organic compounds
Z)-ethyl 3-[2-(5-methyl-7-nitro-1H-indole-2-carbonyl)hydrazinylidene]butanoate
of (aLaboratoire de chimie bioorganique, Faculté des Sciences, Université Chouaib Doukkali, BP 20, M-24000 El Jadida, Morocco, bLaboratoire de Chimie de Coordination et d'Analytique (LCCA), Faculté des Sciences, Université Chouaib Doukkali, BP 20, M-24000 El Jadida, Morocco, and cLaboratoire de Chimie du Solide Appliquée, Faculté des Sciences, Université Mohammed V, Avenue Ibn Battouta, BP 1014, Rabat, Morocco
*Correspondence e-mail: salaheddine_guesmi@yahoo.fr
The reaction of 5-methyl-7-nitro-1H-indole-2-carbohydrazide with ethyl acetoacetate yielded the title molecule, C16H18N4O5, in which the indole ring is almost planar, with the greatest deviation from the mean plane being 0.006 (2) Å. The nine atoms of the indole ring are almost perpendicular to the mean plane through the ethyl acetate group, as indicated by the dihedral angle of 87.02 (4)° between them. In the crystal, centrosymmetric supramolecular dimers are formed via N—H⋯O hydrogen bonds and eight-membered amide {⋯HNCO}2 synthons. These are consolidated into a three-dimensional architecture by C—H⋯O contacts, and by π–π interactions between six-membered rings [inter-centroid distance = 3.499 (2) Å].
Keywords: crystal structure; conformation; hydrogen bonding.
CCDC reference: 1418363
1. Related literature
For biochemical properties of indoles, see: Kuethe et al. (2005); Smith et al. (1998). For medicinal activity, see: El Kihel et al. (2007, 2013); Penning et al. (1997); Dumas et al. (2000). For starting materials, see: El Ouar et al. (1995).
2. Experimental
2.1. Crystal data
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2.3. Refinement
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Data collection: APEX2 (Bruker, 2009); cell SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).
Supporting information
CCDC reference: 1418363
https://doi.org/10.1107/S2056989015015054/tk5378sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015015054/tk5378Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989015015054/tk5378Isup3.cml
The ethyl 3-(2-(5-methyl-7-nitro-1H-indole-2-cabonyl)hydrazono)butanoate was synthesized from a mixture of 5-methyl-7-nitroindole-2-carbohydrazide (4.6 mmol) and ethyl acetoacetate (35 mmol) in ethanol which was heated on a steam bath at 353 K until dissolution. The mixture was kept at this temperature for 4 h. The crude product was filtered and crystallized from ethanol. Yellow crystals appeared after two weeks. The crystals were washed with cold ethanol and dried in air at room temperature.
The H atoms were located in a difference map and treated as riding with C—H = 0.93 Å (aromatic), C—H = 0.97 Å (methylene) and C—H = 0.96 Å (methyl), and with Uiso(H) = 1.2 Ueq (aromatic and methylene) and Uiso(H) = 1.5 Ueq (methyl).
The indole nucleus is probably the most widely distributed heterocyclic ring system found in nature (Kuethe et al., 2005). Due to the existence of a vast array of structurally diverse and biologically active indoles, it is not surprising that the indole nucleus is an important feature in many medicinal agents and the most important of all structural classes in drug discovery (Smith et al., 1998). For example, the identification of new and selective cox-2 inhibitors (Penning et al., 1997), for the relief of pain, and the treatment of the symptoms of arthritis and related diseases has been an important advance in modern anti-inflammatory therapy. In a related area, heterocycle-appended pyrazoles have been reported (Dumas et al., 2000) to be potent and selective as inhibitors of the mitogen-activated protein kinase p38 and consequently provide a novel approach for the treatment of rheumatoid arthritis and related inflammatory diseases. The synthesis and reactivity of indole derivatives have been a topic of research interest for well over a century. Due to the potent biological activity exhibited by various indoles derivatives, there is a continuous demand for novel synthetic procedures in this area. In previous papers (El Kihel et al., 2007; 2013; El Ouar et al., 1995), we have reported some reactions of 7-aminoindoles and the condensation of the 7-nitroindole-2-carbohydrazide with acetylacetone. Herein, we report the synthesis of an open intermediate, 5-methyl-7-nitroindole-2-carbohydrazide, by condensation with ethyl acetoacetate.
