N-Methyl-N-propyl­tryptamine (MPT)

Chadeayne, A.R.; Golen, J.A.; Manke, D.R.

doi:10.1107/S2414314619009623

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 4| Part 7| July 2019| x190962

https://doi.org/10.1107/S2414314619009623

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N-Methyl-N-propyltryptamine (MPT)

Andrew R. Chadeayne,^a ^* James A. Golen ^b and David R. Manke ^b

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

Edited by I. Brito, University of Antofagasta, Chile (Received 24 June 2019; accepted 4 July 2019; online 9 July 2019)

The title compound {systematic name: [2-(1H-indol-3-yl)ethyl](methyl)propylamine}, C₁₄H₂₀N₂, has a single molecule in the asymmetric unit. The molecules in the unit cell are held together in infinite one-dimensional chains along [010] through N—H⋯N hydrogen bonds between indole H atoms and trialkylamine N atoms.

Keywords: crystal structure; tryptamines; indoles; hydrogen bonding.

CCDC reference: 1938495

Structure description

N-Methyl-N-propyltryptamine (MPT) is a structural analog of N,N-dimethyltryptamine (DMT), which is a well known `psychedelic' molecule found in a variety of naturally occurring organisms, including plants, animals, and funghi, including mushrooms. In humans, DMT is the only known endogenous mammalian N,N-dimethylated trace amine (Fontanilla et al., 2009 ). Naturally occurring tryptamines (e.g. DMT, psilocybin, 5-methoxy-N,N-dimethyltryptamine) and their synthetic derivatives (e.g. psilacetin, MPT) have garnered considerable attention of late due to new evidence demonstrating their efficacy in treating mood (e.g. anxiety and depression) and post traumatic stress disorders (PTSDs) (Aixalà et al., 2018 ; Cameron et al., 2019 ).

Psilocybin, isolated from the so-called `magic' mushrooms, is perhaps the best known prodrug of the serotonin 2a agonist psilocin (Nichols, 2016 ). Recent studies indicate that psilocin (and its prodrugs like psilocybin and psilacetin) could provide effective treatment for mood disorders, end-of-life anxiety, addiction, and PTSD (Carhart-Harris et al., 2016 ; Johnson & Griffiths, 2017 ). However, the long duration of action of psilocin and its prodrugs can result in practical challenges for both patients and clinicians (Passie et al., 2002 ). Accordingly, the mental health industry would benefit from exploring alternative tryptamine treatment options that provide similar therapeutic benefits while having a shorter duration of action.

While the synthesis of DMT was first reported in 1931 (Manske, 1931 ), the first literature report of MPT appeared in 2005 (Brandt et al., 2005 ) and it has not undergone significant study. In the solid-state structure of MPT, there is a single molecule in the asymmetric unit, with an indole group that demonstrates a mean deviation from planarity of 0.015 Å (Fig. 1). The metrical parameters are consistent with the previously reported structure of DMT (Falkenberg, 1972 ) and other dialkyltryptamines (Chadeayne et al., 2019a ,b ; Petcher & Weber, 1974 ; Weber & Petcher, 1974 ). The tryptamine molecules are held together in an infinite one-dimensional chain along [010] through N—H⋯N hydrogen bonds connecting the indole N atom to the amine N atom (Table 1, Fig. 2). In the structure of DMT, there are similar hydrogen bonds, but they hold molecules together as dimers rather than in a chain. There are no π–π interactions observed in the structure.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N2ⁱ	0.920 (17)	1.990 (17)	2.9097 (15)	179.8 (16)
Symmetry code: (i) $[-x+{\script{1\over 2}}, y+{\script{1\over 2}}, z]$ .

Figure 1
The molecular structure of the title compound, showing the atomic labelling. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
The crystal packing of the title compound, viewed along the c axis. The N—H⋯N hydrogen bonds are shown as dashed lines. Displacement ellipsoids are drawn at the 50% probability level. H atoms not involved in hydrogen bonding have been omitted for clarity.

