organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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COMMUNICATIONS
ISSN: 2056-9890

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

(Received 13 August 2012; accepted 26 September 2012; online 13 October 2012)

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 asymmetric unit 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[Sekhar, K. R., Crooks, P. A., Sonar, V. N., Friedman, D. B., Chan, J. Y., Meredith, M. J., Stames, J. H., Kelton, K. R., Summar, S. R., Sasi, S. & Freeman, M. L. (2003). Cancer Res. 63, 5636-5645.]), Amudhan et al., (2010[Amudhan, V., Reddy, Y. T., Sonar, V. N., Venkatraj, M., Crooks, P. A., Michael, L., Freeman, M. L. & Sekhar, K. R. (2010). Bioorg. Med. Chem. Lett. 20, 7323-7326.]). For the biological activity of N-benzyl indole quinuclidinone, see: Sonar et al. (2007[Sonar, V. N., Reddy, Y. T., Sekhar, K. R., Sowmya, S., Freeman, M. L. & Crooks, P. A. (2007). Bioorg. Med. Chem. Lett. 17(24), 6821-6824.]). For a similar crystal structure, see: Sonar et al., (2004[Sonar, V. N., Parkin, S. & Crooks, P. A. (2004). Acta Cryst. C60, o659-o661.]).

[Scheme 1]

Experimental

Crystal data
  • C25H26N2O3

  • Mr = 402.48

  • Triclinic, [P \overline 1]

  • a = 6.1619 (1) Å

  • b = 10.3119 (2) Å

  • c = 16.5959 (3) Å

  • α = 75.6705 (7)°

  • β = 80.0939 (7)°

  • γ = 85.9410 (7)°

  • V = 1006.04 (3) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 90 K

  • 0.28 × 0.22 × 0.12 mm

Data collection
  • Nonius KappaCCD diffractometer

  • 9126 measured reflections

  • 4597 independent reflections

  • 3831 reflections with I > 2σ(I)

  • Rint = 0.024

Refinement
  • R[F2 > 2σ(F2)] = 0.039

  • wR(F2) = 0.102

  • S = 1.04

  • 4597 reflections

  • 312 parameters

  • 64 restraints

  • H-atom parameters constrained

  • Δρmax = 0.27 e Å−3

  • Δρmin = −0.20 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1A⋯O2i 0.84 1.97 2.7989 (13) 169
Symmetry code: (i) x-1, y-1, z.

Data collection: COLLECT (Nonius, 1998[Nonius (1998). COLLECT. Nonius, BV, Delft, The Netherlands.]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO-SMN (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307-326. New York: Academic Press.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: XP in SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97 and local procedures.

Supporting information


Comment top

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 (C18C19) 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.

Related literature top

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 crystal structure, see: Sonar et al., (2004).

Experimental top

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.

Refinement top

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 refinement 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.

Computing details top

Data collection: COLLECT (Nonius, 1998); cell refinement: 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.