The fused five- and six-membered rings, part of the title compound, are essentially planar with the largest deviation from the mean plane being 0.006 (2) Å at C1 atom as shown in Fig. 1. The mean plane through the ethyl acetate group is virtually perpendicular to the indasol ring as indicated by the dihedral angle of 87.02 (4) ° between them. The cohesion of the crystal is ensured by C—H···O and N—H···O hydrogen bonds, and by π—π interactions between phenyl rings [intercentroid distance = 3.499 (2) Å], as shown in Fig. 2 and Table 2.
For biochemical properties of indoles, see: Kuethe et al. (2005); Smith et al. (1998). For medicinal activity, see: El Kihel et al. (2007); El Kihel et al. (2013_; Penning et al. (1997); Dumas et al. (2000). For starting materials, see: El Ouar et al. (1995).
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).Fig. 1. Plot of the molecule with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. | |
Fig. 2. A view of the crystal packing of the title compound, showing intermolecular π—π interactions between six-membered rings (dashed green lines) and intermolecular hydrogen bonds (dashed blue lines). |
C16H18N4O5 | Z = 2 |
Mr = 346.34 | F(000) = 364 |
Triclinic, P1 | Dx = 1.363 Mg m−3 |
a = 8.4716 (9) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 8.4722 (7) Å | Cell parameters from 3676 reflections |
c = 13.0971 (9) Å | θ = 2.5–27.1° |
α = 108.695 (4)° | µ = 0.10 mm−1 |
β = 91.865 (4)° | T = 296 K |
γ = 106.886 (4)° | Block, yellow |
V = 843.80 (13) Å3 | 0.35 × 0.30 × 0.27 mm |
Bruker X8 APEX diffractometer | 3676 independent reflections |
Radiation source: fine-focus sealed tube | 3120 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.033 |
φ and ω scans | θmax = 27.1°, θmin = 2.5° |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | h = −10→10 |
Tmin = 0.589, Tmax = 0.746 | k = −10→10 |
18286 measured reflections | l = −16→16 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.043 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.124 | H-atom parameters constrained |
S = 1.07 | w = 1/[σ2(Fo2) + (0.059P)2 + 0.3197P] where P = (Fo2 + 2Fc2)/3 |
3676 reflections | (Δ/σ)max < 0.001 |
226 parameters | Δρmax = 0.30 e Å−3 |
0 restraints | Δρmin = −0.24 e Å−3 |
C16H18N4O5 | γ = 106.886 (4)° |
Mr = 346.34 | V = 843.80 (13) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.4716 (9) Å | Mo Kα radiation |
b = 8.4722 (7) Å | µ = 0.10 mm−1 |
c = 13.0971 (9) Å | T = 296 K |
α = 108.695 (4)° | 0.35 × 0.30 × 0.27 mm |
β = 91.865 (4)° |
Bruker X8 APEX diffractometer | 3676 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | 3120 reflections with I > 2σ(I) |