Synthesis and crystallization

Single crystals of MPT suitable for X-ray analysis were obtained by the slow evaporation of a methylene chloride solution of a commercial sample of N-methyl-N-propyltryptamine (The Indole Shop).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₄H₂₀N₂
M_r	216.32
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	200
a, b, c (Å)	13.5715 (11), 12.4352 (10), 15.1627 (12)
V (Å³)	2558.9 (4)
Z	8
Radiation type	Mo Kα
μ (mm⁻¹)	0.07
Crystal size (mm)	0.28 × 0.20 × 0.13

Data collection
Diffractometer	Bruker D8 Venture CMOS
Absorption correction	Multi-scan (SADABS; Bruker, 2016 )
T_min, T_max	0.713, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections	47431, 2350, 1942
R_int	0.048
(sin θ/λ)_max (Å⁻¹)	0.604

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.095, 1.05
No. of reflections	2350
No. of parameters	152
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.17, −0.16
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT2014 (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), publCIF (Westrip, 2010 ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1938495

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314619009623/bx4015sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314619009623/bx4015Isup2.hkl

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a) and publCIF (Westrip, 2010); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

[2-(1H-Indol-3-yl)ethyl](methyl)propylamine top

Crystal data top

C₁₄H₂₀N₂	D_x = 1.123 Mg m⁻³
M_r = 216.32	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 9106 reflections
a = 13.5715 (11) Å	θ = 3.0–25.3°
b = 12.4352 (10) Å	µ = 0.07 mm⁻¹
c = 15.1627 (12) Å	T = 200 K
V = 2558.9 (4) Å³	Block, colourless
Z = 8	0.28 × 0.20 × 0.13 mm
F(000) = 944

Data collection top

Bruker D8 Venture CMOS diffractometer	1942 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.048
Absorption correction: multi-scan (SADABS; Bruker, 2016)	θ_max = 25.4°, θ_min = 3.0°
T_min = 0.713, T_max = 0.745	h = −16→16
47431 measured reflections	k = −14→15
2350 independent reflections	l = −18→18

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.036	w = 1/[σ²(F_o²) + (0.040P)² + 0.843P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.095	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.17 e Å⁻³
2350 reflections	Δρ_min = −0.16 e Å⁻³
152 parameters	Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0279 (16)

