organic compounds
rac-(Z)-Methyl 1-benzyl-3-[(3-hydroxyquinuclidin-2-ylidene)methyl]-1H-indole-6-carboxylate
aDept. of Pharm. Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA, and bDept. of Chemistry, University of Kentucky, Lexington KY 40506, USA
*Correspondence e-mail: pacrooks@uams.edu
In the title compound, C25H26N2O3, the double bond connecting the aza-bicyclic and indole units has Z geometry. The compound was obtained as a racemate, and since the crystal is centrosymmetric it contains equal amounts of the S and R enantiomers. However, the structure is disordered such that the contains both enantiomers in unequal amounts [refined occupancies 0.904 (2) and 0.096 (2)]. The dihedral angle between the benzene ring of the benzyl group and the mean plane of the indole ring is 76.07 (3) °. In the crystal, molecules are linked by O—H⋯Ocarbonyl hydrogen bonds into chains propagating in [110].
Related literature
For background literature, see: Sekhar et al., (2003), Amudhan et al., (2010). For the biological activity of N-benzyl indole quinuclidinone, see: Sonar et al. (2007). For a similar see: Sonar et al., (2004).
Experimental
Crystal data
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Data collection
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Refinement
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Data collection: COLLECT (Nonius, 1998); cell SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 and local procedures.
Supporting information
10.1107/S1600536812040731/hg5242sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536812040731/hg5242Isup2.hkl
The compound Z-methyl 1-benzyl-3-[(3-oxoquinuclidin-2-ylidene)methyl] -1H-indole-6-carboxylate was prepared by the available literature procedure (Sonar et al., 2004). To a stirred solution of Z-methyl 1-benzyl-3-((3-oxoquinuclidin-2-ylidene)methyl)-1H-indole-6-carboxylate (0.40 g, 1 mmol) in methanol (15 ml) at 273 K was added NaBH4 (0.38 g, 10 mmol) over a period of 15 min and stirring was continued for 2 h at room temperature. Water (50 ml) was added and the mixture was extracted with CHCl3 (3 times 10 ml). The combined organic layers were dried over Na2SO4 and evaporated to give the title compound as a white solid. Recrystallization from methanol afforded colorless needles suitable for X-ray analysis.
H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained distances of 0.98 Å (RCH3), 0.99 Å (R2CH2), 1.00 Å (R3CH), 0.95 Å (Csp2H), 0.84 Å (O—H), and with Uiso(H) values set to either 1.2Ueq or 1.5Ueq (RCH3, OH) of the attached atom.
To ensure satisfactory
of the disordered parts of the structure, restraints were needed. The restraints (SHELXL97 commands SAME, DELU, SAME) were used to ensure similar geometries and displacement parameters of closely proximate, chemically similar groups.Data collection: COLLECT (Nonius, 1998); cell
SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and local procedures.Fig. 1. A view of the molecule with displacement ellipsoids drawn at the 50% probability level. |
