13
Computer programs: APEX3 and SAINT (Bruker, 2018[Bruker (2018). APEX3, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2014 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2018 (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.]).

Supporting information


Computing details top

Data collection: APEX3 (Bruker, 2018); cell refinement: SAINT (Bruker, 2018); data reduction: SAINT (Bruker, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

Bis{[2-(4-hydroxy-1H-indol-3-yl)ethyl](methyl)propan-2-ylazanium} but-2-enedioate top
Crystal data top
C14H21N2O+·C2HO2F(000) = 1248
Mr = 290.35Dx = 1.214 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
a = 19.770 (13) ÅCell parameters from 5659 reflections
b = 9.477 (6) Åθ = 2.6–23.3°
c = 17.620 (12) ŵ = 0.08 mm1
β = 105.78 (2)°T = 200 K
V = 3177 (4) Å3Block, colourless
Z = 80.25 × 0.2 × 0.1 mm
Data collection top
Bruker D8 Venture CMOS
diffractometer
2007 reflections with I > 2σ(I)
φ and ω scansRint = 0.086
Absorption correction: multi-scan
(SADABS; Bruker, 2018)
θmax = 25.5°, θmin = 2.6°
Tmin = 0.692, Tmax = 0.745h = 2323
39417 measured reflectionsk = 1111
2890 independent reflectionsl = 2121
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.047H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.105 w = 1/[σ2(Fo2) + (0.0307P)2 + 2.6574P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
2890 reflectionsΔρmax = 0.15 e Å3
265 parametersΔρmin = 0.13 e Å3
11 restraintsExtinction correction: SHELXL2018 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: iterativeExtinction coefficient: 0.0036 (5)
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)
O10.31856 (7)0.49585 (15)0.58406 (9)0.0493 (4)
H10.3549 (9)0.553 (2)0.5887 (14)0.074*
N10.21977 (11)0.1682 (2)0.71648 (12)0.0605 (5)
H1A0.2128 (12)0.107 (2)0.7503 (11)0.073*
C10.27162 (10)0.33085 (19)0.65757 (11)0.0381 (5)
C20.32760 (11)0.42144 (19)0.65257 (12)0.0400 (5)
C30.38761 (11)0.4290 (2)0.71573 (13)0.0505 (6)
H30.4250860.4895620.7126910.061*
C40.39340 (13)0.3476 (3)0.78447 (14)0.0609 (6)
H40.4348900.3547220.8268790.073*
C50.34054 (14)0.2583 (3)0.79158 (14)0.0620 (7)
H50.3449460.2038620.8379660.074*
C60.27957 (12)0.2504 (2)0.72753 (13)0.0487 (6)
C70.17506 (12)0.1943 (2)0.64280 (13)0.0522 (6)
H70.1306410.1505380.6221000.063*
C80.20396 (10)0.29280 (19)0.60364 (12)0.0400 (5)
C90.17292 (11)0.33949 (19)0.51916 (12)0.0431 (5)
H9A0.1333460.2761430.4940620.052*
H9B0.2090800.3291630.4901730.052*
C100.14642 (10)0.49194 (19)0.51102 (11)0.0392 (5)
H10A0.1120790.5038340.5422690.047*0.753 (7)
H10B0.1864800.5559140.5333430.047*0.753 (7)
H10C0.0984380.4945560.5180710.047*0.247 (7)
H10D0.1772450.5497750.5533150.047*0.247 (7)
N20.1120 (2)0.5345 (4)0.4263 (3)0.0424 (10)0.753 (7)