Figures top
[Figure 1] Fig. 1. A view of the molecule with displacement ellipsoids drawn at the 50% probability level.
rac-(Z)-Methyl 1-benzyl-3-[(3-hydroxyquinuclidin-2-ylidene)methyl]-1H-indole-6- carboxylate top
Crystal data top
C25H26N2O3Z = 2
Mr = 402.48F(000) = 428
Triclinic, P1Dx = 1.329 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.1619 (1) ÅCell parameters from 4571 reflections
b = 10.3119 (2) Åθ = 1.0–27.5°
c = 16.5959 (3) ŵ = 0.09 mm1
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
Data collection top
Nonius KappaCCD
diffractometer
3831 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.024
Graphite monochromatorθmax = 27.5°, θmin = 2.0°
Detector resolution: 9.1 pixels mm-1h = 88
ω scans at fixed χ = 55°k = 1313
9126 measured reflectionsl = 2121
4597 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.039H-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 reflectionsΔρmax = 0.27 e Å3
312 parametersΔρmin = 0.20 e Å3
64 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.023 (4)
Crystal data top
C25H26N2O3γ = 85.9410 (7)°
Mr = 402.48V = 1006.04 (3) Å3
Triclinic, P1Z = 2
a = 6.1619 (1) ÅMo Kα radiation
b = 10.3119 (2) ŵ = 0.09 mm1
c = 16.5959 (3) ÅT = 90 K
α = 75.6705 (7)°0.28 × 0.22 × 0.12 mm
β = 80.0939 (7)°
Data collection top
Nonius KappaCCD
diffractometer
3831 reflections with I > 2σ(I)
9126 measured reflectionsRint = 0.024
4597 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.03964 restraints
wR(F2) = 0.102H-atom parameters constrained
S = 1.04Δρmax = 0.27 e Å3
4597 reflectionsΔρmin = 0.20 e Å3
312 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
N10.31767 (16)0.66937 (10)0.24130 (6)0.0190 (2)
O21.05912 (15)0.90627 (9)0.09629 (6)0.0280 (2)
O31.17472 (13)0.78520 (8)0.00096 (5)0.0213 (2)
C10.1919 (2)0.56139 (12)0.24673 (7)0.0196 (2)
H10.06130.53790.28610.024*
C20.28163 (19)0.49219 (11)0.18719 (7)0.0181 (2)
C30.47803 (19)0.56153 (11)0.14234 (7)0.0172 (2)
C40.64453 (19)0.53937 (11)0.07749 (7)0.0180 (2)
H40.63560.46770.05170.022*
C50.82107 (19)0.62300 (11)0.05167 (7)0.0182 (2)
H50.93290.60920.00720.022*
C60.83869 (19)0.72871 (11)0.08999 (7)0.0171 (2)
C70.67658 (19)0.75346 (11)0.15415 (7)0.0181 (2)
H70.68790.82450.18020.022*
C80.49701 (19)0.67018 (11)0.17875 (7)0.0171 (2)
C91.03202 (19)0.81587 (11)0.06408 (7)0.0184 (2)
C101.3663 (2)0.86728 (12)0.02905 (8)0.0230 (3)
H10A1.31910.96160.04550.035*
H10B1.45390.84080.07790.035*
H10C1.45570.85520.01590.035*
C110.2901 (2)0.75327 (12)0.30102 (8)0.0212 (3)
H11A0.13730.74630.33190.025*
H11B0.31170.84770.26960.025*
C120.4496 (2)0.71600 (12)0.36448 (7)0.0196 (3)
C130.4619 (2)0.79843 (13)0.41841 (8)0.0248 (3)
H130.37000.87690.41560.030*