C25H26N2O3 | Z = 2 |
Mr = 402.48 | F(000) = 428 |
Triclinic, P1 | Dx = 1.329 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 6.1619 (1) Å | Cell parameters from 4571 reflections |
b = 10.3119 (2) Å | θ = 1.0–27.5° |
c = 16.5959 (3) Å | µ = 0.09 mm−1 |
α = 75.6705 (7)° | T = 90 K |
β = 80.0939 (7)° | Block, yellow |
γ = 85.9410 (7)° | 0.28 × 0.22 × 0.12 mm |
V = 1006.04 (3) Å3 |
Nonius KappaCCD diffractometer | 3831 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.024 |
Graphite monochromator | θmax = 27.5°, θmin = 2.0° |
Detector resolution: 9.1 pixels mm-1 | h = −8→8 |
ω scans at fixed χ = 55° | k = −13→13 |
9126 measured reflections | l = −21→21 |
4597 independent reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.039 | H-atom parameters constrained |
wR(F2) = 0.102 | w = 1/[σ2(Fo2) + (0.0442P)2 + 0.3522P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max = 0.001 |
4597 reflections | Δρmax = 0.27 e Å−3 |
312 parameters | Δρmin = −0.20 e Å−3 |
64 restraints | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.023 (4) |
C25H26N2O3 | γ = 85.9410 (7)° |
Mr = 402.48 | V = 1006.04 (3) Å3 |
Triclinic, P1 | Z = 2 |
a = 6.1619 (1) Å | Mo Kα radiation |
b = 10.3119 (2) Å | µ = 0.09 mm−1 |
c = 16.5959 (3) Å | T = 90 K |
α = 75.6705 (7)° | 0.28 × 0.22 × 0.12 mm |
β = 80.0939 (7)° |
Nonius KappaCCD diffractometer | 3831 reflections with I > 2σ(I) |
9126 measured reflections | Rint = 0.024 |
4597 independent reflections |
R[F2 > 2σ(F2)] = 0.039 | 64 restraints |
wR(F2) = 0.102 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.27 e Å−3 |
4597 reflections | Δρmin = −0.20 e Å−3 |
312 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-value wR and goodness of fit S are based on F2. Conventional R-values R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-values based on F2 are statistically about twice as large as those based on F, and R-values based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
N1 | 0.31767 (16) | 0.66937 (10) | 0.24130 (6) | 0.0190 (2) | |
O2 | 1.05912 (15) | 0.90627 (9) | 0.09629 (6) | 0.0280 (2) | |
O3 | 1.17472 (13) | 0.78520 (8) | 0.00096 (5) | 0.0213 (2) | |
C1 | 0.1919 (2) | 0.56139 (12) | 0.24673 (7) | 0.0196 (2) | |
H1 | 0.0613 | 0.5379 | 0.2861 | 0.024* | |
C2 | 0.28163 (19) | 0.49219 (11) | 0.18719 (7) | 0.0181 (2) | |
C3 | 0.47803 (19) | 0.56153 (11) | 0.14234 (7) | 0.0172 (2) | |
C4 | 0.64453 (19) | 0.53937 (11) | 0.07749 (7) | 0.0180 (2) | |
H4 | 0.6356 | 0.4677 | 0.0517 | 0.022* | |
C5 | 0.82107 (19) | 0.62300 (11) | 0.05167 (7) | 0.0182 (2) | |
H5 | 0.9329 | 0.6092 | 0.0072 | 0.022* | |
C6 | 0.83869 (19) | 0.72871 (11) | 0.08999 (7) | 0.0171 (2) | |
C7 | 0.67658 (19) | 0.75346 (11) | 0.15415 (7) | 0.0181 (2) | |
H7 | 0.6879 | 0.8245 | 0.1802 | 0.022* | |
C8 | 0.49701 (19) | 0.67018 (11) | 0.17875 (7) | 0.0171 (2) | |
C9 | 1.03202 (19) | 0.81587 (11) | 0.06408 (7) | 0.0184 (2) | |
C10 | 1.3663 (2) | 0.86728 (12) | −0.02905 (8) | 0.0230 (3) | |
