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

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ISSN: 2414-3146

N-Methyl-N-propyl­tryptamine (MPT)

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.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

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[Fontanilla, D., Johannessen, M., Hajipour, A. R., Cozzi, N. V., Jackson, M. B. & Ruoho, A. E. (2009). Science, 323, 934-937.]). 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[Aixalà, M., Dos Santos, R. G., Hallak, J. E. C. & Bouso, J. C. (2018). ACS Chem. Neurosci. 9, 2304-2306.]; Cameron et al., 2019[Cameron, L. P., Benson, C. J., DeFelice, B. C., Fiehn, O. & Olson, D. E. (2019). ACS Chem. Neurosci. In the press. http://doi.org/10.1021/acschemneuro.8b00692.]).

Psilocybin, isolated from the so-called `magic' mushrooms, is perhaps the best known prodrug of the serotonin 2a agonist psilocin (Nichols, 2016[Nichols, D. E. (2016). Pharmacol. Rev. 68, 264-355.]). 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[Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, V. H. & Nutt, D. J. (2016). Lancet Psychiatr. 3, 619-627.]; Johnson & Griffiths, 2017[Johnson, M. W. & Griffiths, R. R. (2017). Neurotherapeutics, 14, 734-740.]). 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[Passie, T., Seifert, J., Schneider, U. & Emrich, H. M. (2002). Addict. Biol. 7, 357-364.]). 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[Manske, R. H. F. (1931). Can. J. Res. 5, 592-600.]), the first literature report of MPT appeared in 2005 (Brandt et al., 2005[Brandt, S. D., Freeman, S., Fleet, I. A., McGagh, P. & Alder, J. F. (2005). Analyst, 130, 330-344.]) 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[link]). The metrical parameters are consistent with the previously reported structure of DMT (Falkenberg, 1972[Falkenberg, G. (1972). Acta Cryst. B28, 3075-3083.]) and other di­alkyl­tryptamines (Chadeayne et al., 2019a[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019a). Acta Cryst. E75, 900-902.],b[Chadeayne, A. R., Golen, J. A. & Manke, D. R. (2019b). Psychedel. Sci. Rev. https://psychedelicreview.com/the-crystal-structure-of-4-aco-dmt-fumarate/.]; Petcher & Weber, 1974[Petcher, T. J. & Weber, H. P. (1974). J. Chem. Soc. Perkin Trans. II, pp. 946-948.]; Weber & Petcher, 1974[Weber, H. P. & Petcher, T. J. (1974). J. Chem. Soc. Perkin Trans. II, pp. 942-946.]). 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[link], Fig. 2[link]). 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 ππ inter­actions observed in the structure.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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]
Figure 1
The mol­ecular structure of the title compound, showing the atomic labelling. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2]
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[link].

Table 2
Experimental details

Crystal data
Chemical formula C14H20N2
Mr 216.32
Crystal system, space group Orthorhombic, Pbca
Temperature (K) 200
a, b, c (Å) 13.5715 (11), 12.4352 (10), 15.1627 (12)
V3) 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[Bruker (2016). APEX3, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.713, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections 47431, 2350, 1942
Rint 0.048
(sin θ/λ)max−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
Δρmax, Δρmin (e Å−3) 0.17, −0.16
Computer programs: APEX3 and SAINT (Bruker, 2016[Bruker (2016). APEX3, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2014 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]) and 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.]).