C140.6069 (2)0.76729 (14)0.47622 (8)0.0302 (3)
H140.61490.82500.51220.036*
C150.7402 (2)0.65246 (15)0.48175 (8)0.0307 (3)
H150.83900.63090.52150.037*
C160.7282 (2)0.56959 (14)0.42883 (8)0.0300 (3)
H160.81860.49050.43250.036*
C170.5845 (2)0.60137 (13)0.37025 (8)0.0250 (3)
H170.57860.54410.33380.030*
C180.2112 (2)0.36924 (12)0.17230 (7)0.0203 (3)
H180.29050.34260.12440.024*
C190.0490 (3)0.28894 (14)0.21750 (9)0.0190 (3)0.904 (2)
C200.0007 (2)0.15731 (14)0.19936 (9)0.0204 (3)0.904 (2)
H200.09610.17530.15500.025*0.904 (2)
O10.20291 (17)0.09447 (10)0.16992 (7)0.0268 (3)0.904 (2)
H1A0.17660.03780.14450.040*0.904 (2)
C210.1226 (3)0.07182 (18)0.28158 (11)0.0203 (4)0.904 (2)
H210.13720.02160.27630.024*0.904 (2)
C220.0068 (3)0.07145 (14)0.35275 (9)0.0237 (3)0.904 (2)
H22A0.16140.04140.33780.028*0.904 (2)
H22B0.05980.00920.40540.028*0.904 (2)
C230.0005 (3)0.2159 (2)0.36551 (10)0.0232 (3)0.904 (2)
H23A0.09950.22010.41860.028*0.904 (2)
H23B0.14880.23970.37030.028*0.904 (2)
N20.0804 (3)0.31334 (13)0.29406 (9)0.0209 (3)0.904 (2)
C240.3148 (3)0.28641 (16)0.29584 (10)0.0258 (4)0.904 (2)
H24A0.36570.34320.24470.031*0.904 (2)
H24B0.40540.31100.34550.031*0.904 (2)
C250.3496 (2)0.13790 (14)0.29981 (9)0.0243 (3)0.904 (2)
H25A0.42590.09290.35630.029*0.904 (2)
H25B0.44080.13110.25750.029*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)
H20'0.19350.06900.24340.039*0.096 (2)
O1'0.1065 (19)0.1428 (11)0.1316 (6)0.035 (3)*0.096 (2)
H1'0.02200.08960.12220.052*0.096 (2)
C21'0.148 (3)0.0902 (19)0.2671 (11)0.039 (5)*0.096 (2)
H21'0.19660.01250.24940.047*0.096 (2)
C22'0.124 (3)0.0512 (14)0.3604 (9)0.036 (4)*0.096 (2)
H22C0.27110.04090.39640.044*0.096 (2)
H22D0.03830.03390.37390.044*0.096 (2)
C23'0.005 (3)0.1654 (15)0.3737 (10)0.022 (4)*0.096 (2)
H23C0.06660.18030.43000.027*0.096 (2)
H23D0.15190.13780.37430.027*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)
H24C0.25430.40490.25580.026*0.096 (2)
H24D0.34180.31180.34650.026*0.096 (2)
C25'0.310 (2)0.2096 (15)0.2506 (10)0.036 (4)*0.096 (2)
H25C0.46290.18160.27520.043*0.096 (2)
H25D0.30380.24750.18930.043*0.096 (2)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0196 (5)0.0182 (5)0.0198 (5)0.0002 (4)0.0017 (4)0.0068 (4)
O20.0274 (5)0.0277 (5)0.0337 (5)0.0079 (4)0.0019 (4)0.0166 (4)
O30.0178 (4)0.0223 (4)0.0242 (4)0.0048 (3)0.0004 (3)0.0073 (3)
C10.0183 (6)0.0188 (6)0.0211 (6)0.0006 (4)0.0034 (5)0.0034 (5)
C20.0179 (6)0.0178 (5)0.0182 (5)0.0005 (4)0.0045 (4)0.0027 (4)
C30.0180 (6)0.0162 (5)0.0174 (5)0.0000 (4)0.0057 (4)0.0023 (4)
C40.0208 (6)0.0173 (5)0.0177 (5)0.0005 (4)0.0047 (4)0.0061 (4)
C50.0176 (6)0.0194 (6)0.0182 (5)0.0007 (4)0.0028 (4)0.0058 (4)
C60.0177 (6)0.0165 (5)0.0178 (5)0.0008 (4)0.0060 (4)0.0033 (4)
