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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 82| Part 9| September 2026| Pages 1082-1086
https://doi.org/10.1107/S2056989026008571

Syntheses and structures of two norpsilocin derivatives: N-ethyl-4-hy­dr­oxy­tryptamine (4-HO-NET) and 4-hy­dr­oxy-N-propyl­tryptamine (4-HO-NPT)

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Marilyn Naeem,a Andrew R. Chadeayne,b James A. Golena and David R. Mankea*

aUniversity of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747, USA, and bCaaMTech, Inc., 58 Sunset Way, Suite 209, Issaquah, WA 98027, USA
*Correspondence e-mail: [email protected]

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 16 August 2026; accepted 18 August 2026; online 25 August 2026)

The solid-state structures of N-ethyl-4-hy­droxy­tryptamine (4-HO-NET) {systematic name: 3-[2-(ethyl­amino)­eth­yl]-1H-indol-4-ol}, C12H16N2O, and 4-hy­droxy-N-propyl­tryptamine (4-HO-NPT) {systematic name: 3-[2-(propyl­amino)­eth­yl]-1H-indol-4-ol}, C13H18N2O, are reported. Both compounds possess a single tryptamine mol­ecule in the asymmetric unit that exhibits an inter­nal O—H⋯N hydrogen bond. In the extended structures, the mol­ecules are linked by N—H⋯O hydrogen bonds to form infinite chains along [001] for 4-HO-NET and along [101] for 4-HO-NPT.

CCDC references: 2581888; 2581887

Similar articles

1. Chemical context

Traditional psychoactive compounds including psilocybin (4-phosphor­yloxy-N,N-di­methyl­tryptamine; C12H17N2O4P), psilocin (4-hy­droxy-N,N-di­methyl­tryptamine; C12H16N2O), DMT (N,N-di­methyl­tryptamine; C12H16N2), and 5-MeO-DMT (5-meth­oxy-N,N-di­methyl­tryptamine; C13H18N2O) are all based upon an N,N-di­alkyl­tryptamine backbone. Lesser known naturally occurring compounds such as baeocystin (4-phosphor­yloxy-N-methyl­tryptamine; C11H15N2O4P) and norpsilocin (4-hy­droxy-N-methyl­tryptamine; C11H14N2O) have a suggested biological relevance but an underdeveloped chemistry. We have previously reported the crystal structures of both of these N-mono­alkyl­tryptamine compounds (Naeem et al., 2022View full citation; Chadeayne et al., 2020bView full citation), as well as explored their pharmacological properties (Glatfelter, Pottie et al., 2022View full citation). The removal of a single methyl group from the traditional N,N-di­methyl­tryptamines can significantly alter lipophilicity, central nervous system exposure, metabolism, receptor activity and transporter pharmacology. The N-mono­alkyl­tryptamines are a group of serotonergic chemicals that could present pharmacology not accessible through the class of N,N-di­alkyl­tryptamines. In early 2023, we reported the synthesis and structure of 4-hy­droxy-N-iso­propyl­tryptamine (4-HO-NiPT) as the first direct N-alkyl analogue of norpsilocin (Laban et al., 2023View full citation). Sherwood and co-workers later reported a number of other N-alkyl analogues, exploring their pharmacology. Of note, derivatives of norpsilocin where the steric bulk of the alkyl group was increased (i.e. 4-HO-NiPT) showed psychoactive effects in animal models (Sherwood et al., 2024View full citation). We recently reported the 4-meth­oxy variant of norpsilocin, as well as other 4-meth­oxy mono-N-alkyl derivatives, which were shown to be potent 5-HT2A agonists with reduced psychedelic-like effects in animal models (Glatfelter, Schalk et al., 2026View full citation). Herein, we report the syntheses and structures of two norpsilocin analogues, N-ethyl-4-hy­droxy­tryptamine (4-HO-NET; C12H16N2O) and 4-hy­droxy-N-prop­yl­tryptamine (4-HO-NPT; C13H18N2O).

[Scheme 1]

2. Structural commentary

The mol­ecular structures of 4-HO-NET and 4-HO-NPT are shown in Fig. 1[link]. The asymmetric unit of each structure contains a single tryptamine mol­ecule. The side chain in 4-HO-NET displays an extended conformation, as shown by the C9—C10—N2—C11 and C10—N2—C11—C12 torsion angles of −174.88 (12) and −174.34 (14)°, respectively. The longer side chain in 4-HO-NPT shows a more twisted conformation with C9—C10—N2—C11 = −101.41 (15), C10—N1—C11—C12 = 174.61 (13) and N2—C11—C12—C13 = 169.17 (13)°.