H10A | 1.3191 | 0.9616 | −0.0455 | 0.035* | |
H10B | 1.4539 | 0.8408 | −0.0779 | 0.035* | |
H10C | 1.4557 | 0.8552 | 0.0159 | 0.035* | |
C11 | 0.2901 (2) | 0.75327 (12) | 0.30102 (8) | 0.0212 (3) | |
H11A | 0.1373 | 0.7463 | 0.3319 | 0.025* | |
H11B | 0.3117 | 0.8477 | 0.2696 | 0.025* | |
C12 | 0.4496 (2) | 0.71600 (12) | 0.36448 (7) | 0.0196 (3) | |
C13 | 0.4619 (2) | 0.79843 (13) | 0.41841 (8) | 0.0248 (3) | |
H13 | 0.3700 | 0.8769 | 0.4156 | 0.030* | |
C14 | 0.6069 (2) | 0.76729 (14) | 0.47622 (8) | 0.0302 (3) | |
H14 | 0.6149 | 0.8250 | 0.5122 | 0.036* | |
C15 | 0.7402 (2) | 0.65246 (15) | 0.48175 (8) | 0.0307 (3) | |
H15 | 0.8390 | 0.6309 | 0.5215 | 0.037* | |
C16 | 0.7282 (2) | 0.56959 (14) | 0.42883 (8) | 0.0300 (3) | |
H16 | 0.8186 | 0.4905 | 0.4325 | 0.036* | |
C17 | 0.5845 (2) | 0.60137 (13) | 0.37025 (8) | 0.0250 (3) | |
H17 | 0.5786 | 0.5441 | 0.3338 | 0.030* | |
C18 | 0.2112 (2) | 0.36924 (12) | 0.17230 (7) | 0.0203 (3) | |
H18 | 0.2905 | 0.3426 | 0.1244 | 0.024* | |
C19 | 0.0490 (3) | 0.28894 (14) | 0.21750 (9) | 0.0190 (3) | 0.904 (2) |
C20 | 0.0007 (2) | 0.15731 (14) | 0.19936 (9) | 0.0204 (3) | 0.904 (2) |
H20 | −0.0961 | 0.1753 | 0.1550 | 0.025* | 0.904 (2) |
O1 | 0.20291 (17) | 0.09447 (10) | 0.16992 (7) | 0.0268 (3) | 0.904 (2) |
H1A | 0.1766 | 0.0378 | 0.1445 | 0.040* | 0.904 (2) |
C21 | −0.1226 (3) | 0.07182 (18) | 0.28158 (11) | 0.0203 (4) | 0.904 (2) |
H21 | −0.1372 | −0.0216 | 0.2763 | 0.024* | 0.904 (2) |
C22 | 0.0068 (3) | 0.07145 (14) | 0.35275 (9) | 0.0237 (3) | 0.904 (2) |
H22A | 0.1614 | 0.0414 | 0.3378 | 0.028* | 0.904 (2) |
H22B | −0.0598 | 0.0092 | 0.4054 | 0.028* | 0.904 (2) |
C23 | −0.0005 (3) | 0.2159 (2) | 0.36551 (10) | 0.0232 (3) | 0.904 (2) |
H23A | −0.0995 | 0.2201 | 0.4186 | 0.028* | 0.904 (2) |
H23B | 0.1488 | 0.2397 | 0.3703 | 0.028* | 0.904 (2) |
N2 | −0.0804 (3) | 0.31334 (13) | 0.29406 (9) | 0.0209 (3) | 0.904 (2) |
C24 | −0.3148 (3) | 0.28641 (16) | 0.29584 (10) | 0.0258 (4) | 0.904 (2) |
H24A | −0.3657 | 0.3432 | 0.2447 | 0.031* | 0.904 (2) |
H24B | −0.4054 | 0.3110 | 0.3455 | 0.031* | 0.904 (2) |
C25 | −0.3496 (2) | 0.13790 (14) | 0.29981 (9) | 0.0243 (3) | 0.904 (2) |
H25A | −0.4259 | 0.0929 | 0.3563 | 0.029* | 0.904 (2) |
H25B | −0.4408 | 0.1311 | 0.2575 | 0.029* | 0.904 (2) |
C19' | 0.116 (2) | 0.2718 (12) | 0.2322 (7) | 0.013 (3)* | 0.096 (2) |
C20' | 0.080 (3) | 0.1336 (14) | 0.2189 (9) | 0.033 (4)* | 0.096 (2) |
H20' | 0.1935 | 0.0690 | 0.2434 | 0.039* | 0.096 (2) |
O1' | 0.1065 (19) | 0.1428 (11) | 0.1316 (6) | 0.035 (3)* | 0.096 (2) |
H1' | 0.0220 | 0.0896 | 0.1222 | 0.052* | 0.096 (2) |
C21' | −0.148 (3) | 0.0902 (19) | 0.2671 (11) | 0.039 (5)* | 0.096 (2) |
H21' | −0.1966 | 0.0125 | 0.2494 | 0.047* | 0.096 (2) |
C22' | −0.124 (3) | 0.0512 (14) | 0.3604 (9) | 0.036 (4)* | 0.096 (2) |
H22C | −0.2711 | 0.0409 | 0.3964 | 0.044* | 0.096 (2) |
H22D | −0.0383 | −0.0339 | 0.3739 | 0.044* | 0.096 (2) |
C23' | −0.005 (3) | 0.1654 (15) | 0.3737 (10) | 0.022 (4)* | 0.096 (2) |
H23C | −0.0666 | 0.1803 | 0.4300 | 0.027* | 0.096 (2) |
