key: cord-0919869-h45zlv8f
authors: Gündüz, Miyase Gözde; Butcher, Ray J.; Öztürk Yildirim, Sema; El-Khouly, Ahmed; Şafak, Cihat; Şimşek, Rahime
title: Ethyl 4-(5-bromo-1H-indol-3-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carboxyl­ate
date: 2012-11-24
journal: Acta Crystallogr Sect E Struct Rep Online
DOI: 10.1107/s1600536812046909
sha: 757d0a46fdff943b64a2e8f7c6ac2132da44c6d5
doc_id: 919869
cord_uid: h45zlv8f

The title compound, C(23)H(25)BrN(2)O(3), crystallizes with two independent mol­ecules in the asymmetric unit (Z′ = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexa­hydro­quinoline ring [dihedral angles of 78.55 (9) and 89.70 (8)° in molecules A and B, respectively]. The indole ring is planar in both molecules [maximum deviations = 0.021 (3) and −0.020 (3) Å for the N atom] while the cyclo­hexene ring has adopts a sofa conformation. In the crystal, mol­ecules are linked by pairs of N—H⋯O hydrogen bonds, forming dimers with R (1) (2)(6) ring motifs. These dimers are connected by N—H⋯O hydrogen bonds, generating chains along [110]. A C—H⋯O contact occurs between the independent mol­ecules.

The title compound, C 23 H 25 BrN 2 O 3 , crystallizes with two independent molecules in the asymmetric unit (Z 0 = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexahydroquinoline ring [dihedral angles of 78.55 (9) and 89.70 (8) in molecules A and B, respectively]. The indole ring is planar in both molecules [maximum deviations = 0.021 (3) and À0.020 (3) Å for the N atom] while the cyclohexene ring has adopts a sofa conformation. In the crystal, molecules are linked by pairs of N-HÁ Á ÁO hydrogen bonds, forming dimers with R 1 2 (6) ring motifs. These dimers are connected by N-HÁ Á ÁO hydrogen bonds, generating chains along [110] . A C-HÁ Á ÁO contact occurs between the independent molecules.

For biological properties of 1,4-dihydropyridines, see : Triggle, (2003); Ş afak & Ş imşek (2006) . For the introduction of nifedipine into clinical use, see: Gordeev et al. (1998) . For a description of the Cambridge Structural Database, see: Allen, (2002) . For geometric analysis, see: Cremer & Pople (1975) . Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) Àx; y þ 1 2 ; Àz þ 1 2 ; (ii) x þ 1; y; z; (iii) Àx; y À 1 2 ; Àz þ 1 2 .

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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.

Since the introduction of nifedipine into clinical use, many modifications have been made such as fusing one of the carbonyl groups into the ring system or substitution of the phenyl ring with heteroaromatic rings in order to elucidate the SARs (severe acute respiratory syndrome) and to enhance calcium-modulating effects (Gordeev et al., 1998) . Following on from these results, we synthesized the title compound and determined its structure.

In the title compound (I), (Fig. 1, Fig. 2 ), the 5-bromo-1H-indole ring is almost planar in both of the molecules with a maximum deviation from the mean plane of 0.021 (3) Å for atom N2A and -0.020 (3) Å for atom N2B. The cyclohexene rings adopt a sofa conformation and are puckered with puckering parameters in molecule A and B (Cremer & Pople, 1975 ) of Q T = 0.472 (4) Å, θ = 120.7 (5) °, φ = 295.1 (5) ° and Q T = 0.475 (4) Å, θ = 62.7 (4) °, φ = 120.5 (4) °, respectively. The values of the bond lengths (Allen, 2002) and angles in (I) are in normal ranges and are comparable with those of related structures (El-Khouly et al., 2012; Öztürk Yildirim et al., 2012) .

In the crystal, molecules are linked by pairs of intermolecular N-H···O hydrogen bonds, forming dimers with R 1 2 (6) ring motifs (Bernstein et al., 1995; Etter et al., 1990) , and these dimers are connected by N-H···O hydrogen bonds, generating one-dimensional chains along [110] (Table 1, Fig. 3 ).

The title compound was prepared by refluxing 4,4-dimethyl-1,3-cyclohexanedione (0.001 mol), ethyl acetoacetate (0.001 mol), 6-bromoindole-2-carbaldehyde (0.001 mol) and ammonium acetate (0.005 mol) in methanol for 8 h. Crystals were grown by slow evaporation of a methanol solution. 

All H atoms were placed in idealized positions (C-H = 0.95-0.99 Å and N-H = 0.88 Å) and refined as riding atoms with U iso (H) = 1.2U eq (C or N) or 1.5 U eq (C methyl ). A rotating-group model was applied for the methyl groups. The highest residual electron density peak and the deepest hole are located at 0.86 and 0.82 Å from Br1B, respectively. Forty three outliers,(1 0 0), (-3 6 2), (2 4 0(, (-1 2 7), (1 3 6), (-4 6 2), (1 4 1), (3 1 3), (4 5 1), (-1 0 4), (-11 5 5), (-2 0 12), (-8 6 10), (-3 1 8), (-4 2 4), (3 1 2), (0 5 3), (6 2 1), (-2 1 8), (4 8 9), (-3 3 9), (-7 0 12), (-3 2 8), (-9 3 5), (-8 7 6), (-1 1 1), (-1 1 10), (-4 4 1), (-4 2 5), (-9 9 20), (-3 9 1), (-6 2 3), (-2 0 6), (-9 4 5), (-1 7 3), (3 1 5), (2 4 3), (2 4 4), (-11 3 5), (0 0 6), (0 1 10), (-5 3 2) and (1 8 3), were omitted in the final refinement. 