[Figure 1]
Figure 1
The mol­ecular structures of 4-HO-NET (left) and 4-HO-NPT (right) with displacement ellipsoids drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines.

Both mol­ecules possess an inter­nal O—H⋯N hydrogen bond between the phenol oxygen atom (O1) and the acyclic amine nitro­gen atom (N2), which generates an S(8) ring in each case. As expected, both C1–C8/N1 indole ring systems are near planar, showing a r.m.s. deviation of 0.009Å for 4-HO-NET and 0.011Å for 4-HO-NPT.

3. Supra­molecular features

In the solid-state structure of 4-HO-NET, the mol­ecules are linked by N1—H1A⋯O1 hydrogen bonds between the indole N—H grouping and the hydroxide group. These hydrogen bonds link the mol­ecules into infinite chains propagating along the [001] direction (Table 1[link]). The crystal packing of 4-HO-NET is shown on the left in Fig. 2[link].

Table 1
Hydrogen-bond geometry (Å, °) for 4-HO-NET[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1A⋯O1i 0.87 (1) 2.06 (1) 2.8789 (15) 158 (2)
O1—H1⋯N2 1.00 (1) 1.58 (1) 2.5764 (16) 173 (2)
Symmetry code: (i) Mathematical equation.
[Figure 2]
Figure 2
The crystal packing of 4-HO-NET (left) and 4-HO-NPT (right), both shown along the a-axis direction. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bonding are omitted for clarity.

In the extended structure of 4-HO-NPT, two mol­ecules are connected through N2—H2⋯O1 hydrogen bonds. These inter­molecular hydrogen bonds combine with the O1—H1⋯N2 intra­molecular hydrogen bonds to form rings demonstrating a graph set notation of R22(16) (Etter et al., 1990View full citation). These dimers are then joined together through the indole N1—H1A⋯O1 hydrogen bond to the next dimer, forming infinite chains propagating along the [101] direction (Table 2[link]). The crystal packing of 4-HO-NPT is shown on the right in Fig. 2[link].

Table 2
Hydrogen-bond geometry (Å, °) for 4-HO-NPT[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O1—H1⋯N2 1.01 (1) 1.59 (1) 2.5905 (15) 175 (2)
N1—H1A⋯O1i 0.87 (1) 2.06 (1) 2.9347 (16) 177 (2)
N2—H2⋯O1ii 0.90 (1) 2.62 (1) 3.4957 (17) 166 (2)
Symmetry codes: (i) Mathematical equation; (ii) Mathematical equation.

4. Database survey

The structures of mono­alkyl­tryptamines are not common in the Cambridge Structural Database, with only ten crystal structures previously reported, all in the past few years. These include the natural product baeocystin (Naeem et al., 2022View full citation; FETBAB), its hydrolysis product norpsilocin as its freebase and fumarate salt (Chadeayne et al., 2020bView full citation; MULXAV, MULXEZ) and the synthetic prodrug of norpsilocin, 4-acet­oxy-N-methyl­tryptamine (Glatfelter, Pottie et al., 2022View full citation). The others are N-methyl­serotonin as its hydrogen oxalate salt (Naeem, Anas et al., 2023View full citation), 4-benzyl-N-iso­propyl­tryptamine, 4-hy­droxy-N-iso­propyl­tryptamine (Laban et al., 2023View full citation3; YEYZIP, YEYZOV), and the freebase, bromide and fumarate salts of N-cyclo­hexyl­tryptamine (Naeem, Le et al., 2023View full citation; YITWAD, YITWEH, YITWIL).

There are eight 4-hy­droxy-N,N-di­alkyl­tryptamine crystal structures reported in the literature, which are 4-hy­droxy-N-methyl-N-iso­propyl­tryptamine as its fumarate (Chadeayne et al., 2020aView full citation; TUFQAP) and hydro­fumarate (Chadeayne et al., 2019aView full citation; RONSUL), 4-hy­droxy-N,N-di­propyl­tryptamine as its fumarate (Chadeayne et al., 2019bView full citation; WUCGAF) and chloride (Sammeta et al., 2020View full citation; WAMGEA) salts, 4-hy­droxy-N,N-diiso­propyl­tryptamine as its hydro­fumarate salt (Naeem et al., 2025View full citation; BOWSOF), and the natural product psilocin as its freebase (Petcher & Weber, 1974View full citation; PSILIN; Zeller et al., 2024View full citation; PSILIN03), its tatrate salt (Barrow et al., 2025View full citation; XOWXIU), and as a co-crystal with the natural product psilocybin (Silverstone, 2024View full citation; MIMKOM). There are also four 4-hy­droxy-N,N,N-tri­alkyl­tryptamine crystal structures reported including 4-hy­droxy-N,N,N-tri­methyl­tryptamine (Chadeayne et al., 2020cView full citation; XUXFAA), 4-hy­droxy-N,N-dimethyl-N-ethyl­tryptamine, 4-hy­droxy-N,N-dimethyl-N-propyl­tryptamine, and 4-hy­droxy-N,N-dimethyl-N-iso­propyl­tryptamine (Glatfelter, Pham et al., 2022View full citation; EDOYIJ, EDOYUV, EDOZEG).