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

	x	y	z	U_iso*/U_eq
N1	0.15123 (8)	0.54678 (9)	0.71757 (7)	0.0342 (3)
N2	0.47825 (7)	0.22356 (7)	0.76631 (7)	0.0281 (3)
C1	0.20625 (9)	0.48945 (10)	0.77718 (8)	0.0329 (3)
H1A	0.2086	0.5040	0.8387	0.040*
C2	0.16536 (9)	0.50319 (10)	0.63560 (8)	0.0299 (3)
C3	0.12410 (10)	0.53092 (11)	0.55460 (9)	0.0380 (3)
H3	0.0802	0.5901	0.5494	0.046*
C4	0.14904 (10)	0.46983 (12)	0.48231 (9)	0.0438 (4)
H4	0.1221	0.4873	0.4263	0.053*
C7	0.23153 (8)	0.41566 (9)	0.64465 (8)	0.0291 (3)
C5	0.21333 (10)	0.38242 (12)	0.48980 (9)	0.0427 (4)
H5	0.2288	0.3413	0.4389	0.051*
C6	0.25456 (10)	0.35491 (11)	0.56941 (9)	0.0368 (3)
H6	0.2982	0.2954	0.5735	0.044*
C8	0.25697 (9)	0.40901 (9)	0.73654 (8)	0.0299 (3)
C9	0.32024 (9)	0.32514 (10)	0.77938 (9)	0.0347 (3)
H9A	0.2902	0.2536	0.7696	0.042*
H9B	0.3217	0.3382	0.8438	0.042*
C10	0.42572 (9)	0.32375 (10)	0.74460 (9)	0.0334 (3)
H10A	0.4245	0.3328	0.6797	0.040*
H10B	0.4622	0.3854	0.7699	0.040*
C11	0.50645 (10)	0.22182 (10)	0.85999 (8)	0.0341 (3)
H11A	0.4465	0.2323	0.8962	0.041*
H11B	0.5511	0.2832	0.8716	0.041*
C12	0.55691 (12)	0.11938 (12)	0.88919 (10)	0.0473 (4)
H12A	0.6211	0.1130	0.8585	0.057*
H12B	0.5159	0.0570	0.8719	0.057*
C13	0.57384 (14)	0.11646 (13)	0.98776 (10)	0.0574 (4)
H13A	0.6089	0.0503	1.0034	0.086*
H13B	0.5103	0.1184	1.0183	0.086*
H13C	0.6133	0.1789	1.0054	0.086*
C14	0.56449 (10)	0.21237 (11)	0.70873 (9)	0.0402 (3)
H14A	0.5432	0.2125	0.6470	0.060*
H14B	0.5982	0.1446	0.7219	0.060*
H14C	0.6097	0.2726	0.7189	0.060*
H1	0.1103 (12)	0.6027 (13)	0.7328 (10)	0.055 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0332 (6)	0.0297 (6)	0.0396 (6)	0.0077 (5)	−0.0033 (5)	−0.0054 (5)
N2	0.0232 (5)	0.0262 (5)	0.0350 (6)	−0.0004 (4)	−0.0003 (4)	−0.0002 (4)
C1	0.0321 (6)	0.0317 (7)	0.0350 (7)	0.0017 (5)	−0.0026 (5)	−0.0024 (5)
C2	0.0248 (6)	0.0282 (6)	0.0365 (7)	−0.0018 (5)	0.0000 (5)	−0.0019 (5)
C3	0.0322 (7)	0.0386 (7)	0.0434 (8)	0.0002 (6)	−0.0045 (6)	0.0023 (6)
C4	0.0412 (8)	0.0546 (9)	0.0356 (8)	−0.0068 (7)	−0.0034 (6)	0.0001 (6)
C7	0.0231 (6)	0.0255 (6)	0.0386 (7)	−0.0031 (5)	0.0019 (5)	−0.0019 (5)
C5	0.0422 (8)	0.0479 (8)	0.0380 (8)	−0.0059 (6)	0.0052 (6)	−0.0103 (6)
C6	0.0320 (7)	0.0335 (7)	0.0448 (8)	−0.0010 (5)	0.0055 (6)	−0.0074 (6)
C8	0.0252 (6)	0.0263 (6)	0.0383 (7)	−0.0011 (5)	0.0005 (5)	0.0000 (5)
C9	0.0298 (7)	0.0302 (7)	0.0442 (8)	0.0033 (5)	0.0023 (6)	0.0047 (5)
C10	0.0273 (6)	0.0286 (6)	0.0441 (7)	−0.0015 (5)	−0.0006 (5)	0.0065 (5)
C11	0.0339 (7)	0.0307 (7)	0.0377 (7)	−0.0007 (5)	−0.0048 (5)	−0.0025 (5)
C12	0.0545 (9)	0.0413 (8)	0.0462 (8)	0.0095 (7)	−0.0089 (7)	0.0019 (6)
C13	0.0701 (11)	0.0508 (9)	0.0514 (9)	−0.0043 (8)	−0.0200 (8)	0.0090 (7)
C14	0.0288 (7)	0.0439 (8)	0.0478 (8)	0.0014 (6)	0.0060 (6)	0.0007 (6)

Geometric parameters (Å, º) top

N1—C1	1.3722 (16)	C8—C9	1.4991 (17)
N1—C2	1.3695 (16)	C9—H9A	0.9900
N1—H1	0.920 (17)	C9—H9B	0.9900
N2—C10	1.4727 (15)	C9—C10	1.5257 (17)
N2—C11	1.4712 (15)	C10—H10A	0.9900
N2—C14	1.4668 (16)	C10—H10B	0.9900
C1—H1A	0.9500	C11—H11A	0.9900
C1—C8	1.3618 (17)	C11—H11B	0.9900
C2—C3	1.3932 (18)	C11—C12	1.5126 (18)
C2—C7	1.4177 (17)	C12—H12A	0.9900
C3—H3	0.9500	C12—H12B	0.9900
C3—C4	1.3759 (19)	C12—C13	1.513 (2)
C4—H4	0.9500	C13—H13A	0.9800
C4—C5	1.398 (2)	C13—H13B	0.9800
C7—C6	1.4035 (17)	C13—H13C	0.9800
C7—C8	1.4377 (18)	C14—H14A	0.9800
C5—H5	0.9500	C14—H14B	0.9800
C5—C6	1.374 (2)	C14—H14C	0.9800
C6—H6	0.9500