Agilent Xcalibur (Ruby, Gemini) diffractometer Radiation source: Enhance (Cu) X-ray Source Graphite monochromator Detector resolution: 10.5081 pixels mm -1 ω scans Absorption correction: analytical [(Clark & Reid, 1995) implemented in CrysAlis RED (Agilent (2011)]

T min = 0.270, T max = 0.514 17300 measured reflections 8621 independent reflections 7227 reflections with I > 2σ(I) 

Special details Experimental. The crystals were very fragile. On cutting the crystals shattered so the smallest viable crystal was selected and an incident collimator of 1.0 mm was used. Analytical numeric absorption correction using a multifaceted crystal model (Clark & Reid, 1995) . 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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

x (14) 

C18B-O3B-C19B

C1A-N1A-H1AA 118.7 C1B-N1B-H1BA 118.9 C9A-N1A-H1AA 118.7 C9B-N1B-H1BA 118

C17A-N2A-H2AC 125.5 C16B-N2B-H2BC 125.8 C16A-N2A-H2AC 125.5 C17B-N2B-H2BC 125.8 C6A-C1A-N1A

) C6B-C1B-C2B 124.1 (3) N1A-C1A-C2A

C9A-N1A-C1A-C6A 9.0 (5) C9B-N1B-C1B-C6B −12

) C6B-C1B-C2B-C3B −19

) N1B-C1B-C2B-C3B 161

) C1B-C2B-C3B-C4B 50

) C2B-C3B-C4B-C23B −

) C2B-C3B-C4B-C22B

) C2B-C3B-C4B-C5B −

C3A-C4A-C5A-O1A 160.1 (4) C23B-C4B-C5B-O1B −

) C22B-C4B-C5B-O1B

) C3B-C4B-C5B-O1B −

) C23B-C4B-C5B-C6B 140

C22A-C4A-C5A-C6A 100.4 (4) C22B-C4B-C5B-C6B −99

) C3B-C4B-C5B-C6B

) N1B-C1B-C6B-C5B

C2A-C1A-C6A-C5A 4.7 (5) C2B-C1B-C6B-C5B −10

) C2B-C1B-C6B-C7B

) O1B-C5B-C6B-C1B −

C4A-C5A-C6A-C1A −7.8 (5) C4B-C5B-C6B-C1B

E68, o3404-o3405 C4A-C5A-C6A-C7A 168.2 (3) C4B-C5B-C6B-C7B −173

C1A-C6A-C7A-C10A 103.4 (3) C1B-C6B-C7B-C10B −

C5A-C6A-C7A-C10A −72.6 (4) C5B-C6B-C7B-C10B

C1A-C6A-C7A-C8A −21.5 (4) C1B-C6B-C7B-C8B

) C10B-C7B-C8B-C9B

C6A-C7A-C8A-C9A 19.7 (4) C6B-C7B-C8B-C9B −

) C10B-C7B-C8B-C18B −

) C6B-C7B-C8B-C18B

) C18B-C8B-C9B-N1B −

) C7B-C8B-C9B-C21B −

) C1B-N1B-C9B-C8B

) C1B-N1B-C9B-C21B −163

) C6B-C7B-C10B-C17B −

) C6B-C7B-C10B-C11B

) C8B-C7B-C10B-C11B −71

C17A-C10A-C11A-C12A 178.0 (3) C17B-C10B-C11B-C12B −

) C7B-C10B-C11B-C16B −179

) C10B-C11B-C12B-C13B 179

) C11B-C12B-C13B-Br1B

) Br1B-C13B-C14B-C15B 179

) C17B-N2B-C16B-C15B −178

C14A-C15A-C16A-C11A 0.2 (5) C14B-C15B-C16B-C11B 2.0 (4) C12A-C11A-C16A-N2A −177

C10A-C11A-C16A-N2A 1.5 (3) C10B-C11B-C16B-N2B −0

) C10B-C11B-C16B-C15B

) C11B-C10B-C17B-N2B −0

C11A-C10A-C17A-N2A 0.1 (3) C7B-C10B-C17B-N2B 179

) C19B-O3B-C18B-C8B −178

) C9B-C8B-C18B-O2B

C7A-C8A-C18A-O2A 10.4 (4) C7B-C8B-C18B-O2B −9

C9A-C8A-C18A-O3A 10.0 (4) C9B-C8B-C18B-O3B −9

) C7B-C8B-C18B-O3B 170

) C18B-O3B-C19B-C20B −176