5. Synthesis and crystallization

4-HO-NET: To an ice-bath-cooled diethyl ether (60 ml) solution of 4-benz­yloxy-1H-indole (3.0 g) was added oxalylchloride (3.4 g) dropwise. The mixture was stirred in the ice bath for 6 h and then added dropwise to an ice-bath-cooled solution of 70% aqueous ethyl­amine (5.8 g). The mixture was warmed to room temperature and stirred overnight. The resulting suspension was concentrated under reduced pressure and the residue was purified by silica gel chromatography (methyl­ene chloride/methanol) to afford 2-(4-benz­yloxy)-1H-indol-3-yl)-N-ethyl-2-oxoacetamide as a yellow oil (3.2 g). The yellow oil was dissolved in tetra­hydro­furan (50 ml), cooled in an ice bath, and 30 ml of 1 M borane-tetra­hydro­furan was added dropwise. The mixture was heated at reflux overnight. The resulting yellow solution was quenched with 2 M hydro­chloric acid and heated at reflux for 2 h. The mixture was cooled and ammonium hydroxide was added until the solution was basic. The resulting mixture was extracted with methyl­ene chloride; the organic layer was washed with water and brine, and then dried over sodium sulfate. Solvent was removed in vacuo and the resulting residue was purified by silica gel chromatography [methyl­ene chloride/methanol (3.5 M ammonia)] to afford 4-benz­yloxy-N-ethyl­tryptamine (4-BnO-NET) as a yellow solid (1.6 g, 54% yield). To a solution of 4-BnO-NET (600 mg) in methanol (12 ml) was added Pd/C (120 mg) and Pd(OH)2/C (120 mg). The mixture was stirred for 3 h under a hydrogen atmosphere. The resulting black suspension was filtered, the solid was washed with methanol, and the combined filtrates were concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography [methyl­ene chloride/methanol (3.5 M ammonia)] to afford 4-hy­droxy-N-ethyl­tryptamine (4-HO-NET) as a white solid (162 mg, 39% yield). Single crystals suitable for X-ray diffraction were grown from the slow evaporation of an acetone solution.

4-HO-NPT: To an ice bath-cooled diethyl ether (40 ml) solution of 4-benz­yloxy-1H-indole (2.0 g) was added oxalylchloride (2.3 g) dropwise. The mixture was stirred for 6 h under cooling, and then added dropwise into an ice-bath cooled vessel containing propan-1-amine (5.3 g). The mixture was warmed to room temperature and stirred overnight. The solvent was removed in vacuo and the resulting residue was purified by silica gel chromatography (methyl­ene chloride/methanol) to afford 2-(4-benz­yloxy-1H-indol-3-yl)-2-oxo-N-propyl­acetamide as a yellow oil (1 g, 33% yield). This yellow oil was dissolved in tetra­hydro­furan (15 ml) and cooled in an ice bath, then 9 ml of 1.0 M borane-tetra­hydro­furan in tetra­hydro­furan was added dropwise. The mixture was heated at reflux for 2 h, cooled to room temperature, and then ammonium hydroxide was added until it was basic. The mixture was extracted with methyl­ene chloride and the organic phase was washed with water and brine. It was dried over sodium sulfate, then solvent was removed in vacuo, and purified by silica gel chromatography to yield 4-benz­yloxy-N-propyl­tryptamine (4-BnO-NPT) as a yellow solid (192 mg, 21% yield). To a solution of 4-BnO-NPT (190 mg) in methanol (4 ml) was added Pd/C (40 mg) and Pd(OH)2/C (40 mg). The mixture was stirred for 3 h under a hydrogen atmosphere. The resulting black suspension was filtered, the solid was washed with methanol, and the combined filtrates were concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography [methyl­ene chloride/methanol (3.5 M ammonia)] to afford 4-hy­droxy-N-propyl­tryptamine (4-HO-NPT) as a white solid (75 mg, 55% yield). Single crystals suitable for X-ray diffraction studies were grown from the slow evaporation of an acetone solution.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. N- and O-bound H atoms were refined with restrained distances. C-bound H atoms were positioned geometrically (0.93–0.97 Å) and refined as riding with Uiso(H) = 1.2–1.5Ueq(C).

