Methyl 4-benz­yloxy-7-meth­oxy-1-methyl-1H-indole-2-carboxyl­ate

Peng Wang; Hualu Xing; Yang Liu; Wencheng Xie; Guisen Zhao

doi:10.1107/S1600536812031236

. 2012 Jul 18;68(Pt 8):o2480. doi: 10.1107/S1600536812031236

Methyl 4-benzyloxy-7-methoxy-1-methyl-1H-indole-2-carboxylate

Peng Wang ^a, Hualu Xing ^a, Yang Liu ^a, Wencheng Xie ^a, Guisen Zhao ^a,^*

PMCID: PMC3414935 PMID: 22904922

Abstract

There are two independent molecules in the asymmetric unit of the title compound, C₁₉H₁₉NO₄. The indole unit in each molecule is essentially planar, with mean deviations of 0.017 (1) and 0.013 (1) Å and forms dihedral angles of 50.17 (7) and 26.05 (6)° with the phenyl ring. In the crystal, molecules are linked by weak C–H⋯π interactions.

Related literature

For the antitumor activity of substituted indole compounds, see: Ziedan et al. (2010 ▶). For the crystal structures of related compounds, see: Butcher et al. (2006 ▶, 2007 ▶); Harrison et al. (2006 ▶); Hu et al. (2005 ▶). For the synthesis of 5-benzyloxy-7-bromo-1H-indole-2-carboxylic acid, see: Fresneda et al.(2001 ▶).

Experimental

Crystal data

C₁₉H₁₉NO₄
M _r = 325.35
Triclinic,
a = 7.622 (2) Å
b = 12.871 (4) Å
c = 16.928 (5) Å
α = 93.831 (3)°
β = 100.158 (3)°
γ = 93.456 (3)°
V = 1626.6 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.38 × 0.36 × 0.25 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.965, T _max = 0.977
19234 measured reflections
7421 independent reflections
5286 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.134
S = 1.05
7421 reflections
440 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2008 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812031236/lx2234sup1.cif

e-68-o2480-sup1.cif^{(40KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812031236/lx2234Isup2.hkl

e-68-o2480-Isup2.hkl^{(363.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812031236/lx2234Isup3.cml

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

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

Cg1, Cg2, Cg3 and Cg4 are the centroids of the C20–C25 phenyl, C1–C6 phenyl, C27–C32 phenyl and C12–C15/N1 pyrrole rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯Cg1	0.93	2.88	3.6778 (7)	145
C16—H16A⋯Cg2ⁱ	0.96	2.87	3.7812 (9)	158
C17—H17C⋯Cg3ⁱⁱ	0.96	2.90	3.845 (1)	167
C26—H26A⋯Cg4ⁱⁱⁱ	0.96	2.94	3.7442 (8)	141

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

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant No. 21072115) and Shandong Natural Science Foundation (grant No. ZR2011HM042).

supplementary crystallographic information

Comment

Substituted indole derivatives have attracted much attention due to their biological properties such as antitumor activities (Ziedan et al. 2010). Recently, the crystal structures of methyl 5-halo-1H-indole-2-carboxylate analogues were reported (Butcher et al., 2006, 2007; Harrison et al., 2006). We report herein the crystal structure of the title compound.

The asymmetric unit of the title compound is shown in Fig. 1. There are two independent unique molecules [labelled A & B] in which the indole unit is essentially planar, with mean deviations of 0.017 (1) Å for A and 0.013 (1) Å for B, respectively, from the least-squares plane defined by the nine constituent atoms. The crystal packing is stabilized by weak intermolecular C–H···π interactions (Table 1 & Fig. 2, Cg1, Cg2, Cg3 and Cg4 are the centroids of C20-C25 pheny ring, C1-C6 pheny ring, C27-C32 pheny ring and C12-C15/N1 pyrrol ring, respectively.

Experimental

A mixture of 4-(benzyloxy)-7-bromo-1H-indole-2-carboxylic acid (Fresneda et al., 2001) (0.35 g, 1 mmol), CuI (0.19 g, 1 mmol), CH₃ONa (0.38 g, 7 mmol) in anhydrous CH₃OH (2 ml) and DMF (4 ml) under N₂ atmosphere was heated to reflux for 5 h. After cooling to r.t., the mixture was poured into water (50 ml) and acidified with aq. HCl (6 N) to pH 1-2. The precipitate was filtered, washed several times with water, dried under vacuum, and then dissolved in anhydrous DMF. NaH (0.04 g, 1.5 mmol) was added to the solution under 0 ^oC followed by dimethyl sulfate (0.19 g, 1.5 mmol). The mixture was stired at r.t. for 4 h, and then was poured into ice-cold water. The precipitate was filtered, washed several times with water, and further purified by column chromatography (10% EtOAc/ Petroleum ether) and recrystallization from 10% EtOAc/Petroleum ether gave 0.21 g (64%) of white crystals. Crystals of X-ray diffraction quality were obtained by recrystallization from CH₂Cl₂/n-hexane mixture (4:1).