H23D | 0.1519 | 0.1378 | 0.3743 | 0.027* | 0.096 (2) |
N2' | −0.016 (2) | 0.2938 (14) | 0.3109 (8) | 0.021 (3)* | 0.096 (2) |
C24' | −0.240 (3) | 0.3146 (15) | 0.2931 (10) | 0.022 (4)* | 0.096 (2) |
H24C | −0.2543 | 0.4049 | 0.2558 | 0.026* | 0.096 (2) |
H24D | −0.3418 | 0.3118 | 0.3465 | 0.026* | 0.096 (2) |
C25' | −0.310 (2) | 0.2096 (15) | 0.2506 (10) | 0.036 (4)* | 0.096 (2) |
H25C | −0.4629 | 0.1816 | 0.2752 | 0.043* | 0.096 (2) |
H25D | −0.3038 | 0.2475 | 0.1893 | 0.043* | 0.096 (2) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0196 (5) | 0.0182 (5) | 0.0198 (5) | −0.0002 (4) | −0.0017 (4) | −0.0068 (4) |
O2 | 0.0274 (5) | 0.0277 (5) | 0.0337 (5) | −0.0079 (4) | −0.0019 (4) | −0.0166 (4) |
O3 | 0.0178 (4) | 0.0223 (4) | 0.0242 (4) | −0.0048 (3) | −0.0004 (3) | −0.0073 (3) |
C1 | 0.0183 (6) | 0.0188 (6) | 0.0211 (6) | −0.0006 (4) | −0.0034 (5) | −0.0034 (5) |
C2 | 0.0179 (6) | 0.0178 (5) | 0.0182 (5) | −0.0005 (4) | −0.0045 (4) | −0.0027 (4) |
C3 | 0.0180 (6) | 0.0162 (5) | 0.0174 (5) | 0.0000 (4) | −0.0057 (4) | −0.0023 (4) |
C4 | 0.0208 (6) | 0.0173 (5) | 0.0177 (5) | −0.0005 (4) | −0.0047 (4) | −0.0061 (4) |
C5 | 0.0176 (6) | 0.0194 (6) | 0.0182 (5) | 0.0007 (4) | −0.0028 (4) | −0.0058 (4) |
C6 | 0.0177 (6) | 0.0165 (5) | 0.0178 (5) | −0.0008 (4) | −0.0060 (4) | −0.0033 (4) |
C7 | 0.0209 (6) | 0.0156 (5) | 0.0192 (6) | 0.0006 (4) | −0.0063 (5) | −0.0055 (4) |
C8 | 0.0181 (6) | 0.0169 (5) | 0.0163 (5) | 0.0018 (4) | −0.0039 (4) | −0.0038 (4) |
C9 | 0.0186 (6) | 0.0181 (6) | 0.0194 (6) | 0.0008 (4) | −0.0061 (5) | −0.0048 (4) |
C10 | 0.0173 (6) | 0.0235 (6) | 0.0273 (6) | −0.0051 (5) | −0.0028 (5) | −0.0037 (5) |
C11 | 0.0233 (6) | 0.0190 (6) | 0.0223 (6) | 0.0025 (5) | −0.0014 (5) | −0.0088 (5) |
C12 | 0.0206 (6) | 0.0184 (6) | 0.0179 (5) | −0.0025 (4) | 0.0014 (4) | −0.0034 (4) |
C13 | 0.0289 (7) | 0.0210 (6) | 0.0245 (6) | −0.0008 (5) | −0.0021 (5) | −0.0070 (5) |
C14 | 0.0375 (8) | 0.0316 (7) | 0.0244 (7) | −0.0059 (6) | −0.0052 (6) | −0.0106 (5) |
C15 | 0.0287 (7) | 0.0395 (8) | 0.0236 (6) | −0.0015 (6) | −0.0069 (5) | −0.0052 (6) |
C16 | 0.0288 (7) | 0.0320 (7) | 0.0263 (7) | 0.0078 (6) | −0.0034 (5) | −0.0049 (6) |
C17 | 0.0300 (7) | 0.0230 (6) | 0.0218 (6) | 0.0029 (5) | −0.0030 (5) | −0.0069 (5) |
C18 | 0.0220 (6) | 0.0209 (6) | 0.0191 (6) | −0.0019 (5) | −0.0033 (5) | −0.0062 (5) |
C19 | 0.0175 (7) | 0.0211 (7) | 0.0195 (7) | 0.0005 (6) | −0.0064 (6) | −0.0048 (5) |
C20 | 0.0179 (7) | 0.0246 (7) | 0.0207 (7) | −0.0037 (5) | −0.0028 (6) | −0.0082 (5) |
O1 | 0.0232 (5) | 0.0290 (6) | 0.0325 (6) | −0.0072 (4) | 0.0033 (4) | −0.0194 (5) |
C21 | 0.0188 (7) | 0.0180 (7) | 0.0250 (8) | −0.0030 (5) | −0.0025 (6) | −0.0066 (6) |
C22 | 0.0238 (8) | 0.0230 (7) | 0.0233 (7) | 0.0025 (6) | −0.0058 (6) | −0.0035 (5) |
C23 | 0.0242 (8) | 0.0260 (9) | 0.0215 (8) | −0.0027 (7) | −0.0035 (5) | −0.0095 (7) |
N2 | 0.0193 (8) | 0.0196 (6) | 0.0230 (7) | −0.0018 (5) | −0.0001 (6) | −0.0055 (5) |
C24 | 0.0156 (8) | 0.0233 (8) | 0.0344 (9) | 0.0021 (6) | −0.0008 (6) | −0.0025 (6) |