Table 3
Experimental details

  4-HO-NET 4-HO-NPT
Crystal data
Chemical formula C12H16N2O C13H18N2O
Mr 204.27 218.29
Crystal system, space group Monoclinic, P21/c Monoclinic, P21/n
Temperature (K) 300 300
a, b, c (Å) 8.3887 (5), 9.0776 (5), 14.5657 (9) 9.0478 (6), 11.6680 (8), 11.3885 (7)
β (°) 100.132 (2) 91.523 (2)
V (Å3) 1091.87 (11) 1201.86 (14)
Z 4 4
F(000) 440 472
Dx (Mg m−3) 1.243 1.206
Radiation type Mo Kα Mo Kα
No. of reflections for cell measurement 9957 8762
θ range (°) for cell measurement 2.7–26.3 2.8–26.4
μ (mm−1) 0.08 0.08
Crystal shape Block Block
Colour Yellow Colourless
Crystal size (mm) 0.27 × 0.21 × 0.20 0.24 × 0.22 × 0.21
 
Data collection
Diffractometer Bruker D8 Venture CMOS Bruker D8 Venture CMOS
Scan method φ and ω scans φ and ω scans
Absorption correction Multi-scan (SADABS; Krause et al., 2015View full citation) Multi-scan (SADABS; Krause et al., 2015View full citation)
Tmin, Tmax 0.704, 0.745 0.705, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections 23801, 2243, 1953 34791, 2472, 1941
Rint 0.028 0.040
(sin θ/λ)max (Å−1) 0.625 0.626
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.112, 1.05 0.038, 0.107, 1.01
No. of reflections 2243 2472
No. of parameters 150 159
No. of restraints 3 3
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.25, −0.13 0.14, −0.11
Computer programs: APEX3 and SAINT (Bruker, 2021View full citation), SHELXT2014 (Sheldrick, 2015aView full citation), SHELXL2018 (Sheldrick, 2015bView full citation), OLEX2 (Dolomanov et al., 2009View full citation) and publCIF (Westrip, 2010View full citation).

Supporting information

CCDC references: 2581888; 2581887

Crystal structure: contains datablocks global, 4-HO-NPT, 4-HO-NET. DOI: https://doi.org/10.1107/S2056989026008571/hb8250sup1.cif

Structure factors: contains datablock 4-HO-NET. DOI: https://doi.org/10.1107/S2056989026008571/hb82504-HO-NETsup4.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989026008571/hb82504-HO-NETsup4.cml

Structure factors: contains datablock 4-HO-NPT. DOI: https://doi.org/10.1107/S2056989026008571/hb82504-HO-NPTsup5.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989026008571/hb82504-HO-NPTsup5.cml