Structural data


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
C14H20N2Dx = 1.123 Mg m3
Mr = 216.32Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PbcaCell parameters from 9106 reflections
a = 13.5715 (11) Åθ = 3.0–25.3°
b = 12.4352 (10) ŵ = 0.07 mm1
c = 15.1627 (12) ÅT = 200 K
V = 2558.9 (4) Å3Block, colourless
Z = 80.28 × 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 scansRint = 0.048
Absorption correction: multi-scan
(SADABS; Bruker, 2016)
θmax = 25.4°, θmin = 3.0°
Tmin = 0.713, Tmax = 0.745h = 1616
47431 measured reflectionsk = 1415
2350 independent reflectionsl = 1818
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.036 w = 1/[σ2(Fo2) + (0.040P)2 + 0.843P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.095(Δ/σ)max < 0.001
S = 1.05Δρmax = 0.17 e Å3
2350 reflectionsΔρmin = 0.16 e Å3
152 parametersExtinction correction: SHELXL2014 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction 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
xyzUiso*/Ueq
N10.15123 (8)0.54678 (9)0.71757 (7)0.0342 (3)
N20.47825 (7)0.22356 (7)0.76631 (7)0.0281 (3)
C10.20625 (9)0.48945 (10)0.77718 (8)0.0329 (3)
H1A0.20860.50400.83870.040*
C20.16536 (9)0.50319 (10)0.63560 (8)0.0299 (3)
C30.12410 (10)0.53092 (11)0.55460 (9)0.0380 (3)
H30.08020.59010.54940.046*
C40.14904 (10)0.46983 (12)0.48231 (9)0.0438 (4)
H40.12210.48730.42630.053*
C70.23153 (8)0.41566 (9)0.64465 (8)0.0291 (3)
C50.21333 (10)0.38242 (12)0.48980 (9)0.0427 (4)
H50.22880.34130.43890.051*
C60.25456 (10)0.35491 (11)0.56941 (9)0.0368 (3)
H60.29820.29540.57350.044*
C80.25697 (9)0.40901 (9)0.73654 (8)0.0299 (3)
C90.32024 (9)0.32514 (10)0.77938 (9)0.0347 (3)
H9A0.29020.25360.76960.042*
H9B0.32170.33820.84380.042*
C100.42572 (9)0.32375 (10)0.74460 (9)0.0334 (3)
H10A0.42450.33280.67970.040*
H10B0.46220.38540.76990.040*
C110.50645 (10)0.22182 (10)0.85999 (8)0.0341 (3)
H11A0.44650.23230.89620.041*
H11B0.55110.28320.87160.041*
C120.55691 (12)0.11938 (12)0.88919 (10)0.0473 (4)
H12A0.62110.11300.85850.057*
H12B0.51590.05700.87190.057*
C130.57384 (14)0.11646 (13)0.98776 (10)0.0574 (4)
H13A0.60890.05031.00340.086*
H13B0.51030.11841.01830.086*
H13C0.61330.17891.00540.086*
C140.56449 (10)0.21237 (11)0.70873 (9)0.0402 (3)
H14A0.54320.21250.64700.060*
H14B0.59820.14460.72190.060*
H14C0.60970.27260.71890.060*
H10.1103 (12)0.6027 (13)0.7328 (10)0.055 (5)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0332 (6)0.0297 (6)0.0396 (6)0.0077 (5)0.0033 (5)0.0054 (5)
N20.0232 (5)0.0262 (5)0.0350 (6)0.0004 (4)0.0003 (4)0.0002 (4)
C10.0321 (6)0.0317 (7)0.0350 (7)0.0017 (5)0.0026 (5)0.0024 (5)
C20.0248 (6)0.0282 (6)0.0365 (7)0.0018 (5)0.0000 (5)0.0019 (5)
C30.0322 (7)0.0386 (7)0.0434 (8)0.0002 (6)0.0045 (6)0.0023 (6)
C40.0412 (8)0.0546 (9)0.0356 (8)0.0068 (7)0.0034 (6)0.0001 (6)
C70.0231 (6)0.0255 (6)0.0386 (7)0.0031 (5)0.0019 (5)0.0019 (5)
C50.0422 (8)0.0479 (8)0.0380 (8)0.0059 (6)0.0052 (6)0.0103 (6)
C60.0320 (7)0.0335 (7)0.0448 (8)0.0010 (5)0.0055 (6)0.0074 (6)