C70.0209 (6)0.0156 (5)0.0192 (6)0.0006 (4)0.0063 (5)0.0055 (4)
C80.0181 (6)0.0169 (5)0.0163 (5)0.0018 (4)0.0039 (4)0.0038 (4)
C90.0186 (6)0.0181 (6)0.0194 (6)0.0008 (4)0.0061 (5)0.0048 (4)
C100.0173 (6)0.0235 (6)0.0273 (6)0.0051 (5)0.0028 (5)0.0037 (5)
C110.0233 (6)0.0190 (6)0.0223 (6)0.0025 (5)0.0014 (5)0.0088 (5)
C120.0206 (6)0.0184 (6)0.0179 (5)0.0025 (4)0.0014 (4)0.0034 (4)
C130.0289 (7)0.0210 (6)0.0245 (6)0.0008 (5)0.0021 (5)0.0070 (5)
C140.0375 (8)0.0316 (7)0.0244 (7)0.0059 (6)0.0052 (6)0.0106 (5)
C150.0287 (7)0.0395 (8)0.0236 (6)0.0015 (6)0.0069 (5)0.0052 (6)
C160.0288 (7)0.0320 (7)0.0263 (7)0.0078 (6)0.0034 (5)0.0049 (6)
C170.0300 (7)0.0230 (6)0.0218 (6)0.0029 (5)0.0030 (5)0.0069 (5)
C180.0220 (6)0.0209 (6)0.0191 (6)0.0019 (5)0.0033 (5)0.0062 (5)
C190.0175 (7)0.0211 (7)0.0195 (7)0.0005 (6)0.0064 (6)0.0048 (5)
C200.0179 (7)0.0246 (7)0.0207 (7)0.0037 (5)0.0028 (6)0.0082 (5)
O10.0232 (5)0.0290 (6)0.0325 (6)0.0072 (4)0.0033 (4)0.0194 (5)
C210.0188 (7)0.0180 (7)0.0250 (8)0.0030 (5)0.0025 (6)0.0066 (6)
C220.0238 (8)0.0230 (7)0.0233 (7)0.0025 (6)0.0058 (6)0.0035 (5)
C230.0242 (8)0.0260 (9)0.0215 (8)0.0027 (7)0.0035 (5)0.0095 (7)
N20.0193 (8)0.0196 (6)0.0230 (7)0.0018 (5)0.0001 (6)0.0055 (5)
C240.0156 (8)0.0233 (8)0.0344 (9)0.0021 (6)0.0008 (6)0.0025 (6)
C250.0174 (7)0.0251 (7)0.0302 (8)0.0037 (5)0.0030 (5)0.0059 (6)
Geometric parameters (Å, º) top
N1—C11.3772 (15)C19—C201.5204 (18)
N1—C81.3787 (15)C20—O11.4296 (18)
N1—C111.4510 (15)C20—C211.536 (2)
O2—C91.2174 (14)C20—H201.0000
O3—C91.3334 (14)O1—H1A0.8400
O3—C101.4450 (14)C21—C251.528 (2)
C1—C21.3771 (17)C21—C221.533 (2)
C1—H10.9500C21—H211.0000
C2—C31.4419 (16)C22—C231.552 (2)
C2—C181.4583 (16)C22—H22A0.9900
C3—C41.4042 (16)C22—H22B0.9900
C3—C81.4185 (15)C23—N21.483 (2)
C4—C51.3784 (16)C23—H23A0.9900
C4—H40.9500C23—H23B0.9900
C5—C61.4100 (15)N2—C241.484 (2)
C5—H50.9500C24—C251.545 (2)
C6—C71.3890 (16)C24—H24A0.9900
C6—C91.4819 (16)C24—H24B0.9900
C7—C81.3907 (16)C25—H25A0.9900
C7—H70.9500C25—H25B0.9900
C10—H10A0.9800C19'—N2'1.473 (13)
C10—H10B0.9800C19'—C20'1.532 (14)
C10—H10C0.9800C20'—O1'1.410 (14)
C11—C121.5245 (17)C20'—C21'1.525 (16)
C11—H11A0.9900C20'—H20'1.0000
C11—H11B0.9900O1'—H1'0.8400
C12—C171.3894 (17)C21'—C22'1.530 (16)
C12—C131.3924 (17)C21'—C25'1.534 (16)
C13—C141.3871 (19)C21'—H21'1.0000
C13—H130.9500C22'—C23'1.511 (15)
C14—C151.386 (2)C22'—H22C0.9900
C14—H140.9500C22'—H22D0.9900
C15—C161.382 (2)C23'—N2'1.474 (14)
C15—H150.9500C23'—H23C0.9900
C16—C171.3906 (18)C23'—H23D0.9900
C16—H160.9500N2'—C24'1.449 (14)
C17—H170.9500C24'—C25'1.552 (15)
C18—C19'1.317 (11)C24'—H24C0.9900
C18—C191.3414 (18)C24'—H24D0.9900
C18—H180.9500C25'—H25C0.9900
C19—N21.4473 (17)C25'—H25D0.9900
