1-[(3,5-Dimethyl-1H-pyrazol-1-yl)carbon­yl]-5-methyl­indolizine-3-carbo­nitrile

Wei-Jin Gu; Wen-Li Xie; Ting-Ting Wang

doi:10.1107/S1600536812046727

. 2012 Nov 24;68(Pt 12):o3399. doi: 10.1107/S1600536812046727

1-[(3,5-Dimethyl-1H-pyrazol-1-yl)carbonyl]-5-methylindolizine-3-carbonitrile

Wei-Jin Gu ^a,^b,^*, Wen-Li Xie ^a, Ting-Ting Wang ^a

PMCID: PMC3588990 PMID: 23476226

Abstract

In the title molecule, C₁₆H₁₄N₄O, the indolizine ring system is essentially planar, with a maximum deviation of 0.013 (3) Å, and forms a dihedral angle of 7.52 (12)° with the pyrazole ring. In the crystal, weak C—H⋯O hydrogen bonds and π–π stacking interactions, with a centroid–centroid distance of 3.6378 (16) Å, link molecules along [001].

Related literature

For biological applications of indolizines and pyrazoles, see: Tukulula et al. (2010 ▶); James et al. (2008 ▶); Teklu et al. (2005 ▶); McDonald et al. (2006 ▶); Jagerovic et al. (2002 ▶). For background and the synthesis of related hetrocycles, see: Gu et al. (2011 ▶); Shen et al. (2006 ▶, 2008 ▶); Wang, et al. (2000 ▶).

Experimental

Crystal data

C₁₆H₁₄N₄O
M _r = 278.31
Monoclinic,
a = 8.5911 (18) Å
b = 23.3760 (15) Å
c = 7.5816 (12) Å
β = 114.775 (3)°
V = 1382.4 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 291 K
0.30 × 0.25 × 0.20 mm

Data collection

Bruker SMART APEX diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ▶) T _min = 0.974, T _max = 0.983
7822 measured reflections
2361 independent reflections
1728 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.135
S = 1.05
2361 reflections
194 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Click here for additional data file.^{(18.6KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812046727/lh5554sup1.cif

e-68-o3399-sup1.cif^{(18.6KB, cif)}

Click here for additional data file.^{(116KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812046727/lh5554Isup2.hkl

e-68-o3399-Isup2.hkl^{(116KB, hkl)}

Click here for additional data file.^{(5.7KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812046727/lh5554Isup3.cml

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
C10—H10B⋯O1ⁱ	0.96	2.56	3.435 (4)	151

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for financial support.

supplementary crystallographic information

Comment

Indolizines and pyrazoles are important classes of bio-active drug targets in the pharmaceutical industry, as they are the core structure of numerous biologically active compounds (Tukulula et al., 2010; James et al., 2008; Teklu et al., 2005; McDonald et al., 2006; Jagerovic et al., 2002). In our continuing studies on the synthesis and properties of heterocycles (Gu et al., 2011; Shen et al., 2008; Shen et al., 2006; Wang, et al., 2000) we have prepared (Fig. 1) and determined the crystal structure of the title compound.

The molecular structure of the title compound is shown in Fig. 2. The indolizine ring system is essentially planar with a maximum deviation for atom C3 of 0.013 (3)Å. The dihedral angle formed by the indolizine ring system and the pyrazole ring is 7.52 (12)°. In the crystal, weak C—H···O hydrogen bonds and π–π stacking interactions, with Cg1···Cg2ⁱ = 3.6378 (16)Å, link molecules along [001] (Fig. 3). Cg1 and Cg2 are the centroids of the N1/C5-C8 and N1/C1-C5 rings (symmetry code (i): x, 1/2-y, -1/2+z).

Experimental

Methyl-3-cyano-5-methylindolizine-1-carboxylate was prepared through 1,3-dipolar cycloaddition according to a procedure described in the literature (Wang, et al., 2000). A suspension of N-cyano-2-methylpyridinium bromide (C₅H₄N⁺CH₃CN.Br^-) (10 mmol), ethyl acrylate (40 mmol), Et₃N (20 ml) and CrO₃ (20 mmol) in DMF (40 ml) was stirred at 363K for 4 h (monitored by TLC). The mixture was cooled to room temperature and poured into 5% aqueous HCl (150 mL). The brown powder was collected by filtration and washed with ethanol (25 mL). After drying the solid was collected 1.28 g (60%).

Methyl-3-cyano-5-methylindolizine-1-carboxylate (5 mmol) was dissolved in 6 ml of ethanol and 20 ml 80% N₂H₄.H₂O (30 mmol) was added dropwise. The solution was refluxed for 6 h and cooled to yield the product, 0.87 g (81%) as 3-cyano-5-methylindolizine-1-carbohydrazide.

3-cyano-5-methylindolizine-1-carbohydrazide (1 mmol) was dissolved in 2 ml acetic acid, then acetylacetone (2 mmol, dissolved in 2ml ethanol) was added. After stirring for 2 h, the mixture was purified by chromatography [silica gel, 20% ethyl acetate in petroleum ether (60 C90)] to yield colorless block crystals of the title compound, 0.22 g (79%). 1H-NMR (CDCl₃, 400 MHz): 2.33 (s, 3H, –CH3), 2.65 (s, 3H, –CH3), 3.06 (s, 3H, –CH3), 6.06 (s, 1H, pyrazole =CH), 6.80 (d, 1H, indolizine =CH), 7.33 (t, 1H, indolizine =CH), 8.52 (d, 1H, indolizine =CH), 8.59 (s, 1H, indolizine =CH).