H20.1020 (16)0.6251 (14)0.427 (2)0.064*0.753 (7)
C110.16090 (17)0.5281 (3)0.37193 (17)0.0460 (11)0.753 (7)
H110.1742450.4274480.3668980.055*0.753 (7)
C120.1208 (6)0.5835 (11)0.2891 (5)0.075 (2)0.753 (7)
H12A0.0817240.5196860.2655210.113*0.753 (7)
H12B0.1528960.5876410.2554950.113*0.753 (7)
H12C0.1024180.6780460.2940750.113*0.753 (7)
C130.2280 (5)0.6136 (11)0.4063 (5)0.0550 (16)0.753 (7)
H13A0.2548480.5705690.4558890.082*0.753 (7)
H13B0.2154250.7106100.4162310.082*0.753 (7)
H13C0.2565260.6144810.3687170.082*0.753 (7)
C140.0444 (4)0.4557 (8)0.3919 (4)0.0602 (16)0.753 (7)
H14A0.0122690.5150340.3526070.090*0.753 (7)
H14B0.0226430.4320960.4340910.090*0.753 (7)
H14C0.0543370.3688330.3668170.090*0.753 (7)
N2A0.1450 (7)0.5560 (14)0.4311 (9)0.050 (3)0.247 (7)
H2A0.134 (5)0.643 (4)0.439 (7)0.075*0.247 (7)
C11A0.1027 (5)0.4723 (9)0.3612 (6)0.056 (4)0.247 (7)
H11A0.1294900.3831190.3605570.067*0.247 (7)
C12A0.1043 (18)0.553 (3)0.2865 (15)0.072 (9)0.247 (7)
H12D0.1520270.5877360.2916180.108*0.247 (7)
H12E0.0717260.6328580.2790340.108*0.247 (7)
H12F0.0902420.4897240.2408400.108*0.247 (7)
C13A0.0317 (13)0.428 (3)0.3716 (17)0.083 (7)0.247 (7)
H13D0.0388190.3593790.4147640.124*0.247 (7)
H13E0.0034800.3844610.3226710.124*0.247 (7)
H13F0.0070610.5107260.3839460.124*0.247 (7)
C14A0.2162 (13)0.601 (3)0.4231 (16)0.048 (5)0.247 (7)
H14D0.2102870.6772960.3845730.072*0.247 (7)
H14E0.2389060.5200500.4051640.072*0.247 (7)
H14F0.2454520.6330160.4742990.072*0.247 (7)
O20.41362 (7)0.68230 (14)0.57453 (9)0.0518 (4)
C150.45985 (11)0.6662 (2)0.53625 (14)0.0489 (5)
C160.47710 (10)0.5170 (2)0.51944 (13)0.0438 (5)
H160.4535120.4427830.5380170.053*
O30.4846 (16)0.7662 (12)0.5058 (18)0.079 (4)0.73 (8)
O3A0.5040 (17)0.762 (4)0.537 (4)0.066 (7)0.27 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0463 (9)0.0440 (8)0.0593 (9)0.0065 (7)0.0175 (7)0.0114 (7)
N10.0821 (14)0.0515 (12)0.0562 (13)0.0066 (11)0.0332 (11)0.0146 (10)
C10.0498 (12)0.0287 (10)0.0412 (11)0.0039 (9)0.0215 (10)0.0007 (8)
C20.0464 (12)0.0298 (10)0.0474 (12)0.0064 (9)0.0189 (10)0.0015 (9)
C30.0466 (13)0.0467 (12)0.0581 (14)0.0043 (10)0.0145 (12)0.0041 (11)
C40.0633 (15)0.0632 (15)0.0520 (14)0.0116 (13)0.0085 (12)0.0056 (12)
C50.0827 (18)0.0618 (15)0.0435 (14)0.0132 (14)0.0206 (14)0.0069 (11)
C60.0628 (15)0.0419 (12)0.0475 (13)0.0043 (11)0.0251 (12)0.0032 (10)
C70.0583 (14)0.0436 (12)0.0600 (15)0.0069 (10)0.0253 (12)0.0032 (11)
C80.0485 (12)0.0290 (10)0.0485 (12)0.0010 (8)0.0234 (10)0.0018 (9)
C90.0504 (12)0.0305 (10)0.0503 (12)0.0006 (9)0.0168 (10)0.0035 (9)
C100.0436 (11)0.0336 (10)0.0454 (12)0.0016 (9)0.0204 (10)0.0011 (9)
N20.048 (2)0.0347 (16)0.0467 (19)0.0054 (18)0.016 (2)0.0011 (13)