C1—N1—C8108.58 (10)C25—C21—C20107.91 (15)
C1—N1—C11125.67 (10)C22—C21—C20108.15 (13)
C8—N1—C11124.84 (10)C25—C21—H21110.5
C9—O3—C10116.16 (9)C22—C21—H21110.5
C2—C1—N1110.67 (11)C20—C21—H21110.5
C2—C1—H1124.7C21—C22—C23108.31 (12)
N1—C1—H1124.7C21—C22—H22A110.0
C1—C2—C3105.81 (10)C23—C22—H22A110.0
C1—C2—C18129.80 (11)C21—C22—H22B110.0
C3—C2—C18124.28 (11)C23—C22—H22B110.0
C4—C3—C8118.63 (10)H22A—C22—H22B108.4
C4—C3—C2134.05 (11)N2—C23—C22110.86 (12)
C8—C3—C2107.24 (10)N2—C23—H23A109.5
C5—C4—C3119.14 (10)C22—C23—H23A109.5
C5—C4—H4120.4N2—C23—H23B109.5
C3—C4—H4120.4C22—C23—H23B109.5
C4—C5—C6121.22 (11)H23A—C23—H23B108.1
C4—C5—H5119.4C19—N2—C23107.06 (13)
C6—C5—H5119.4C19—N2—C24109.12 (13)
C7—C6—C5121.04 (10)C23—N2—C24108.13 (12)
C7—C6—C9117.76 (10)N2—C24—C25112.14 (12)
C5—C6—C9121.20 (10)N2—C24—H24A109.2
C6—C7—C8117.38 (10)C25—C24—H24A109.2
C6—C7—H7121.3N2—C24—H24B109.2
C8—C7—H7121.3C25—C24—H24B109.2
N1—C8—C7129.70 (10)H24A—C24—H24B107.9
N1—C8—C3107.67 (10)C21—C25—C24107.59 (12)
C7—C8—C3122.56 (11)C21—C25—H25A110.2
O2—C9—O3123.10 (11)C24—C25—H25A110.2
O2—C9—C6124.16 (11)C21—C25—H25B110.2
O3—C9—C6112.74 (9)C24—C25—H25B110.2
O3—C10—H10A109.5H25A—C25—H25B108.5
O3—C10—H10B109.5C18—C19'—N2'123.0 (10)
H10A—C10—H10B109.5C18—C19'—C20'123.3 (9)
O3—C10—H10C109.5N2'—C19'—C20'112.0 (9)
H10A—C10—H10C109.5O1'—C20'—C21'114.7 (13)
H10B—C10—H10C109.5O1'—C20'—C19'108.5 (11)
N1—C11—C12113.36 (10)C21'—C20'—C19'107.0 (12)
N1—C11—H11A108.9O1'—C20'—H20'108.8
C12—C11—H11A108.9C21'—C20'—H20'108.8
N1—C11—H11B108.9C19'—C20'—H20'108.8
C12—C11—H11B108.9C20'—O1'—H1'109.5
H11A—C11—H11B107.7C20'—C21'—C22'106.2 (13)
C17—C12—C13118.55 (11)C20'—C21'—C25'108.6 (14)
C17—C12—C11121.83 (11)C22'—C21'—C25'109.8 (14)
C13—C12—C11119.62 (11)C20'—C21'—H21'110.7
C14—C13—C12120.72 (12)C22'—C21'—H21'110.7
C14—C13—H13119.6C25'—C21'—H21'110.7
C12—C13—H13119.6C23'—C22'—C21'104.9 (12)
C15—C14—C13120.31 (12)C23'—C22'—H22C110.8
C15—C14—H14119.8C21'—C22'—H22C110.8
C13—C14—H14119.8C23'—C22'—H22D110.8
C16—C15—C14119.39 (12)C21'—C22'—H22D110.8
C16—C15—H15120.3H22C—C22'—H22D108.8
C14—C15—H15120.3N2'—C23'—C22'116.0 (12)
C15—C16—C17120.38 (13)N2'—C23'—H23C108.3
C15—C16—H16119.8C22'—C23'—H23C108.3
C17—C16—H16119.8N2'—C23'—H23D108.3
C12—C17—C16120.65 (12)C22'—C23'—H23D108.3
C12—C17—H17119.7H23C—C23'—H23D107.4
C16—C17—H17119.7C24'—N2'—C23'107.8 (12)
C19'—C18—C2123.8 (5)C24'—N2'—C19'104.4 (11)
C19—C18—C2128.40 (12)C23'—N2'—C19'105.6 (11)
C19'—C18—H18115.1N2'—C24'—C25'113.8 (11)
C19—C18—H18115.8N2'—C24'—H24C108.8
C2—C18—H18115.8C25'—C24'—H24C108.8
C18—C19—N2122.23 (12)N2'—C24'—H24D108.8
C18—C19—C20123.71 (12)C25'—C24'—H24D108.8
N2—C19—C20113.72 (11)H24C—C24'—H24D107.7