Tmin = 0.589, Tmax = 0.746 | Rint = 0.033 |
18286 measured reflections |
R[F2 > 2σ(F2)] = 0.043 | 0 restraints |
wR(F2) = 0.124 | H-atom parameters constrained |
S = 1.07 | Δρmax = 0.30 e Å−3 |
3676 reflections | Δρmin = −0.24 e Å−3 |
226 parameters |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against all reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on all data will be even larger. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.17198 (16) | 0.64599 (17) | 0.94250 (11) | 0.0241 (3) | |
C2 | 0.12573 (17) | 0.78350 (18) | 1.00943 (12) | 0.0266 (3) | |
H2 | 0.0884 | 0.8540 | 0.9793 | 0.032* | |
C3 | 0.13423 (17) | 0.81836 (18) | 1.12214 (12) | 0.0272 (3) | |
C4 | 0.18973 (17) | 0.71346 (18) | 1.16710 (11) | 0.0265 (3) | |
H4 | 0.1948 | 0.7356 | 1.2416 | 0.032* | |
C5 | 0.23851 (16) | 0.57373 (17) | 1.10067 (10) | 0.0233 (3) | |
C6 | 0.22965 (16) | 0.54061 (16) | 0.98701 (10) | 0.0215 (3) | |
C7 | 0.0821 (2) | 0.9697 (2) | 1.19212 (14) | 0.0366 (4) | |
H7A | 0.1600 | 1.0786 | 1.1935 | 0.055* | |
H7B | 0.0803 | 0.9670 | 1.2648 | 0.055* | |
H7C | −0.0270 | 0.9596 | 1.1625 | 0.055* | |
C8 | 0.30024 (17) | 0.44531 (18) | 1.12041 (11) | 0.0250 (3) | |
H8 | 0.3193 | 0.4334 | 1.1875 | 0.030* | |
C9 | 0.32627 (16) | 0.34231 (17) | 1.02184 (11) | 0.0228 (3) | |
C10 | 0.39564 (16) | 0.19582 (17) | 1.00510 (10) | 0.0227 (3) | |
C11 | 0.39038 (17) | 0.03684 (19) | 0.72021 (11) | 0.0264 (3) | |
C12 | 0.4537 (2) | −0.1170 (2) | 0.69488 (12) | 0.0343 (3) | |
H12A | 0.5004 | −0.1320 | 0.6280 | 0.052* | |
H12B | 0.3634 | −0.2211 | 0.6877 | 0.052* | |
H12C | 0.5378 | −0.0967 | 0.7527 | 0.052* | |
C13 | 0.3494 (2) | 0.0920 (2) | 0.62686 (12) | 0.0360 (4) | |
H13A | 0.4517 | 0.1398 | 0.6004 | 0.043* | |
H13B | 0.2990 | 0.1842 | 0.6527 | 0.043* | |
C14 | 0.2322 (2) | −0.0586 (2) | 0.53418 (12) | 0.0394 (4) | |
C15 | −0.0299 (2) | −0.2793 (3) | 0.48056 (15) | 0.0516 (5) | |
H15A | 0.0177 | −0.3734 | 0.4529 | 0.062* | |
H15B | −0.0586 | −0.2445 | 0.4206 | 0.062* | |
C16 | −0.1808 (3) | −0.3393 (3) | 0.5309 (2) | 0.0656 (6) | |
H16A | −0.2618 | −0.4381 | 0.4773 | 0.098* | |
H16B | −0.2271 | −0.2453 | 0.5575 | 0.098* | |
H16C | −0.1508 | −0.3731 | 0.5901 | 0.098* | |
N1 | 0.15863 (16) | 0.61115 (16) | 0.82643 (10) | 0.0296 (3) | |
N2 | 0.28297 (14) | 0.40043 (14) | 0.94143 (9) | 0.0223 (2) | |
H2N | 0.2888 | 0.3552 | 0.8733 | 0.027* | |
N3 | 0.41081 (15) | 0.09582 (15) | 0.90428 (9) | 0.0247 (3) | |
H3N | 0.4466 | 0.0082 | 0.8968 | 0.030* | |
N4 | 0.36975 (14) | 0.13223 (15) | 0.81339 (9) | 0.0251 (3) | |
O1 | 0.10064 (17) | 0.70060 (17) | 0.78835 (10) | 0.0465 (3) | |
O2 | 0.20654 (16) | 0.49110 (15) | 0.76987 (8) | 0.0386 (3) | |
