1-(2-Hy­droxy­eth­yl)-3-[(2-hy­droxy­eth­yl)amino]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

Zhi-Xiong Xie; Sheng-Yin Zhao

doi:10.1107/S1600536811007677

. 2011 Mar 12;67(Pt 4):o854. doi: 10.1107/S1600536811007677

1-(2-Hydroxyethyl)-3-[(2-hydroxyethyl)amino]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

Zhi-Xiong Xie ^a, Sheng-Yin Zhao ^a,^*

PMCID: PMC3099822 PMID: 21754135

Abstract

There are four molecules in the asymmetric unit of the title compound, C₁₆H₁₇N₃O₄, in which the dihedral angles between the indole ring system and maleimide ring are 4.5 (3), 8.3 (3), 8.4 (2) and 10.4 (2)°. In the crystal, molecules are linked by numerous N—H⋯O and O—H⋯O hydrogen bonds, generating a three-dimensional network.

Related literature

For general background to indolylmaleimides and their biological properties, see: Vegesna et al. (1998) ▶; Hu (1996 ▶); Zhao et al. (2008 ▶). For the preparation, see: Zhao et al. (2010 ▶).

Experimental

Crystal data

C₁₆H₁₇N₃O₄
M _r = 315.33
Triclinic,
a = 13.0276 (10) Å
b = 14.8150 (11) Å
c = 17.8893 (14) Å
α = 90.012 (1)°
β = 110.295 (2)°
γ = 102.187 (2)°
V = 3155.2 (4) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.43 × 0.33 × 0.27 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2003 ▶) T _min = 0.594, T _max = 1.000
17464 measured reflections
12193 independent reflections
6708 reflections with I > 2σ(I)
R _int = 0.035

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.098
S = 0.89
12193 reflections
893 parameters
13 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: SMART (Bruker, 2003 ▶); cell refinement: SAINT (Bruker, 2003 ▶); data reduction: SAINT; 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/S1600536811007677/hb5807sup1.cif

e-67-0o854-sup1.cif^{(47.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811007677/hb5807Isup2.hkl

e-67-0o854-Isup2.hkl^{(596.1KB, 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
N2—H2⋯O12ⁱ	0.86 (3)	2.09 (3)	2.950 (3)	177 (3)
O3—H3⋯O8ⁱⁱ	0.84 (3)	1.93 (3)	2.762 (3)	172 (3)
O4—H4⋯O14ⁱⁱⁱ	0.82 (2)	1.97 (2)	2.770 (2)	163 (3)
N5—H5⋯O16^iv	0.83 (2)	2.22 (2)	3.027 (3)	164 (2)
O7—H7⋯O4^v	0.86 (2)	1.89 (2)	2.755 (3)	175 (3)
O15—H15⋯O1^vi	0.84 (2)	2.22 (2)	2.893 (2)	137 (3)
O15—H15⋯O12^vii	0.84 (2)	2.42 (2)	3.097 (3)	139 (3)
O16—H16⋯O11ⁱ	0.83 (2)	1.96 (2)	2.780 (3)	170 (3)
N3—H3A⋯O6ⁱⁱⁱ	0.87 (2)	2.06 (2)	2.840 (2)	149 (2)
N6—H6A⋯O14	0.84 (2)	2.22 (2)	3.042 (3)	168 (2)
O8—H8A⋯O10^viii	0.85 (2)	1.90 (2)	2.746 (3)	173 (3)
N9—H9A⋯O2^viii	0.89 (2)	1.95 (2)	2.760 (2)	152 (2)
O11—H11A⋯O5ⁱⁱ	0.87 (2)	2.13 (2)	2.935 (2)	154 (3)
O11—H11A⋯O16	0.87 (2)	2.51 (3)	3.033 (3)	120 (3)
O12—H12A⋯O15^ix	0.84 (2)	1.92 (2)	2.739 (2)	168 (3)
N8—H8B⋯O7^x	0.89 (2)	2.09 (2)	2.867 (3)	146 (2)
N11—H11B⋯O3	0.88 (2)	2.17 (2)	2.945 (3)	147 (2)
N12—H12B⋯O10^viii	0.85 (2)	2.10 (2)	2.925 (2)	164 (2)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) ; (viii) ; (ix) ; (x) .

Acknowledgments

We thank the Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry of China (No. [2008]890) for financial support.

supplementary crystallographic information

Comment

The indolylmaleimides and their derivatives derived from staurosporine, is a specific class of protein kinase C inhibitors,and can be used to treat or prevent a variety of conditions and diseases,such as an inflammatory diseasea or some kinds of cancer disease and so on (Vegesna et al., 1998; Hu, 1996; Zhao et al., 2008). The pharmacological results showed that the title compound displayed potent cytotoxic activity. Our reserach group has focused on the synthesis of the indolylmaleimides and their derivatives and we now report the structure of the title compound, (I).

The X-ray structural analysis confirmed the assignment of its structure from spectroscopic data. The asymmetric unit of (I) contains four independent molecules, each molecules are linked to each other through N—H···O and O—H···O intermolecular hydrogen bonds(Table 1, Fig. 1).The four molecules show slightly different conformations: the dihedral angles between the indole ring and maleimide ring are 4.5 (3), 8.4 (2),10.4 (2) and 8.3 (3)° in the four independent molecules.

In the crystal (Fig. 2),indolylmaleimide molecules are linked by intermolecular N—H···O hydrogen bonds. The layers are further connected into a three-dimensional network by N—H···O and O—H···O hydrogen bonds involving the maleimide molecules as H-donors and by weak π–π stacking interactions involving neighbouring indole and maleimide rings.

Experimental

3-Bromo-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione (0.5 g, 1.67 mmol), 2-aminoethanol(0.15 g, 2.46 mmol) and 1.5 ml triethylamine was added to DMF (8 ml) in a flask. The reaction mixture was stirred at 363 K under argon for 10 h. After the completion of the reaction (determined by TLC), the reaction mixture was cooled to room temperature, and diluted with ethylacetate (80 ml). The solution was washed successively with water (50 ml), brine (50 ml) and then dried with anhydrous magnesium sulfate. The crude material was purified by chromatography with 2:1(hexane-EtOAc) as red crystals (0.31 g, 61%). The crystals were obtained by dissolving the title compound (0.3 g, 1.0 mmol) in ethyl acetate (5 ml) and ethanol (5 ml) and evaporating the solvent slowly at room temperature for about 2 d to yield red blocks.