O1—C20—C19109.43 (11)C21'—C25'—C24'106.2 (12)
O1—C20—C21112.52 (13)C21'—C25'—H25C110.5
C19—C20—C21106.93 (11)C24'—C25'—H25C110.5
O1—C20—H20109.3C21'—C25'—H25D110.5
C19—C20—H20109.3C24'—C25'—H25D110.5
C21—C20—H20109.3H25C—C25'—H25D108.7
C25—C21—C22109.07 (13)
C8—N1—C1—C21.61 (13)C2—C18—C19—C20175.48 (13)
C11—N1—C1—C2171.05 (10)C18—C19—C20—O135.0 (2)
N1—C1—C2—C30.62 (13)N2—C19—C20—O1138.42 (14)
N1—C1—C2—C18176.88 (11)C18—C19—C20—C21157.16 (17)
C1—C2—C3—C4177.33 (12)N2—C19—C20—C2116.29 (19)
C18—C2—C3—C40.8 (2)O1—C20—C21—C25171.58 (11)
C1—C2—C3—C80.56 (12)C19—C20—C21—C2568.25 (16)
C18—C2—C3—C8175.96 (10)O1—C20—C21—C2270.56 (15)
C8—C3—C4—C50.38 (16)C19—C20—C21—C2249.60 (17)
C2—C3—C4—C5176.11 (12)C25—C21—C22—C2351.32 (16)
C3—C4—C5—C60.94 (17)C20—C21—C22—C2365.79 (16)
C4—C5—C6—C71.10 (17)C21—C22—C23—N213.47 (17)
C4—C5—C6—C9178.01 (11)C18—C19—N2—C23104.06 (18)
C5—C6—C7—C80.11 (16)C20—C19—N2—C2369.50 (18)
C9—C6—C7—C8179.26 (10)C18—C19—N2—C24139.14 (17)
C1—N1—C8—C7175.07 (12)C20—C19—N2—C2447.30 (18)
C11—N1—C8—C75.52 (19)C22—C23—N2—C1950.65 (16)
C1—N1—C8—C31.92 (12)C22—C23—N2—C2466.81 (15)
C11—N1—C8—C3171.47 (10)C19—N2—C24—C2564.01 (16)
C6—C7—C8—N1178.07 (11)C23—N2—C24—C2552.12 (16)
C6—C7—C8—C31.47 (16)C22—C21—C25—C2465.38 (16)
C4—C3—C8—N1178.88 (10)C20—C21—C25—C2451.89 (16)
C2—C3—C8—N11.52 (12)N2—C24—C25—C2112.01 (18)
C4—C3—C8—C71.63 (17)C19—C18—C19'—N2'82.4 (17)
C2—C3—C8—C7175.73 (10)C2—C18—C19'—N2'27.3 (16)
C10—O3—C9—O20.86 (16)C19—C18—C19'—C20'81.5 (17)
C10—O3—C9—C6178.94 (9)C2—C18—C19'—C20'168.7 (10)
C7—C6—C9—O21.15 (17)C18—C19'—C20'—O1'16.1 (19)
C5—C6—C9—O2177.99 (11)N2'—C19'—C20'—O1'149.4 (13)
C7—C6—C9—O3178.65 (10)C18—C19'—C20'—C21'140.4 (14)
C5—C6—C9—O32.21 (15)N2'—C19'—C20'—C21'25.1 (17)
C1—N1—C11—C1298.55 (13)O1'—C20'—C21'—C22'165.5 (13)
C8—N1—C11—C1269.23 (14)C19'—C20'—C21'—C22'74.1 (15)
N1—C11—C12—C178.29 (16)O1'—C20'—C21'—C25'76.4 (17)
N1—C11—C12—C13171.63 (11)C19'—C20'—C21'—C25'44.0 (16)
C17—C12—C13—C140.46 (19)C20'—C21'—C22'—C23'48.1 (17)
C11—C12—C13—C14179.46 (12)C25'—C21'—C22'—C23'69.2 (17)
C12—C13—C14—C150.7 (2)C21'—C22'—C23'—N2'21 (2)
C13—C14—C15—C160.3 (2)C22'—C23'—N2'—C24'42.2 (18)
C14—C15—C16—C170.3 (2)C22'—C23'—N2'—C19'68.9 (17)
C13—C12—C17—C160.21 (19)C18—C19'—N2'—C24'92.0 (15)
C11—C12—C17—C16179.87 (12)C20'—C19'—N2'—C24'73.5 (15)
C15—C16—C17—C120.6 (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—C195.1 (2)C19'—N2'—C24'—C25'47.2 (16)
C3—C2—C18—C19170.57 (14)C20'—C21'—C25'—C24'67.2 (16)
C19'—C18—C19—N283.7 (14)C22'—C21'—C25'—C24'48.5 (17)
C2—C18—C19—N22.6 (2)N2'—C24'—C25'—C21'18.4 (18)
C19'—C18—C19—C2089.2 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O2i0.841.972.7989 (13)169
Symmetry code: (i) x1, y1, z.