C1—N1—H1	123.8 (10)	H9A—C9—H9B	107.7
C2—N1—C1	108.42 (10)	C10—C9—H9A	108.9
C2—N1—H1	127.7 (10)	C10—C9—H9B	108.9
C11—N2—C10	110.74 (10)	N2—C10—C9	112.74 (10)
C14—N2—C10	109.48 (10)	N2—C10—H10A	109.0
C14—N2—C11	111.45 (10)	N2—C10—H10B	109.0
N1—C1—H1A	124.5	C9—C10—H10A	109.0
C8—C1—N1	111.01 (11)	C9—C10—H10B	109.0
C8—C1—H1A	124.5	H10A—C10—H10B	107.8
N1—C2—C3	130.23 (12)	N2—C11—H11A	108.7
N1—C2—C7	107.74 (11)	N2—C11—H11B	108.7
C3—C2—C7	122.01 (12)	N2—C11—C12	114.38 (10)
C2—C3—H3	121.1	H11A—C11—H11B	107.6
C4—C3—C2	117.83 (13)	C12—C11—H11A	108.7
C4—C3—H3	121.1	C12—C11—H11B	108.7
C3—C4—H4	119.4	C11—C12—H12A	109.2
C3—C4—C5	121.19 (13)	C11—C12—H12B	109.2
C5—C4—H4	119.4	C11—C12—C13	112.22 (12)
C2—C7—C8	106.87 (10)	H12A—C12—H12B	107.9
C6—C7—C2	118.39 (11)	C13—C12—H12A	109.2
C6—C7—C8	134.69 (12)	C13—C12—H12B	109.2
C4—C5—H5	119.4	C12—C13—H13A	109.5
C6—C5—C4	121.27 (13)	C12—C13—H13B	109.5
C6—C5—H5	119.4	C12—C13—H13C	109.5
C7—C6—H6	120.3	H13A—C13—H13B	109.5
C5—C6—C7	119.31 (12)	H13A—C13—H13C	109.5
C5—C6—H6	120.3	H13B—C13—H13C	109.5
C1—C8—C7	105.96 (10)	N2—C14—H14A	109.5
C1—C8—C9	127.19 (12)	N2—C14—H14B	109.5
C7—C8—C9	126.70 (11)	N2—C14—H14C	109.5
C8—C9—H9A	108.9	H14A—C14—H14B	109.5
C8—C9—H9B	108.9	H14A—C14—H14C	109.5
C8—C9—C10	113.30 (10)	H14B—C14—H14C	109.5

N1—C1—C8—C7	−0.41 (14)	C3—C2—C7—C6	−0.82 (18)
N1—C1—C8—C9	−176.10 (11)	C3—C2—C7—C8	−178.57 (11)
N1—C2—C3—C4	−177.51 (13)	C3—C4—C5—C6	−0.5 (2)
N1—C2—C7—C6	177.50 (11)	C4—C5—C6—C7	0.1 (2)
N1—C2—C7—C8	−0.25 (13)	C7—C2—C3—C4	0.40 (19)
N2—C11—C12—C13	−173.49 (12)	C7—C8—C9—C10	62.03 (17)
C1—N1—C2—C3	178.13 (13)	C6—C7—C8—C1	−176.81 (13)
C1—N1—C2—C7	0.00 (14)	C6—C7—C8—C9	−1.1 (2)
C1—C8—C9—C10	−123.14 (14)	C8—C7—C6—C5	177.52 (13)
C2—N1—C1—C8	0.27 (14)	C8—C9—C10—N2	−162.95 (10)
C2—C3—C4—C5	0.3 (2)	C10—N2—C11—C12	177.40 (11)
C2—C7—C6—C5	0.56 (18)	C11—N2—C10—C9	−74.78 (13)
C2—C7—C8—C1	0.40 (13)	C14—N2—C10—C9	161.94 (11)
C2—C7—C8—C9	176.12 (11)	C14—N2—C11—C12	−60.47 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.920 (17)	1.990 (17)	2.9097 (15)	179.8 (16)

Symmetry code: (i) −x+1/2, y+1/2, z.

Acknowledgements

Financial statements and conflict of interest: This study was funded by CaaMTech, LLC. ARC reports an ownership interest in CaaMTech, LLC, which has filed patent applications covering compositions of psilocybin derivatives.

Funding information

Funding for this research was provided by: National Science Foundation (grant No. CHE-1429086).

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