Methyl 3-(1H-indole-3-carboxamido)propionate hemihydrate

Gang Huang; Xing Yan Xu; Xiang Chao Zeng; Le Zheng; Kai Ping Li

doi:10.1107/S1600536810018015

. 2010 May 26;66(Pt 6):o1472. doi: 10.1107/S1600536810018015

Methyl 3-(1H-indole-3-carboxamido)propionate hemihydrate

Gang Huang ^a, Xing Yan Xu ^a, Xiang Chao Zeng ^a,^*, Le Zheng ^a, Kai Ping Li ^a

PMCID: PMC2979597 PMID: 21579540

Abstract

The title compound, C₁₃H₁₄N₂O₃·0.5H₂O, was synthesized by the condensation of methyl 3-aminopropionate with 3-trichloroacetylindole. The two organic molecules in the asymmetric unit are both close to planar, with r.m.s. deviations from the best fit plane through all of the non-H atoms of 0.004 (2) Å for molecule A and 0.006 (1) Å for molecule B. Also, the five- and six-membered rings of the indole systems are inclined at 1.67 (8) and 1.50 (8)° in molecules A and B, respectively. In the crystal structure, the organic molecules are connected by intermolecular N—H⋯O hydrogen bonds, forming chains. O—H⋯O and N—H⋯O hydrogen-bond interactions involving the water molecules interlink these chains, forming double chains approximately parallel to the a axis.

Related literature

For the bioactivity of indole derivatives, see: Fabio et al. (2007 ▶); Sharma et al. (2004 ▶). For related structures, see: Huang et al. (2009 ▶); Siddiquee et al. (2009 ▶). For reference structural data, see Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₃H₁₄N₂O₃·0.5H₂O
M _r = 255.27
Monoclinic,
a = 10.8220 (13) Å
b = 9.7668 (12) Å
c = 23.623 (3) Å
β = 92.422 (2)°
V = 2494.6 (5) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 173 K
0.46 × 0.43 × 0.39 mm

Data collection

Bruker SMART 1K CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.955, T _max = 0.962
13021 measured reflections
5484 independent reflections
4349 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.126
S = 1.07
5484 reflections
336 parameters
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: SMART (Bruker, 1999 ▶); cell refinement: SAINT-Plus (Bruker, 1999 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810018015/sj2794sup1.cif

e-66-o1472-sup1.cif^{(24.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810018015/sj2794Isup2.hkl

e-66-o1472-Isup2.hkl^{(268.5KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O4ⁱ	0.88	2.04	2.8219 (15)	148
N2—H2⋯O1Wⁱⁱ	0.88	2.09	2.9348 (17)	161
N3—H3⋯O1	0.88	1.88	2.7404 (16)	164
N4—H4A⋯O2	0.88	2.43	3.2952 (15)	167
O1W—H1B⋯O4	0.85	2.17	2.9890 (18)	161
O1W—H1C⋯O5ⁱⁱⁱ	0.85	1.98	2.7970 (16)	160

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

We thank the Natural Science Foundation of Guangdong Province, China (No. 06300581) for generously supporting this study.

supplementary crystallographic information

Comment

Many indole derivatives show important bioactivity, acting as metabotropic receptor antagonists (Fabio et al., 2007) and showing protein kinase inhibiting activity (Sharma et al., 2004). This is the reason they have attracted our interest and the title compound is related to our previous structural investigations of methyl 3-(1-Butyl-1H-indole-3-carbonyl)aminopropionate (Huang et al., 2009).

The asymmetric unit of the title compound comprises two substituted indole molecules, A & B and a solvent water molecule, Fig. 1. The organic molecules are each reasonably planar with rms deviations from the best fit plane through all of the non hydrogen atoms of 0.004 (2) Å for A and -0.006 (1) Å for B. Also the five and six-membered rings of the indole systems are inclined at 1.67 (8) ° and 1.50 (8) ° in A and B respectively. Bond lengths in both molecules are unexceptional (Allen et al., 1987) and are comparable to those found in similar structures (Huang et al., 2009; Siddiquee et al., 2009).

In the crystal structure, molecules of the organic compound are linked through N—H···O H-bonds to form dimers that are connected by another N—H···O H-bonds to generate chains, and the O—H(W)···O and N—H···O(W) H-bond interactions link these chains to form double-chains extending to the a axis (Table 1, Fig. 2).

Experimental

The hydrochloride salt of methyl 3-aminopropionate (0.70 g, 5 mmol) and 3-trichloroacetylindole (1.32 g, 5 mmol) were added to acetonitrile (10 ml), followed by the dropwise addition of triethylamine (1.2 ml). The mixture was stirred at room temperature for 16 h and then poured into water. After filtration, the precipitate was collected as a yellow solid. The impure product was dissolved in EtOH at room temperature. Light yellow monoclinic crystals suitable for X-ray analysis (m.p. 409 K, 86.2% yield) grew over a period of one week when the solution was exposed to the air.