C110.063 (3)0.0365 (16)0.0449 (19)0.0035 (15)0.0246 (17)0.0003 (13)
C120.102 (4)0.074 (6)0.049 (3)0.009 (4)0.019 (3)0.009 (3)
C130.051 (4)0.063 (3)0.059 (3)0.001 (3)0.028 (2)0.010 (3)
C140.056 (4)0.044 (3)0.074 (3)0.016 (2)0.007 (3)0.003 (3)
N2A0.060 (8)0.034 (6)0.056 (6)0.022 (6)0.017 (7)0.001 (5)
C11A0.059 (8)0.034 (5)0.064 (7)0.004 (5)0.000 (5)0.007 (5)
C12A0.13 (2)0.032 (8)0.054 (10)0.029 (12)0.032 (12)0.011 (6)
C13A0.048 (10)0.061 (11)0.130 (18)0.024 (7)0.007 (11)0.035 (10)
C14A0.049 (9)0.039 (7)0.074 (12)0.011 (6)0.046 (7)0.010 (7)
O20.0507 (9)0.0341 (7)0.0808 (11)0.0017 (6)0.0353 (8)0.0008 (7)
C150.0470 (12)0.0326 (11)0.0739 (16)0.0036 (10)0.0278 (12)0.0051 (11)
C160.0402 (11)0.0306 (10)0.0651 (14)0.0004 (9)0.0221 (10)0.0069 (9)
O30.100 (8)0.0310 (18)0.137 (9)0.008 (3)0.083 (7)0.017 (4)
O3A0.057 (10)0.031 (6)0.124 (19)0.012 (6)0.048 (11)0.001 (9)
Geometric parameters (Å, º) top
O1—H10.885 (10)C11—C131.531 (10)
O1—C21.367 (2)C12—H12A0.9800
N1—H1A0.870 (10)C12—H12B0.9800
N1—C61.385 (3)C12—H12C0.9800
N1—C71.380 (3)C13—H13A0.9800
C1—C21.422 (3)C13—H13B0.9800
C1—C61.421 (3)C13—H13C0.9800
C1—C81.460 (3)C14—H14A0.9800
C2—C31.390 (3)C14—H14B0.9800
C3—H30.9500C14—H14C0.9800
C3—C41.414 (3)N2A—H2A0.874 (11)
C4—H40.9500N2A—C11A1.511 (18)
C4—C51.377 (3)N2A—C14A1.51 (2)
C5—H50.9500C11A—H11A1.0000
C5—C61.412 (3)C11A—C12A1.53 (2)
C7—H70.9500C11A—C13A1.52 (2)
C7—C81.374 (3)C12A—H12D0.9800
C8—C91.514 (3)C12A—H12E0.9800
C9—H9A0.9900C12A—H12F0.9800
C9—H9B0.9900C13A—H13D0.9800
C9—C101.530 (3)C13A—H13E0.9800
C10—H10A0.9900C13A—H13F0.9800
C10—H10B0.9900C14A—H14D0.9800
C10—H10C0.9900C14A—H14E0.9800
C10—H10D0.9900C14A—H14F0.9800
C10—N21.518 (5)O2—C151.284 (2)
C10—N2A1.527 (15)C15—C161.503 (3)
N2—H20.882 (10)C15—O31.251 (10)
N2—C111.536 (5)C15—O3A1.26 (3)
N2—C141.506 (7)C16—C16i1.315 (4)
C11—H111.0000C16—H160.9500
C11—C121.550 (9)
C2—O1—H1109.0 (16)C13—C11—C12111.0 (5)
C6—N1—H1A124.6 (17)C11—C12—H12A109.5
C7—N1—H1A125.8 (17)C11—C12—H12B109.5
C7—N1—C6109.58 (18)C11—C12—H12C109.5
C2—C1—C8134.38 (18)H12A—C12—H12B109.5
C6—C1—C2118.24 (19)H12A—C12—H12C109.5
C6—C1—C8107.32 (18)H12B—C12—H12C109.5
O1—C2—C1116.68 (18)C11—C13—H13A109.5
O1—C2—C3123.93 (19)C11—C13—H13B109.5
C3—C2—C1119.38 (19)C11—C13—H13C109.5
C2—C3—H3119.7H13A—C13—H13B109.5
C2—C3—C4120.7 (2)H13A—C13—H13C109.5
C4—C3—H3119.7H13B—C13—H13C109.5
C3—C4—H4119.1N2—C14—H14A109.5
C5—C4—C3121.8 (2)N2—C14—H14B109.5
C5—C4—H4119.1N2—C14—H14C109.5
C4—C5—H5121.2H14A—C14—H14B109.5
C4—C5—C6117.6 (2)H14A—C14—H14C109.5
C6—C5—H5121.2H14B—C14—H14C109.5
N1—C6—C1106.9 (2)C10—N2A—H2A100 (8)
N1—C6—C5130.8 (2)C11A—N2A—C10114.2 (10)
C5—C6—C1122.3 (2)C11A—N2A—H2A122 (8)
N1—C7—H7124.8C11A—N2A—C14A113.2 (16)
C8—C7—N1110.3 (2)C14A—N2A—C10114.4 (13)
C8—C7—H7124.8C14A—N2A—H2A92 (7)