C25 | 0.0174 (7) | 0.0251 (7) | 0.0302 (8) | −0.0037 (5) | −0.0030 (5) | −0.0059 (6) |
N1—C1 | 1.3772 (15) | C19—C20 | 1.5204 (18) |
N1—C8 | 1.3787 (15) | C20—O1 | 1.4296 (18) |
N1—C11 | 1.4510 (15) | C20—C21 | 1.536 (2) |
O2—C9 | 1.2174 (14) | C20—H20 | 1.0000 |
O3—C9 | 1.3334 (14) | O1—H1A | 0.8400 |
O3—C10 | 1.4450 (14) | C21—C25 | 1.528 (2) |
C1—C2 | 1.3771 (17) | C21—C22 | 1.533 (2) |
C1—H1 | 0.9500 | C21—H21 | 1.0000 |
C2—C3 | 1.4419 (16) | C22—C23 | 1.552 (2) |
C2—C18 | 1.4583 (16) | C22—H22A | 0.9900 |
C3—C4 | 1.4042 (16) | C22—H22B | 0.9900 |
C3—C8 | 1.4185 (15) | C23—N2 | 1.483 (2) |
C4—C5 | 1.3784 (16) | C23—H23A | 0.9900 |
C4—H4 | 0.9500 | C23—H23B | 0.9900 |
C5—C6 | 1.4100 (15) | N2—C24 | 1.484 (2) |
C5—H5 | 0.9500 | C24—C25 | 1.545 (2) |
C6—C7 | 1.3890 (16) | C24—H24A | 0.9900 |
C6—C9 | 1.4819 (16) | C24—H24B | 0.9900 |
C7—C8 | 1.3907 (16) | C25—H25A | 0.9900 |
C7—H7 | 0.9500 | C25—H25B | 0.9900 |
C10—H10A | 0.9800 | C19'—N2' | 1.473 (13) |
C10—H10B | 0.9800 | C19'—C20' | 1.532 (14) |
C10—H10C | 0.9800 | C20'—O1' | 1.410 (14) |
C11—C12 | 1.5245 (17) | C20'—C21' | 1.525 (16) |
C11—H11A | 0.9900 | C20'—H20' | 1.0000 |
C11—H11B | 0.9900 | O1'—H1' | 0.8400 |
C12—C17 | 1.3894 (17) | C21'—C22' | 1.530 (16) |
C12—C13 | 1.3924 (17) | C21'—C25' | 1.534 (16) |
C13—C14 | 1.3871 (19) | C21'—H21' | 1.0000 |
C13—H13 | 0.9500 | C22'—C23' | 1.511 (15) |
C14—C15 | 1.386 (2) | C22'—H22C | 0.9900 |
C14—H14 | 0.9500 | C22'—H22D | 0.9900 |
C15—C16 | 1.382 (2) | C23'—N2' | 1.474 (14) |
C15—H15 | 0.9500 | C23'—H23C | 0.9900 |
C16—C17 | 1.3906 (18) | C23'—H23D | 0.9900 |
C16—H16 | 0.9500 | N2'—C24' | 1.449 (14) |
C17—H17 | 0.9500 | C24'—C25' | 1.552 (15) |
C18—C19' | 1.317 (11) | C24'—H24C | 0.9900 |
C18—C19 | 1.3414 (18) | C24'—H24D | 0.9900 |
C18—H18 | 0.9500 | C25'—H25C | 0.9900 |
C19—N2 | 1.4473 (17) | C25'—H25D | 0.9900 |
C1—N1—C8 | 108.58 (10) | C25—C21—C20 | 107.91 (15) |
C1—N1—C11 | 125.67 (10) | C22—C21—C20 | 108.15 (13) |
C8—N1—C11 | 124.84 (10) | C25—C21—H21 | 110.5 |
C9—O3—C10 | 116.16 (9) | C22—C21—H21 | 110.5 |
C2—C1—N1 | 110.67 (11) | C20—C21—H21 | 110.5 |
C2—C1—H1 | 124.7 | C21—C22—C23 | 108.31 (12) |
N1—C1—H1 | 124.7 | C21—C22—H22A | 110.0 |
C1—C2—C3 | 105.81 (10) | C23—C22—H22A | 110.0 |
C1—C2—C18 | 129.80 (11) | C21—C22—H22B | 110.0 |
C3—C2—C18 | 124.28 (11) | C23—C22—H22B | 110.0 |
C4—C3—C8 | 118.63 (10) | H22A—C22—H22B | 108.4 |
C4—C3—C2 | 134.05 (11) | N2—C23—C22 | 110.86 (12) |
C8—C3—C2 | 107.24 (10) | N2—C23—H23A | 109.5 |
C5—C4—C3 | 119.14 (10) | C22—C23—H23A | 109.5 |
C5—C4—H4 | 120.4 | N2—C23—H23B | 109.5 |
C3—C4—H4 | 120.4 | C22—C23—H23B | 109.5 |
C4—C5—C6 | 121.22 (11) | H23A—C23—H23B | 108.1 |
C4—C5—H5 | 119.4 | C19—N2—C23 | 107.06 (13) |
C6—C5—H5 | 119.4 | C19—N2—C24 | 109.12 (13) |
C7—C6—C5 | 121.04 (10) | C23—N2—C24 | 108.13 (12) |
C7—C6—C9 | 117.76 (10) | N2—C24—C25 | 112.14 (12) |
C5—C6—C9 | 121.20 (10) | N2—C24—H24A | 109.2 |
C6—C7—C8 | 117.38 (10) | C25—C24—H24A | 109.2 |