checkCIF report


Computing details top

3-[2-(Ethylamino)ethyl]-1H-indol-4-ol (4-HO-NET) top
Crystal data top
C12H16N2OF(000) = 440
Mr = 204.27Dx = 1.243 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 8.3887 (5) ÅCell parameters from 9957 reflections
b = 9.0776 (5) Åθ = 2.7–26.3°
c = 14.5657 (9) ŵ = 0.08 mm−1
β = 100.132 (2)°T = 300 K
V = 1091.87 (11) Å3Block, yellow
Z = 40.27 × 0.21 × 0.20 mm
Data collection top
Bruker D8 Venture CMOS
diffractometer		1953 reflections with I > 2σ(I)
φ and ω scansRint = 0.028
Absorption correction: multi-scan
(SADABS; Krause et al., 2015)		θmax = 26.4°, θmin = 2.7°
Tmin = 0.704, Tmax = 0.745h = −10→10
23801 measured reflectionsk = −11→11
2243 independent reflectionsl = −18→18
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)] = 0.040 w = 1/[σ2(Fo2) + (0.0518P)2 + 0.3161P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.112(Δ/σ)max < 0.001
S = 1.05Δρmax = 0.25 e Å−3
2243 reflectionsΔρmin = −0.13 e Å−3
150 parametersExtinction correction: SHELXL2018 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
3 restraintsExtinction coefficient: 0.007 (2)
Primary atom site location: dual
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
O10.26670 (16)0.64120 (12)0.59539 (6)0.0558 (3)
N10.24109 (16)0.75788 (14)0.90599 (8)0.0457 (3)
N20.35265 (16)0.37322 (13)0.63603 (9)0.0457 (3)
C10.32861 (17)0.63081 (16)0.90504 (9)0.0425 (3)
H1B0.3736000.5782300.9580990.051*
C20.19401 (15)0.80509 (14)0.81596 (9)0.0365 (3)
C30.10539 (17)0.93092 (16)0.78357 (10)0.0444 (3)
H30.0686800.9963950.8243330.053*
C40.07518 (17)0.95333 (16)0.68926 (11)0.0462 (4)
H40.0173171.0362820.6653000.055*
C50.12934 (17)0.85438 (15)0.62827 (10)0.0439 (3)
H50.1057850.8727980.5645160.053*
C60.21698 (16)0.72971 (14)0.65966 (9)0.0362 (3)
C70.25324 (14)0.70272 (13)0.75676 (8)0.0313 (3)
C80.34133 (15)0.59139 (14)0.81676 (9)0.0354 (3)
C90.43485 (16)0.45785 (15)0.79633 (10)0.0422 (3)
H9A0.4801050.4115680.8551780.051*
H9B0.5248600.4904990.7678070.051*
C100.34164 (18)0.34175 (15)0.73357 (10)0.0451 (3)
H10A0.3863530.2450390.7507290.054*
H10B0.2290640.3420040.7411660.054*
C110.2549 (2)0.2752 (2)0.56823 (13)0.0634 (5)
H11A0.1409250.2901580.5699640.076*
H11B0.2813280.1734800.5846680.076*
C120.2861 (3)0.3053 (2)0.47154 (13)0.0805 (6)
H12A0.2196420.2417690.4279830.121*
H12B0.3981390.2871780.4693470.121*
H12C0.2605720.4061870.4554880.121*
H1A0.229 (2)0.8046 (19)0.9562 (9)0.067 (5)*
H10.301 (2)0.5388 (13)0.6159 (14)0.086 (6)*
H20.4583 (12)0.3621 (19)0.6293 (12)0.062 (5)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0953 (9)0.0449 (6)0.0303 (5)0.0192 (6)0.0194 (5)0.0045 (4)
N10.0593 (7)0.0476 (7)0.0307 (6)0.0011 (6)0.0096 (5)−0.0077 (5)
N20.0504 (7)0.0407 (6)0.0468 (7)0.0037 (5)0.0102 (5)−0.0051 (5)
C10.0493 (8)0.0449 (7)0.0316 (6)−0.0017 (6)0.0026 (5)0.0025 (5)
C20.0374 (6)0.0373 (7)0.0355 (6)−0.0048 (5)0.0084 (5)−0.0039 (5)
C30.0433 (7)0.0399 (7)0.0518 (8)0.0043 (6)0.0126 (6)−0.0084 (6)
C40.0419 (7)0.0383 (7)0.0576 (9)0.0073 (6)0.0067 (6)0.0052 (6)
C50.0491 (8)0.0437 (7)0.0377 (7)0.0039 (6)0.0046 (6)0.0064 (6)