Experimental details

Crystal data
Chemical formulaC25H26N2O3
Mr402.48
Crystal system, space groupTriclinic, 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)
V3)1006.04 (3)
Z2
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.28 × 0.22 × 0.12
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
9126, 4597, 3831
Rint0.024
(sin θ/λ)max1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.102, 1.04
No. of reflections4597
No. of parameters312
No. of restraints64
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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.

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O2i0.841.972.7989 (13)169.4
Symmetry code: (i) x1, y1, z.
 

Acknowledgements

This investigation was supported by NIH/National Cancer Institute grant PO1 CA140409.

References

First citationAmudhan, V., Reddy, Y. T., Sonar, V. N., Venkatraj, M., Crooks, P. A., Michael, L., Freeman, M. L. & Sekhar, K. R. (2010). Bioorg. Med. Chem. Lett. 20, 7323–7326.  Web of Science PubMed
First citationNonius (1998). COLLECT. Nonius, BV, Delft, The Netherlands.
First citationOtwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307–326. New York: Academic Press.
First citationSekhar, K. R., Crooks, P. A., Sonar, V. N., Friedman, D. B., Chan, J. Y., Meredith, M. J., Stames, J. H., Kelton, K. R., Summar, S. R., Sasi, S. & Freeman, M. L. (2003). Cancer Res. 63, 5636–5645.  Web of Science PubMed CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSonar, V. N., Parkin, S. & Crooks, P. A. (2004). Acta Cryst. C60, o659–o661.  Web of Science CSD CrossRef CAS IUCr Journals
First citationSonar, V. N., Reddy, Y. T., Sekhar, K. R., Sowmya, S., Freeman, M. L. & Crooks, P. A. (2007). Bioorg. Med. Chem. Lett. 17(24), 6821–6824.  Web of Science CrossRef

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