C6—C7—H7 | 121.3 | N2—C24—H24B | 109.2 |
C8—C7—H7 | 121.3 | C25—C24—H24B | 109.2 |
N1—C8—C7 | 129.70 (10) | H24A—C24—H24B | 107.9 |
N1—C8—C3 | 107.67 (10) | C21—C25—C24 | 107.59 (12) |
C7—C8—C3 | 122.56 (11) | C21—C25—H25A | 110.2 |
O2—C9—O3 | 123.10 (11) | C24—C25—H25A | 110.2 |
O2—C9—C6 | 124.16 (11) | C21—C25—H25B | 110.2 |
O3—C9—C6 | 112.74 (9) | C24—C25—H25B | 110.2 |
O3—C10—H10A | 109.5 | H25A—C25—H25B | 108.5 |
O3—C10—H10B | 109.5 | C18—C19'—N2' | 123.0 (10) |
H10A—C10—H10B | 109.5 | C18—C19'—C20' | 123.3 (9) |
O3—C10—H10C | 109.5 | N2'—C19'—C20' | 112.0 (9) |
H10A—C10—H10C | 109.5 | O1'—C20'—C21' | 114.7 (13) |
H10B—C10—H10C | 109.5 | O1'—C20'—C19' | 108.5 (11) |
N1—C11—C12 | 113.36 (10) | C21'—C20'—C19' | 107.0 (12) |
N1—C11—H11A | 108.9 | O1'—C20'—H20' | 108.8 |
C12—C11—H11A | 108.9 | C21'—C20'—H20' | 108.8 |
N1—C11—H11B | 108.9 | C19'—C20'—H20' | 108.8 |
C12—C11—H11B | 108.9 | C20'—O1'—H1' | 109.5 |
H11A—C11—H11B | 107.7 | C20'—C21'—C22' | 106.2 (13) |
C17—C12—C13 | 118.55 (11) | C20'—C21'—C25' | 108.6 (14) |
C17—C12—C11 | 121.83 (11) | C22'—C21'—C25' | 109.8 (14) |
C13—C12—C11 | 119.62 (11) | C20'—C21'—H21' | 110.7 |
C14—C13—C12 | 120.72 (12) | C22'—C21'—H21' | 110.7 |
C14—C13—H13 | 119.6 | C25'—C21'—H21' | 110.7 |
C12—C13—H13 | 119.6 | C23'—C22'—C21' | 104.9 (12) |
C15—C14—C13 | 120.31 (12) | C23'—C22'—H22C | 110.8 |
C15—C14—H14 | 119.8 | C21'—C22'—H22C | 110.8 |
C13—C14—H14 | 119.8 | C23'—C22'—H22D | 110.8 |
C16—C15—C14 | 119.39 (12) | C21'—C22'—H22D | 110.8 |
C16—C15—H15 | 120.3 | H22C—C22'—H22D | 108.8 |
C14—C15—H15 | 120.3 | N2'—C23'—C22' | 116.0 (12) |
C15—C16—C17 | 120.38 (13) | N2'—C23'—H23C | 108.3 |
C15—C16—H16 | 119.8 | C22'—C23'—H23C | 108.3 |
C17—C16—H16 | 119.8 | N2'—C23'—H23D | 108.3 |
C12—C17—C16 | 120.65 (12) | C22'—C23'—H23D | 108.3 |
C12—C17—H17 | 119.7 | H23C—C23'—H23D | 107.4 |
C16—C17—H17 | 119.7 | C24'—N2'—C23' | 107.8 (12) |
C19'—C18—C2 | 123.8 (5) | C24'—N2'—C19' | 104.4 (11) |
C19—C18—C2 | 128.40 (12) | C23'—N2'—C19' | 105.6 (11) |
C19'—C18—H18 | 115.1 | N2'—C24'—C25' | 113.8 (11) |
C19—C18—H18 | 115.8 | N2'—C24'—H24C | 108.8 |
C2—C18—H18 | 115.8 | C25'—C24'—H24C | 108.8 |
C18—C19—N2 | 122.23 (12) | N2'—C24'—H24D | 108.8 |
C18—C19—C20 | 123.71 (12) | C25'—C24'—H24D | 108.8 |
N2—C19—C20 | 113.72 (11) | H24C—C24'—H24D | 107.7 |
O1—C20—C19 | 109.43 (11) | C21'—C25'—C24' | 106.2 (12) |
O1—C20—C21 | 112.52 (13) | C21'—C25'—H25C | 110.5 |
C19—C20—C21 | 106.93 (11) | C24'—C25'—H25C | 110.5 |
O1—C20—H20 | 109.3 | C21'—C25'—H25D | 110.5 |
C19—C20—H20 | 109.3 | C24'—C25'—H25D | 110.5 |
C21—C20—H20 | 109.3 | H25C—C25'—H25D | 108.7 |
C25—C21—C22 | 109.07 (13) | ||
C8—N1—C1—C2 | −1.61 (13) | C2—C18—C19—C20 | −175.48 (13) |
C11—N1—C1—C2 | −171.05 (10) | C18—C19—C20—O1 | 35.0 (2) |
N1—C1—C2—C3 | 0.62 (13) | N2—C19—C20—O1 | −138.42 (14) |
N1—C1—C2—C18 | 176.88 (11) | C18—C19—C20—C21 | 157.16 (17) |
C1—C2—C3—C4 | 177.33 (12) | N2—C19—C20—C21 | −16.29 (19) |
C18—C2—C3—C4 | 0.8 (2) | O1—C20—C21—C25 | −171.58 (11) |
C1—C2—C3—C8 | 0.56 (12) | C19—C20—C21—C25 | 68.25 (16) |