O3 | 0.43926 (13) | 0.16440 (13) | 1.08520 (8) | 0.0298 (2) | |
O4 | 0.2639 (2) | −0.1084 (3) | 0.44345 (11) | 0.0763 (5) | |
O5 | 0.08886 (16) | −0.13058 (17) | 0.56453 (9) | 0.0447 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0223 (6) | 0.0229 (6) | 0.0240 (6) | 0.0050 (5) | 0.0025 (5) | 0.0060 (5) |
C2 | 0.0232 (7) | 0.0218 (6) | 0.0336 (7) | 0.0075 (5) | 0.0029 (5) | 0.0079 (5) |
C3 | 0.0228 (7) | 0.0218 (6) | 0.0312 (7) | 0.0062 (5) | 0.0048 (5) | 0.0023 (5) |
C4 | 0.0260 (7) | 0.0256 (7) | 0.0225 (6) | 0.0069 (5) | 0.0047 (5) | 0.0023 (5) |
C5 | 0.0216 (6) | 0.0228 (6) | 0.0216 (6) | 0.0055 (5) | 0.0030 (5) | 0.0039 (5) |
C6 | 0.0195 (6) | 0.0201 (6) | 0.0215 (6) | 0.0053 (5) | 0.0033 (5) | 0.0037 (5) |
C7 | 0.0363 (8) | 0.0299 (8) | 0.0398 (8) | 0.0162 (6) | 0.0074 (7) | 0.0017 (6) |
C8 | 0.0258 (7) | 0.0269 (7) | 0.0211 (6) | 0.0082 (5) | 0.0035 (5) | 0.0067 (5) |
C9 | 0.0213 (6) | 0.0224 (6) | 0.0229 (6) | 0.0066 (5) | 0.0026 (5) | 0.0057 (5) |
C10 | 0.0217 (6) | 0.0227 (6) | 0.0223 (6) | 0.0067 (5) | 0.0035 (5) | 0.0061 (5) |
C11 | 0.0244 (7) | 0.0314 (7) | 0.0218 (6) | 0.0104 (6) | 0.0030 (5) | 0.0060 (5) |
C12 | 0.0435 (9) | 0.0382 (8) | 0.0241 (7) | 0.0221 (7) | 0.0063 (6) | 0.0061 (6) |
C13 | 0.0445 (9) | 0.0442 (9) | 0.0261 (7) | 0.0230 (7) | 0.0069 (6) | 0.0126 (6) |
C14 | 0.0464 (10) | 0.0562 (10) | 0.0224 (7) | 0.0294 (8) | 0.0039 (6) | 0.0107 (7) |
C15 | 0.0524 (11) | 0.0524 (11) | 0.0374 (9) | 0.0216 (9) | −0.0083 (8) | −0.0040 (8) |
C16 | 0.0566 (13) | 0.0561 (12) | 0.0642 (14) | 0.0105 (10) | −0.0010 (10) | 0.0021 (11) |
N1 | 0.0331 (7) | 0.0295 (6) | 0.0266 (6) | 0.0106 (5) | 0.0026 (5) | 0.0098 (5) |
N2 | 0.0246 (6) | 0.0223 (5) | 0.0190 (5) | 0.0090 (4) | 0.0039 (4) | 0.0042 (4) |
N3 | 0.0292 (6) | 0.0250 (6) | 0.0219 (6) | 0.0137 (5) | 0.0035 (5) | 0.0063 (5) |
N4 | 0.0253 (6) | 0.0290 (6) | 0.0208 (5) | 0.0110 (5) | 0.0022 (4) | 0.0064 (5) |
O1 | 0.0654 (8) | 0.0529 (7) | 0.0374 (6) | 0.0334 (7) | 0.0064 (6) | 0.0237 (6) |
O2 | 0.0557 (7) | 0.0387 (6) | 0.0236 (5) | 0.0232 (5) | 0.0058 (5) | 0.0062 (5) |
O3 | 0.0398 (6) | 0.0314 (5) | 0.0231 (5) | 0.0184 (5) | 0.0058 (4) | 0.0094 (4) |
O4 | 0.0659 (10) | 0.1143 (14) | 0.0251 (6) | 0.0216 (9) | 0.0100 (6) | −0.0011 (7) |
O5 | 0.0476 (7) | 0.0525 (7) | 0.0261 (5) | 0.0178 (6) | 0.0013 (5) | 0.0019 (5) |
C1—C2 | 1.3827 (19) | C11—C12 | 1.496 (2) |
C1—C6 | 1.3943 (19) | C11—C13 | 1.505 (2) |
C1—N1 | 1.4465 (18) | C12—H12A | 0.9600 |
C2—C3 | 1.404 (2) | C12—H12B | 0.9600 |
C2—H2 | 0.9300 | C12—H12C | 0.9600 |
C3—C4 | 1.385 (2) | C13—C14 | 1.510 (2) |
C3—C7 | 1.5100 (19) | C13—H13A | 0.9700 |
C4—C5 | 1.4059 (18) | C13—H13B | 0.9700 |