C80.0252 (6)0.0263 (6)0.0383 (7)0.0011 (5)0.0005 (5)0.0000 (5)
C90.0298 (7)0.0302 (7)0.0442 (8)0.0033 (5)0.0023 (6)0.0047 (5)
C100.0273 (6)0.0286 (6)0.0441 (7)0.0015 (5)0.0006 (5)0.0065 (5)
C110.0339 (7)0.0307 (7)0.0377 (7)0.0007 (5)0.0048 (5)0.0025 (5)
C120.0545 (9)0.0413 (8)0.0462 (8)0.0095 (7)0.0089 (7)0.0019 (6)
C130.0701 (11)0.0508 (9)0.0514 (9)0.0043 (8)0.0200 (8)0.0090 (7)
C140.0288 (7)0.0439 (8)0.0478 (8)0.0014 (6)0.0060 (6)0.0007 (6)
Geometric parameters (Å, º) top
N1—C11.3722 (16)C8—C91.4991 (17)
N1—C21.3695 (16)C9—H9A0.9900
N1—H10.920 (17)C9—H9B0.9900
N2—C101.4727 (15)C9—C101.5257 (17)
N2—C111.4712 (15)C10—H10A0.9900
N2—C141.4668 (16)C10—H10B0.9900
C1—H1A0.9500C11—H11A0.9900
C1—C81.3618 (17)C11—H11B0.9900
C2—C31.3932 (18)C11—C121.5126 (18)
C2—C71.4177 (17)C12—H12A0.9900
C3—H30.9500C12—H12B0.9900
C3—C41.3759 (19)C12—C131.513 (2)
C4—H40.9500C13—H13A0.9800
C4—C51.398 (2)C13—H13B0.9800
C7—C61.4035 (17)C13—H13C0.9800
C7—C81.4377 (18)C14—H14A0.9800
C5—H50.9500C14—H14B0.9800
C5—C61.374 (2)C14—H14C0.9800
C6—H60.9500
C1—N1—H1123.8 (10)H9A—C9—H9B107.7
C2—N1—C1108.42 (10)C10—C9—H9A108.9
C2—N1—H1127.7 (10)C10—C9—H9B108.9
C11—N2—C10110.74 (10)N2—C10—C9112.74 (10)
C14—N2—C10109.48 (10)N2—C10—H10A109.0
C14—N2—C11111.45 (10)N2—C10—H10B109.0
N1—C1—H1A124.5C9—C10—H10A109.0
C8—C1—N1111.01 (11)C9—C10—H10B109.0
C8—C1—H1A124.5H10A—C10—H10B107.8
N1—C2—C3130.23 (12)N2—C11—H11A108.7
N1—C2—C7107.74 (11)N2—C11—H11B108.7
C3—C2—C7122.01 (12)N2—C11—C12114.38 (10)
C2—C3—H3121.1H11A—C11—H11B107.6
C4—C3—C2117.83 (13)C12—C11—H11A108.7
C4—C3—H3121.1C12—C11—H11B108.7
C3—C4—H4119.4C11—C12—H12A109.2
C3—C4—C5121.19 (13)C11—C12—H12B109.2
C5—C4—H4119.4C11—C12—C13112.22 (12)
C2—C7—C8106.87 (10)H12A—C12—H12B107.9
C6—C7—C2118.39 (11)C13—C12—H12A109.2
C6—C7—C8134.69 (12)C13—C12—H12B109.2
C4—C5—H5119.4C12—C13—H13A109.5
C6—C5—C4121.27 (13)C12—C13—H13B109.5
C6—C5—H5119.4C12—C13—H13C109.5
C7—C6—H6120.3H13A—C13—H13B109.5
C5—C6—C7119.31 (12)H13A—C13—H13C109.5
C5—C6—H6120.3H13B—C13—H13C109.5
C1—C8—C7105.96 (10)N2—C14—H14A109.5
C1—C8—C9127.19 (12)N2—C14—H14B109.5
C7—C8—C9126.70 (11)N2—C14—H14C109.5
C8—C9—H9A108.9H14A—C14—H14B109.5
C8—C9—H9B108.9H14A—C14—H14C109.5
C8—C9—C10113.30 (10)H14B—C14—H14C109.5
N1—C1—C8—C70.41 (14)C3—C2—C7—C60.82 (18)
N1—C1—C8—C9176.10 (11)C3—C2—C7—C8178.57 (11)
N1—C2—C3—C4177.51 (13)C3—C4—C5—C60.5 (2)
N1—C2—C7—C6177.50 (11)C4—C5—C6—C70.1 (2)
N1—C2—C7—C80.25 (13)C7—C2—C3—C40.40 (19)
N2—C11—C12—C13173.49 (12)C7—C8—C9—C1062.03 (17)
C1—N1—C2—C3178.13 (13)C6—C7—C8—C1176.81 (13)
C1—N1—C2—C70.00 (14)C6—C7—C8—C91.1 (2)
C1—C8—C9—C10123.14 (14)C8—C7—C6—C5177.52 (13)
C2—N1—C1—C80.27 (14)C8—C9—C10—N2162.95 (10)
C2—C3—C4—C50.3 (2)C10—N2—C11—C12177.40 (11)
C2—C7—C6—C50.56 (18)C11—N2—C10—C974.78 (13)
C2—C7—C8—C10.40 (13)C14—N2—C10—C9161.94 (11)
C2—C7—C8—C9176.12 (11)C14—N2—C11—C1260.47 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···N2i0.920 (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).

References

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