C18—C2—C3—C8 | −175.96 (10) | O1—C20—C21—C22 | 70.56 (15) |
C8—C3—C4—C5 | 0.38 (16) | C19—C20—C21—C22 | −49.60 (17) |
C2—C3—C4—C5 | −176.11 (12) | C25—C21—C22—C23 | −51.32 (16) |
C3—C4—C5—C6 | 0.94 (17) | C20—C21—C22—C23 | 65.79 (16) |
C4—C5—C6—C7 | −1.10 (17) | C21—C22—C23—N2 | −13.47 (17) |
C4—C5—C6—C9 | 178.01 (11) | C18—C19—N2—C23 | −104.06 (18) |
C5—C6—C7—C8 | −0.11 (16) | C20—C19—N2—C23 | 69.50 (18) |
C9—C6—C7—C8 | −179.26 (10) | C18—C19—N2—C24 | 139.14 (17) |
C1—N1—C8—C7 | −175.07 (12) | C20—C19—N2—C24 | −47.30 (18) |
C11—N1—C8—C7 | −5.52 (19) | C22—C23—N2—C19 | −50.65 (16) |
C1—N1—C8—C3 | 1.92 (12) | C22—C23—N2—C24 | 66.81 (15) |
C11—N1—C8—C3 | 171.47 (10) | C19—N2—C24—C25 | 64.01 (16) |
C6—C7—C8—N1 | 178.07 (11) | C23—N2—C24—C25 | −52.12 (16) |
C6—C7—C8—C3 | 1.47 (16) | C22—C21—C25—C24 | 65.38 (16) |
C4—C3—C8—N1 | −178.88 (10) | C20—C21—C25—C24 | −51.89 (16) |
C2—C3—C8—N1 | −1.52 (12) | N2—C24—C25—C21 | −12.01 (18) |
C4—C3—C8—C7 | −1.63 (17) | C19—C18—C19'—N2' | −82.4 (17) |
C2—C3—C8—C7 | 175.73 (10) | C2—C18—C19'—N2' | 27.3 (16) |
C10—O3—C9—O2 | −0.86 (16) | C19—C18—C19'—C20' | 81.5 (17) |
C10—O3—C9—C6 | 178.94 (9) | C2—C18—C19'—C20' | −168.7 (10) |
C7—C6—C9—O2 | 1.15 (17) | C18—C19'—C20'—O1' | −16.1 (19) |
C5—C6—C9—O2 | −177.99 (11) | N2'—C19'—C20'—O1' | 149.4 (13) |
C7—C6—C9—O3 | −178.65 (10) | C18—C19'—C20'—C21' | −140.4 (14) |
C5—C6—C9—O3 | 2.21 (15) | N2'—C19'—C20'—C21' | 25.1 (17) |
C1—N1—C11—C12 | 98.55 (13) | O1'—C20'—C21'—C22' | 165.5 (13) |
C8—N1—C11—C12 | −69.23 (14) | C19'—C20'—C21'—C22' | −74.1 (15) |
N1—C11—C12—C17 | −8.29 (16) | O1'—C20'—C21'—C25' | −76.4 (17) |
N1—C11—C12—C13 | 171.63 (11) | C19'—C20'—C21'—C25' | 44.0 (16) |
C17—C12—C13—C14 | 0.46 (19) | C20'—C21'—C22'—C23' | 48.1 (17) |
C11—C12—C13—C14 | −179.46 (12) | C25'—C21'—C22'—C23' | −69.2 (17) |
C12—C13—C14—C15 | −0.7 (2) | C21'—C22'—C23'—N2' | 21 (2) |
C13—C14—C15—C16 | 0.3 (2) | C22'—C23'—N2'—C24' | 42.2 (18) |
C14—C15—C16—C17 | 0.3 (2) | C22'—C23'—N2'—C19' | −68.9 (17) |
C13—C12—C17—C16 | 0.21 (19) | C18—C19'—N2'—C24' | 92.0 (15) |
C11—C12—C17—C16 | −179.87 (12) | C20'—C19'—N2'—C24' | −73.5 (15) |
C15—C16—C17—C12 | −0.6 (2) | C18—C19'—N2'—C23' | −154.4 (13) |
C1—C2—C18—C19' | −32.0 (8) | C20'—C19'—N2'—C23' | 40.0 (15) |
C3—C2—C18—C19' | 143.6 (8) | C23'—N2'—C24'—C25' | −64.7 (16) |
C1—C2—C18—C19 | −5.1 (2) | C19'—N2'—C24'—C25' | 47.2 (16) |
C3—C2—C18—C19 | 170.57 (14) | C20'—C21'—C25'—C24' | −67.2 (16) |
C19'—C18—C19—N2 | 83.7 (14) | C22'—C21'—C25'—C24' | 48.5 (17) |
C2—C18—C19—N2 | −2.6 (2) | N2'—C24'—C25'—C21' | 18.4 (18) |
C19'—C18—C19—C20 | −89.2 (14) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1A···O2i | 0.84 | 1.97 | 2.7989 (13) | 169 |
Symmetry code: (i) x−1, y−1, z. |
Experimental details
Crystal data | |
Chemical formula | C25H26N2O3 |
Mr | 402.48 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 90 |
a, b, c (Å) | 6.1619 (1), 10.3119 (2), 16.5959 (3) |
α, β, γ (°) | 75.6705 (7), 80.0939 (7), 85.9410 (7) |