C4—H4 | 0.9300 | C14—O4 | 1.195 (2) |
C5—C6 | 1.4188 (18) | C14—O5 | 1.327 (2) |
C5—C8 | 1.4234 (19) | C15—O5 | 1.453 (2) |
C6—N2 | 1.3585 (16) | C15—C16 | 1.490 (3) |
C7—H7A | 0.9600 | C15—H15A | 0.9700 |
C7—H7B | 0.9600 | C15—H15B | 0.9700 |
C7—H7C | 0.9600 | C16—H16A | 0.9600 |
C8—C9 | 1.3729 (18) | C16—H16B | 0.9600 |
C8—H8 | 0.9300 | C16—H16C | 0.9600 |
C9—N2 | 1.3778 (17) | N1—O1 | 1.2276 (17) |
C9—C10 | 1.4803 (19) | N1—O2 | 1.2347 (16) |
C10—O3 | 1.2325 (16) | N2—H2N | 0.8600 |
C10—N3 | 1.3547 (17) | N3—N4 | 1.3798 (16) |
C11—N4 | 1.2793 (17) | N3—H3N | 0.8600 |
C2—C1—C6 | 119.89 (13) | C11—C12—H12B | 109.5 |
C2—C1—N1 | 119.77 (13) | H12A—C12—H12B | 109.5 |
C6—C1—N1 | 120.34 (12) | C11—C12—H12C | 109.5 |
C1—C2—C3 | 121.06 (13) | H12A—C12—H12C | 109.5 |
C1—C2—H2 | 119.5 | H12B—C12—H12C | 109.5 |
C3—C2—H2 | 119.5 | C11—C13—C14 | 112.44 (13) |
C4—C3—C2 | 119.56 (12) | C11—C13—H13A | 109.1 |
C4—C3—C7 | 121.18 (13) | C14—C13—H13A | 109.1 |
C2—C3—C7 | 119.26 (14) | C11—C13—H13B | 109.1 |
C3—C4—C5 | 120.34 (13) | C14—C13—H13B | 109.1 |
C3—C4—H4 | 119.8 | H13A—C13—H13B | 107.8 |
C5—C4—H4 | 119.8 | O4—C14—O5 | 123.36 (17) |
C4—C5—C6 | 119.39 (13) | O4—C14—C13 | 124.16 (18) |
C4—C5—C8 | 134.22 (13) | O5—C14—C13 | 112.47 (13) |
C6—C5—C8 | 106.39 (11) | O5—C15—C16 | 107.43 (15) |
N2—C6—C1 | 132.14 (12) | O5—C15—H15A | 110.2 |
N2—C6—C5 | 108.10 (12) | C16—C15—H15A | 110.2 |
C1—C6—C5 | 119.76 (12) | O5—C15—H15B | 110.2 |
C3—C7—H7A | 109.5 | C16—C15—H15B | 110.2 |
C3—C7—H7B | 109.5 | H15A—C15—H15B | 108.5 |
H7A—C7—H7B | 109.5 | C15—C16—H16A | 109.5 |
C3—C7—H7C | 109.5 | C15—C16—H16B | 109.5 |
H7A—C7—H7C | 109.5 | H16A—C16—H16B | 109.5 |
H7B—C7—H7C | 109.5 | C15—C16—H16C | 109.5 |
C9—C8—C5 | 107.13 (12) | H16A—C16—H16C | 109.5 |
C9—C8—H8 | 126.4 | H16B—C16—H16C | 109.5 |
C5—C8—H8 | 126.4 | O1—N1—O2 | 122.89 (13) |
C8—C9—N2 | 109.32 (12) | O1—N1—C1 | 119.29 (12) |
C8—C9—C10 | 125.34 (12) | O2—N1—C1 | 117.82 (12) |
N2—C9—C10 | 125.31 (12) | C6—N2—C9 | 109.07 (11) |
O3—C10—N3 | 119.72 (12) | C6—N2—H2N | 125.5 |
O3—C10—C9 | 118.74 (12) | C9—N2—H2N | 125.5 |
N3—C10—C9 | 121.53 (12) | C10—N3—N4 | 121.12 (11) |
N4—C11—C12 | 127.75 (13) | C10—N3—H3N | 119.4 |
N4—C11—C13 | 114.81 (13) | N4—N3—H3N | 119.4 |
C12—C11—C13 | 117.42 (12) | C11—N4—N3 | 118.81 (12) |
C11—C12—H12A | 109.5 | C14—O5—C15 | 115.98 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O3i | 0.86 | 2.04 | 2.8815 (15) | 167 |
C12—H12C···O3i | 0.96 | 2.39 | 3.1723 (18) | 139 |
C4—H4···O4ii | 0.93 | 2.51 | 3.4019 (19) | 161 |
C13—H13A···O4iii | 0.97 | 2.56 | 3.407 (2) | 146 |
Symmetry codes: (i) −x+1, −y, −z+2; (ii) x, y+1, z+1; (iii) −x+1, −y, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