C60.0426 (7)0.0344 (6)0.0324 (6)−0.0008 (5)0.0088 (5)0.0010 (5)
C70.0319 (6)0.0308 (6)0.0320 (6)−0.0038 (5)0.0074 (5)0.0000 (5)
C80.0374 (6)0.0358 (6)0.0331 (6)−0.0028 (5)0.0063 (5)0.0021 (5)
C90.0438 (7)0.0401 (7)0.0424 (7)0.0062 (6)0.0065 (6)0.0060 (6)
C100.0524 (8)0.0341 (7)0.0512 (8)0.0051 (6)0.0159 (6)0.0025 (6)
C110.0675 (11)0.0538 (9)0.0665 (11)0.0006 (8)0.0049 (8)−0.0181 (8)
C120.1077 (17)0.0721 (13)0.0539 (10)0.0148 (12)−0.0069 (10)−0.0130 (9)
Geometric parameters (Å, º) top
O1—C61.3539 (16)C5—H50.9300
O1—H11.003 (9)C5—C61.3827 (19)
N1—C11.3687 (19)C6—C71.4147 (17)
N1—C21.3700 (17)C7—C81.4506 (17)
N1—H1A0.867 (9)C8—C91.5018 (18)
N2—C101.4679 (19)C9—H9A0.9700
N2—C111.468 (2)C9—H9B0.9700
N2—H20.914 (9)C9—C101.519 (2)
C1—H1B0.9300C10—H10A0.9700
C1—C81.3569 (18)C10—H10B0.9700
C2—C31.3988 (19)C11—H11A0.9700
C2—C71.4159 (17)C11—H11B0.9700
C3—H30.9300C11—C121.502 (3)
C3—C41.368 (2)C12—H12A0.9600
C4—H40.9300C12—H12B0.9600
C4—C51.394 (2)C12—H12C0.9600
C6—O1—H1116.7 (12)C1—C8—C7105.70 (11)
C1—N1—C2108.59 (11)C1—C8—C9122.11 (12)
C1—N1—H1A124.3 (13)C7—C8—C9132.18 (11)
C2—N1—H1A126.7 (13)C8—C9—H9A108.1
C10—N2—H2108.0 (11)C8—C9—H9B108.1
C11—N2—C10114.23 (13)C8—C9—C10116.60 (11)
C11—N2—H2107.4 (11)H9A—C9—H9B107.3
N1—C1—H1B124.3C10—C9—H9A108.1
C8—C1—N1111.32 (12)C10—C9—H9B108.1
C8—C1—H1B124.3N2—C10—C9109.52 (11)
N1—C2—C3128.68 (12)N2—C10—H10A109.8
N1—C2—C7107.74 (11)N2—C10—H10B109.8
C3—C2—C7123.58 (12)C9—C10—H10A109.8
C2—C3—H3121.5C9—C10—H10B109.8
C4—C3—C2116.99 (12)H10A—C10—H10B108.2
C4—C3—H3121.5N2—C11—H11A109.5
C3—C4—H4119.3N2—C11—H11B109.5
C3—C4—C5121.37 (13)N2—C11—C12110.58 (16)
C5—C4—H4119.3H11A—C11—H11B108.1
C4—C5—H5119.0C12—C11—H11A109.5
C6—C5—C4122.04 (13)C12—C11—H11B109.5
C6—C5—H5119.0C11—C12—H12A109.5
O1—C6—C5117.88 (12)C11—C12—H12B109.5
O1—C6—C7123.38 (11)C11—C12—H12C109.5
C5—C6—C7118.72 (12)H12A—C12—H12B109.5
C2—C7—C8106.65 (11)H12A—C12—H12C109.5
C6—C7—C2117.29 (11)H12B—C12—H12C109.5
C6—C7—C8136.06 (11)
O1—C6—C7—C2179.68 (12)C3—C2—C7—C6−1.21 (19)
O1—C6—C7—C80.0 (2)C3—C2—C7—C8178.54 (12)
N1—C1—C8—C7−0.41 (15)C3—C4—C5—C6−0.5 (2)
N1—C1—C8—C9178.50 (12)C4—C5—C6—O1−178.97 (13)
N1—C2—C3—C4179.56 (14)C4—C5—C6—C7−0.4 (2)
N1—C2—C7—C6179.46 (11)C5—C6—C7—C21.16 (18)
N1—C2—C7—C8−0.79 (14)C5—C6—C7—C8−178.49 (13)
C1—N1—C2—C3−178.73 (14)C6—C7—C8—C1−179.60 (14)
C1—N1—C2—C70.55 (15)C6—C7—C8—C91.7 (2)
C1—C8—C9—C10121.65 (15)C7—C2—C3—C40.4 (2)
C2—N1—C1—C8−0.08 (16)C7—C8—C9—C10−59.77 (19)
C2—C3—C4—C50.5 (2)C8—C9—C10—N290.62 (14)
C2—C7—C8—C10.73 (14)C10—N2—C11—C12−174.34 (14)
C2—C7—C8—C9−178.02 (13)C11—N2—C10—C9−174.88 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.87 (1)2.06 (1)2.8789 (15)158 (2)
O1—H1···N21.00 (1)1.58 (1)2.5764 (16)173 (2)
Symmetry code: (i) x, −y+3/2, z+1/2.
3-[2-(Propylamino)ethyl]-1H-indol-4-ol (4-HO-NPT) top
Crystal data top
C13H18N2OF(000) = 472
Mr = 218.29Dx = 1.206 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 9.0478 (6) ÅCell parameters from 8762 reflections
b = 11.6680 (8) Åθ = 2.8–26.4°
c = 11.3885 (7) ŵ = 0.08 mm−1
β = 91.523 (2)°T = 300 K
V = 1201.86 (14) Å3Block, colourless