C1—C8—C9128.51 (17)N2A—C11A—H11A106.0
C7—C8—C1105.86 (18)N2A—C11A—C12A107.6 (15)
C7—C8—C9125.42 (19)N2A—C11A—C13A111.8 (12)
C8—C9—H9A108.8C12A—C11A—H11A106.0
C8—C9—H9B108.8C13A—C11A—H11A106.0
C8—C9—C10113.90 (16)C13A—C11A—C12A118.5 (19)
H9A—C9—H9B107.7C11A—C12A—H12D109.5
C10—C9—H9A108.8C11A—C12A—H12E109.5
C10—C9—H9B108.8C11A—C12A—H12F109.5
C9—C10—H10A108.9H12D—C12A—H12E109.5
C9—C10—H10B108.9H12D—C12A—H12F109.5
C9—C10—H10C109.1H12E—C12A—H12F109.5
C9—C10—H10D109.1C11A—C13A—H13D109.5
H10A—C10—H10B107.8C11A—C13A—H13E109.5
H10C—C10—H10D107.8C11A—C13A—H13F109.5
N2—C10—C9113.2 (2)H13D—C13A—H13E109.5
N2—C10—H10A108.9H13D—C13A—H13F109.5
N2—C10—H10B108.9H13E—C13A—H13F109.5
N2A—C10—C9112.5 (5)N2A—C14A—H14D109.5
N2A—C10—H10C109.1N2A—C14A—H14E109.5
N2A—C10—H10D109.1N2A—C14A—H14F109.5
C10—N2—H2106 (2)H14D—C14A—H14E109.5
C10—N2—C11114.3 (3)H14D—C14A—H14F109.5
C11—N2—H2104 (2)H14E—C14A—H14F109.5
C14—N2—C10112.0 (4)O2—C15—C16116.58 (17)
C14—N2—H2108 (2)O3—C15—O2123.5 (5)
C14—N2—C11111.7 (4)O3—C15—C16119.5 (5)
N2—C11—H11108.6O3A—C15—O2120.2 (17)
N2—C11—C12109.0 (5)O3A—C15—C16119.1 (14)
C12—C11—H11108.6C15—C16—H16118.0
C13—C11—N2110.9 (4)C16i—C16—C15123.9 (2)
C13—C11—H11108.6C16i—C16—H16118.0
O1—C2—C3—C4179.34 (19)C8—C1—C2—O12.2 (3)
N1—C7—C8—C10.3 (2)C8—C1—C2—C3177.32 (19)
N1—C7—C8—C9174.91 (18)C8—C1—C6—N10.1 (2)
C1—C2—C3—C40.1 (3)C8—C1—C6—C5178.10 (19)
C1—C8—C9—C1074.2 (2)C8—C9—C10—N2176.9 (2)
C2—C1—C6—N1177.84 (17)C8—C9—C10—N2A155.6 (6)
C2—C1—C6—C50.4 (3)C9—C10—N2—C1161.5 (3)
C2—C1—C8—C7177.5 (2)C9—C10—N2—C1466.9 (5)
C2—C1—C8—C92.4 (3)C9—C10—N2A—C11A55.6 (9)
C2—C3—C4—C50.1 (3)C9—C10—N2A—C14A77.0 (14)
C3—C4—C5—C60.1 (3)C10—N2—C11—C12176.2 (5)
C4—C5—C6—N1177.6 (2)C10—N2—C11—C1353.7 (5)
C4—C5—C6—C10.1 (3)C10—N2A—C11A—C12A178.0 (14)
C6—N1—C7—C80.3 (3)C10—N2A—C11A—C13A46.2 (17)
C6—C1—C2—O1179.16 (17)C14—N2—C11—C1255.2 (6)
C6—C1—C2—C30.4 (3)C14—N2—C11—C13177.7 (6)
C6—C1—C8—C70.3 (2)C14A—N2A—C11A—C12A49 (2)
C6—C1—C8—C9174.77 (18)C14A—N2A—C11A—C13A179.3 (19)
C7—N1—C6—C10.1 (2)O2—C15—C16—C16i179.6 (3)
C7—N1—C6—C5178.1 (2)O3—C15—C16—C16i7 (2)
C7—C8—C9—C10111.7 (2)O3A—C15—C16—C16i23 (4)
Symmetry code: (i) x+1, y+1, z+1.
Hydrogen-bond geometry (Å, º) top
Cg2 is the centroid of the C1–C6 ring.
D—H···AD—HH···AD···AD—H···A
O1—H1···O20.89 (1)1.75 (1)2.618 (2)165 (2)
N2—H2···O2ii0.88 (1)1.85 (1)2.730 (5)175 (3)
N2A—H2A···O2ii0.87 (1)1.89 (4)2.727 (12)160 (11)
N1—H1A···Cg2iii0.87 (1)2.78 (2)3.552 (3)148 (2)
Symmetry codes: (ii) x+1/2, y+3/2, z+1; (iii) x+1/2, y1/2, z+3/2.
 

Acknowledgements

We would like to thank Jerry Jasinski for useful advise in analyzing the supra­molecular features. 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.

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