N3—H3N···O3i | 0.86 | 2.04 | 2.8815 (15) | 167 |
C12—H12C···O3i | 0.96 | 2.39 | 3.1723 (18) | 139 |
C4—H4···O4ii | 0.93 | 2.51 | 3.4019 (19) | 161 |
C13—H13A···O4iii | 0.97 | 2.56 | 3.407 (2) | 146 |
Symmetry codes: (i) −x+1, −y, −z+2; (ii) x, y+1, z+1; (iii) −x+1, −y, −z+1. |
Acknowledgements
The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements, and Chouaib Doukkali University, El Jadida, Morocco, for financial support.
References
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The indole nucleus is probably the most widely distributed heterocyclic ring system found in nature (Kuethe et al., 2005). Due to the existence of a vast array of structurally diverse and biologically active indoles, it is not surprising that the indole nucleus is an important feature in many medicinal agents and the most important of all structural classes in drug discovery (Smith et al., 1998). For example, the identification of new and selective cox-2 inhibitors (Penning et al., 1997), for the relief of pain, and the treatment of the symptoms of arthritis and related diseases has been an important advance in modern anti-inflammatory therapy. In a related area, heterocycle-appended pyrazoles have been reported (Dumas et al., 2000) to be potent and selective as inhibitors of the mitogen-activated protein kinase p38 and consequently provide a novel approach for the treatment of rheumatoid arthritis and related inflammatory diseases. The synthesis and reactivity of indole derivatives have been a topic of research interest for well over a century. Due to the potent biological activity exhibited by various indoles derivatives, there is a continuous demand for novel synthetic procedures in this area. In previous papers (El Kihel et al., 2007; 2013; El Ouar et al., 1995), we have reported some reactions of 7-aminoindoles and the condensation of the 7-nitroindole-2-carbohydrazide with acetylacetone. Herein, we report the synthesis of an open intermediate, 5-methyl-7-nitroindole-2-carbohydrazide, by condensation with ethyl acetoacetate.
The fused five- and six-membered rings, part of the title compound, are essentially planar with the largest deviation from the mean plane being 0.006 (2) Å at C1 atom as shown in Fig. 1. The mean plane through the ethyl acetate group is virtually perpendicular to the indasol ring as indicated by the dihedral angle of 87.02 (4) ° between them. The cohesion of the crystal is ensured by C—H···O and N—H···O hydrogen bonds, and by π—π interactions between phenyl rings [intercentroid distance = 3.499 (2) Å], as shown in Fig. 2 and Table 2.