Z = 40.24 × 0.22 × 0.21 mm
Data collection top
Bruker D8 Venture CMOS
diffractometer		1941 reflections with I > 2σ(I)
φ and ω scansRint = 0.040
Absorption correction: multi-scan
(SADABS; Krause et al., 2015)		θmax = 26.4°, θmin = 2.8°
Tmin = 0.705, Tmax = 0.745h = −11→11
34791 measured reflectionsk = −14→14
2472 independent reflectionsl = −14→14
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)] = 0.038 w = 1/[σ2(Fo2) + (0.0476P)2 + 0.2229P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.107(Δ/σ)max < 0.001
S = 1.01Δρmax = 0.14 e Å−3
2472 reflectionsΔρmin = −0.11 e Å−3
159 parametersExtinction correction: SHELXL2018 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
3 restraintsExtinction coefficient: 0.010 (2)
Primary atom site location: dual
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
O10.67289 (11)0.65319 (8)0.46631 (9)0.0625 (3)
N10.37615 (16)0.73704 (13)0.13702 (12)0.0744 (4)
N20.65373 (13)0.43935 (10)0.40664 (11)0.0581 (3)
C10.4626 (2)0.64513 (15)0.11322 (13)0.0727 (5)
H1B0.4595620.6053650.0424280.087*
C20.41003 (15)0.77475 (12)0.24805 (12)0.0555 (4)
C30.35237 (17)0.86658 (14)0.30944 (15)0.0664 (4)
H30.2792870.9133940.2762890.080*
C40.40760 (18)0.88524 (13)0.42067 (15)0.0683 (4)
H40.3725850.9469060.4635570.082*
C50.51543 (17)0.81379 (12)0.47138 (13)0.0610 (4)
H50.5498390.8284810.5475720.073*
C60.57192 (14)0.72214 (11)0.41115 (11)0.0474 (3)
C70.52103 (13)0.70145 (11)0.29519 (11)0.0459 (3)
C80.55428 (15)0.61854 (12)0.20607 (11)0.0549 (3)
C90.66469 (18)0.52272 (14)0.20690 (13)0.0671 (4)
H9A0.7590080.5524620.2356460.081*
H9B0.6775180.4976380.1266090.081*
C100.62556 (19)0.41950 (13)0.28017 (15)0.0703 (4)
H10A0.5218830.4012140.2668630.084*
H10B0.6832370.3542070.2552790.084*
C110.79192 (15)0.38631 (13)0.45205 (14)0.0606 (4)
H11A0.8735370.4111090.4047060.073*
H11B0.7841250.3036400.4454300.073*
C120.82328 (17)0.41798 (14)0.57805 (14)0.0652 (4)
H12A0.7339160.4071450.6219280.078*
H12B0.8487460.4986690.5819580.078*
C130.9464 (2)0.34963 (17)0.63607 (16)0.0825 (5)
H13A0.9601980.3742690.7160390.124*
H13B1.0361300.3614000.5946050.124*
H13C0.9211940.2697110.6345080.124*
H10.664 (2)0.5715 (10)0.4388 (17)0.109 (7)*
H1A0.3140 (18)0.7706 (16)0.0882 (14)0.097 (6)*
H20.5807 (16)0.4070 (15)0.4476 (15)0.089 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0740 (6)0.0542 (6)0.0577 (6)0.0054 (5)−0.0287 (5)−0.0068 (4)
N10.0834 (9)0.0706 (9)0.0672 (8)−0.0035 (7)−0.0373 (7)0.0081 (7)
N20.0528 (7)0.0504 (7)0.0708 (8)0.0000 (5)−0.0054 (6)−0.0020 (6)
C10.0961 (12)0.0687 (10)0.0517 (8)−0.0093 (9)−0.0259 (8)−0.0037 (7)
C20.0519 (7)0.0557 (8)0.0581 (8)−0.0098 (6)−0.0138 (6)0.0105 (6)
C30.0568 (8)0.0571 (9)0.0849 (11)0.0028 (7)−0.0074 (7)0.0147 (8)
C40.0762 (10)0.0531 (8)0.0759 (10)0.0061 (7)0.0057 (8)−0.0005 (7)
C50.0782 (10)0.0525 (8)0.0519 (8)−0.0015 (7)−0.0044 (7)−0.0035 (6)
C60.0495 (7)0.0453 (7)0.0469 (7)−0.0073 (5)−0.0082 (5)0.0020 (5)
C70.0434 (6)0.0478 (7)0.0460 (7)−0.0104 (5)−0.0061 (5)0.0038 (5)
C80.0598 (8)0.0582 (8)0.0462 (7)−0.0103 (6)−0.0092 (6)−0.0018 (6)