V (Å3) | 1006.04 (3) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.28 × 0.22 × 0.12 |
Data collection | |
Diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9126, 4597, 3831 |
Rint | 0.024 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.102, 1.04 |
No. of reflections | 4597 |
No. of parameters | 312 |
No. of restraints | 64 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.27, −0.20 |
Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008) and local procedures.
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1A···O2i | 0.84 | 1.97 | 2.7989 (13) | 169.4 |
Symmetry code: (i) x−1, y−1, z. |
Acknowledgements
This investigation was supported by NIH/National Cancer Institute grant PO1 CA140409.
References
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The N-benzyl indole quinuclidin-3-one moiety has been found to possess interesting biological properties which range from NADPH oxidase activity (Sekhar et al., 2003), thermal sensitizing activity to radiation treatment (Sonar et al., 2007), and also exhibit antiangiogenic properties (Amudhan et al., 2010). Previously, we reported the crystal structure of Z-(S)-2-(1- phenylsulfonyl-1H-indol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol (Sonar et al., 2004) and in continuation of our research work on the N-benzyl indole quinuclidin-3-one scaffold (Sonar et al., 2007) we designed and synthesized a novel series of carboxymethyl N-benzyl indole quinuclidin-3-ones as potent anticancer agents. The title compound was prepared by the reduction of Z-methyl 1-benzyl-3-[(3-oxoquinuclidin-2-ylidene)methyl]-1H-indole-6-carboxylate with NaBH4 in methanol at room temperature (Sonar et al., 2004). Recrystallization of the title compound from methanol afforded colorless needles that were suitable for X-ray analysis.
The X-ray studies revealed that the title compound is the Z isomer having the C2—C18 bond in a trans position with respect to the C19—C20 bond. The double bond (C18═C19) has a nearly planar atomic arrangement, since the r.m.s. deviation from the best plane passing through atoms N2, C19, C20, C18 and C2 is 0.265 (1) Å. In this molecule, the azabicyclic system presents very small distortions around atoms N2, C24, C21, C22, C23 and C20. The value of the C1—C2—C18—C19 torsion angle [-5.1 (2)°] indicates the deviation of the indole ring from the plane of the double bond connected to the azabicyclic ring. The dihedral angle between the benzene ring of the benzyl group and with the mean plane of the indole ring is 76.07 (3) Å. The crystal of the title compound is a racemic equimolar mixture of R and S configurations. However, the structure is disordered such that the asymmetric unit contains both enantiomers, but in unequal amounts [refined occupancies 0.904 (2) and 0.096 (2)]. The hydrogen atom of the disordered OH group is involved in an intermolecular hydrogen bond with the carbonyl oxygen O2 on an adjacent molecule, thus forming an infinite chain-like structure along the (110) direction.