C90.0679 (9)0.0782 (11)0.0548 (8)0.0017 (8)−0.0053 (7)−0.0182 (7)
C100.0737 (10)0.0549 (9)0.0810 (11)0.0047 (7)−0.0234 (8)−0.0175 (8)
C110.0556 (8)0.0516 (8)0.0741 (10)0.0037 (6)−0.0053 (7)0.0035 (7)
C120.0639 (9)0.0655 (9)0.0661 (9)−0.0032 (7)−0.0010 (7)0.0121 (7)
C130.0751 (11)0.0896 (13)0.0819 (11)−0.0025 (9)−0.0155 (9)0.0224 (10)
Geometric parameters (Å, º) top
O1—C61.3587 (15)C6—C71.4078 (16)
O1—H11.006 (9)C7—C81.4397 (19)
N1—C11.359 (2)C8—C91.499 (2)
N1—C21.3659 (19)C9—H9A0.9700
N1—H1A0.873 (9)C9—H9B0.9700
N2—C101.474 (2)C9—C101.513 (2)
N2—C111.4762 (18)C10—H10A0.9700
N2—H20.902 (9)C10—H10B0.9700
C1—H1B0.9300C11—H11A0.9700
C1—C81.3623 (19)C11—H11B0.9700
C2—C31.389 (2)C11—C121.501 (2)
C2—C71.4142 (18)C12—H12A0.9700
C3—H30.9300C12—H12B0.9700
C3—C41.367 (2)C12—C131.508 (2)
C4—H40.9300C13—H13A0.9600
C4—C51.397 (2)C13—H13B0.9600
C5—H50.9300C13—H13C0.9600
C5—C61.3763 (19)
C6—O1—H1111.6 (12)C8—C9—H9A108.4
C1—N1—C2108.83 (12)C8—C9—H9B108.4
C1—N1—H1A126.3 (13)C8—C9—C10115.57 (13)
C2—N1—H1A124.7 (13)H9A—C9—H9B107.4
C10—N2—C11113.53 (12)C10—C9—H9A108.4
C10—N2—H2109.3 (12)C10—C9—H9B108.4
C11—N2—H2105.6 (12)N2—C10—C9112.14 (12)
N1—C1—H1B124.2N2—C10—H10A109.2
N1—C1—C8111.52 (14)N2—C10—H10B109.2
C8—C1—H1B124.2C9—C10—H10A109.2
N1—C2—C3129.54 (13)C9—C10—H10B109.2
N1—C2—C7107.23 (13)H10A—C10—H10B107.9
C3—C2—C7123.23 (13)N2—C11—H11A109.3
C2—C3—H3121.4N2—C11—H11B109.3
C4—C3—C2117.17 (14)N2—C11—C12111.62 (13)
C4—C3—H3121.4H11A—C11—H11B108.0
C3—C4—H4119.3C12—C11—H11A109.3
C3—C4—C5121.49 (15)C12—C11—H11B109.3
C5—C4—H4119.3C11—C12—H12A108.7
C4—C5—H5119.3C11—C12—H12B108.7
C6—C5—C4121.49 (13)C11—C12—C13114.03 (14)
C6—C5—H5119.3H12A—C12—H12B107.6
O1—C6—C5118.93 (11)C13—C12—H12A108.7
O1—C6—C7122.09 (12)C13—C12—H12B108.7
C5—C6—C7118.96 (12)C12—C13—H13A109.5
C2—C7—C8107.36 (11)C12—C13—H13B109.5
C6—C7—C2117.62 (12)C12—C13—H13C109.5
C6—C7—C8135.02 (12)H13A—C13—H13B109.5
C1—C8—C7105.06 (13)H13A—C13—H13C109.5
C1—C8—C9124.52 (14)H13B—C13—H13C109.5
C7—C8—C9130.41 (12)
O1—C6—C7—C2176.68 (11)C3—C2—C7—C61.52 (19)
O1—C6—C7—C8−2.7 (2)C3—C2—C7—C8−178.94 (13)
N1—C1—C8—C70.13 (18)C3—C4—C5—C60.7 (2)
N1—C1—C8—C9−179.06 (14)C4—C5—C6—O1−177.74 (13)
N1—C2—C3—C4−179.79 (15)C4—C5—C6—C71.0 (2)
N1—C2—C7—C6−178.60 (12)C5—C6—C7—C2−2.00 (18)
N1—C2—C7—C80.94 (15)C5—C6—C7—C8178.62 (14)
N2—C11—C12—C13169.17 (13)C6—C7—C8—C1178.77 (15)
C1—N1—C2—C3179.00 (15)C6—C7—C8—C9−2.1 (3)
C1—N1—C2—C7−0.87 (17)C7—C2—C3—C40.1 (2)
C1—C8—C9—C10−107.09 (17)C7—C8—C9—C1073.94 (19)
C2—N1—C1—C80.5 (2)C8—C9—C10—N2−77.85 (16)
C2—C3—C4—C5−1.2 (2)C10—N2—C11—C12174.61 (13)
C2—C7—C8—C1−0.65 (15)C11—N2—C10—C9−101.41 (15)
C2—C7—C8—C9178.47 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···N21.01 (1)1.59 (1)2.5905 (15)175 (2)
N1—H1A···O1i0.87 (1)2.06 (1)2.9347 (16)177 (2)
N2—H2···O1ii0.90 (1)2.62 (1)3.4957 (17)166 (2)
Symmetry codes: (i) x−1/2, −y+3/2, z−1/2; (ii) −x+1, −y+1, −z+1.
 

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).

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Volume 82| Part 9| September 2026| Pages 1082-1086
https://doi.org/10.1107/S2056989026008571