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

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ISSN: 2056-9890

5-Butyl­amino-2-[2-(di­methyl­amino)eth­yl]-1H-benz[de]iso­quinoline-1,3(2H)-dione

aInstitute of Molecular Medicine, Huaqiao University, Quanzhou, Fujian 362021, People's Republic of China.
*Correspondence e-mail: xielijuan@hqu.edu.cn

(Received 20 April 2010; accepted 19 May 2010; online 26 May 2010)

The title compound, C20H25N3O2, is a new amonafide analogue, which exhibits anti­tumor activity. The asymmetric unit contains two mol­ecules with similar conformations for the substituted aliphatic chains. The two independent mol­ecules form dmers through N—H⋯N hydrogen bonds. The crystal structure is stabilized via ππ stacking inter­actions, the shortest centroid–centroid separation between six-membered rings being 3.673 (2) Å.

Related literature

For general background to amonafide and its anti­tumour activity, see: Braña et al. (1981[Braña, M. F., Sanz, A. M., Castellano, J. M., Roldan, C. M. & Roldan, C. (1981). Eur. J. Med. Chem. 16, 207-212.], 2001[Braña, M. F., Cacho, M., Gradillas, A., De Pascual-Teresa, B. & Ramos, A. (2001). Curr. Pharm. Des. 7, 1745-1780.]); Braña & Ramos (2001[Braña, M. F. & Ramos, A. (2001). Curr. Med. Chem. Anti-Cancer Agents, 1, 237-255.]); Ratain et al. (1991[Ratain, M. J., Mick, R., Berezin, F., Janisch, L., Schilsky, R. L., Williams, S. F. & Smiddy, J. (1991). Clin. Pharmacol. Ther. 50, 573-579.], 1993[Ratain, M. J., Mick, R., Berezin, F., Janisch, L., Schilsky, R. L., Vogelzang, N. J. & Lane, L. B. (1993). Cancer Res. 53, 2304-2308.]). For the synthesis of amonafide analogues, see: Xie et al. (2009[Xie, L., Xu, Y., Wang, F., Liu, J., Qian, X. & Cui, J. (2009). Bioorg. Med. Chem. 17, 804-810.]).

[Scheme 1]

Experimental

Crystal data
  • C20H25N3O2

  • Mr = 339.43

  • Triclinic, [P \overline 1]

  • a = 11.5978 (12) Å

  • b = 12.5362 (13) Å

  • c = 14.3721 (16) Å

  • α = 72.329 (2)°

  • β = 70.599 (2)°

  • γ = 70.759 (2)°

  • V = 1816.1 (3) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 293 K

  • 0.36 × 0.33 × 0.08 mm

Data collection
  • Bruker SMART APEX CCD area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2001[Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.739, Tmax = 1.000

  • 10049 measured reflections

  • 7018 independent reflections

  • 3025 reflections with I > 2σ(I)

  • Rint = 0.059

Refinement
  • R[F2 > 2σ(F2)] = 0.068

  • wR(F2) = 0.175

  • S = 0.86

  • 7018 reflections

  • 466 parameters

  • 3 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.34 e Å−3

  • Δρmin = −0.25 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2⋯N6 0.86 (2) 2.33 (2) 3.176 (5) 173 (3)
N5—H5⋯N3 0.85 (2) 2.37 (2) 3.220 (5) 172 (4)

Data collection: SMART (Bruker, 2001[Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2001[Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; 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: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

Amonafide (Braña et al., 1981, 2001; Braña & Ramos, 2001) was the first compound of the naphthalimide family that reached the clinical trial stage and exhibited excellent antitumour activity against advanced breast cancer. However, in the clinical studies, it was found that amonafide was easily metabolized to N-acetyl-amonafide by enzyme N-acetyltransferase, which caused a high-variable, unpredictable toxicity (Ratain et al., 1991, 1993). In order to reduce the unpredictable toxic effect of the amonafide, we synthesized a series of amonafide analogues (Xie et al., 2009) involved the title compound, which is being reported in this article.

The molecular structure of the title compound is shown in Fig. 1. The asymmetric unit contains two independent molecules, and it is observed that the butyl chains do not present the common all-trans conformation. This uncommon feature could be attributed to formation of intermolecular N—H···N hydrogen bonds in the asymmetric unit [N2··· N6 and N3···N5], which involve the butyl and the dimethylamino groups, and reduce the intermolecular hindrance. The crystal structure is stabilized via π-π stacking interactions [centroid-centroid separations: 3.673 (2) and 3.693 (2) Å] and intermolecular N—H···N hydrogen bonds, which lead to a supramolecular network of stacked molecules in 1D chains (Fig. 2). Apart from the functional groups butylamino and N,N-dimethylamino-ethylamino, the central 1,8-naphthalimide fused rings system is almost planar.

Related literature top

For general background to amonafide and its antitumour activity, see: Braña et al. (1981, 2001); Braña & Ramos (2001); Ratain et al. (1991, 1993). For the synthesis of amonafide analogues, see: Xie et al. (2009).

Experimental top

A mixture of 3-bromide-1,8-naphthalic anhydride (277 mg, 1.0 mmol) and N,N-dimethylethyldiamine (92 mg, 1.0 mmol) was refluxed in EtOH (15 ml) for 2 h, to give the intermediate 5-bromo-2-[2-(dimethylamino)ethyl]-1H-benz[de]isoquinoline-1,3(2H)-dione. This intermediate (174 mg, 0.5 mmol), CuI (9 mg, 0.05 mmol), proline (11 mg, 0.1 mmol), Cs2CO3 (244 mg, 0.75 mmol) and n-butylamine (0.75 mmol) in dry DMSO (2 ml) were mixed and stirred at 383 K for 9 h under nitrogen. The crude products were purified by chromatography on silica gel with a mixture of CH2Cl2 and MeOH as eluent. Single crystals of the title compound were obtained from a CH2Cl2—MeOH solution.

Refinement top

C-bonded H atoms were positioned geometrically and refined as riding atoms, with C—H = 0.93 (aromatic), 0.97 (methylene) or 0.96 Å (methyl). Isotropic displacement parameters were computed as Uiso(H) = 1.2Ueq(carrier C) for methylene and aromatic H atoms, and Uiso(H) = 1.5Ueq(carrier C) for methyl groups. Amine H atoms H2 and H5 were found in a difference map and refined freely.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); 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: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The structure of the title compound showing 30% probability displacement ellipsoids and the atom labeling scheme. H atoms are omitted for clarity.
[Figure 2] Fig. 2. Packing diagram with H bonds indicated by dashed lines.
5-Butylamino-2-[2-(dimethylamino)ethyl]-1H-benz[de]isoquinoline- 1,3(2H)-dione top
Crystal data top
C20H25N3O2Z = 4
Mr = 339.43F(000) = 728
Triclinic, P1Dx = 1.241 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 11.5978 (12) ÅCell parameters from 1325 reflections
b = 12.5362 (13) Åθ = 5.2–49.0°
c = 14.3721 (16) ŵ = 0.08 mm1
α = 72.329 (2)°T = 293 K
β = 70.599 (2)°Prismatic, yellow
γ = 70.759 (2)°0.36 × 0.33 × 0.08 mm
V = 1816.1 (3) Å3
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
7018 independent reflections
Radiation source: fine-focus sealed tube3025 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.059
ϕ and ω scansθmax = 26.0°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
h = 1413
Tmin = 0.739, Tmax = 1.000k = 1511
10049 measured reflectionsl = 1716
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)] = 0.068H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.175 w = 1/[σ2(Fo2) + (0.0653P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.86(Δ/σ)max < 0.001
7018 reflectionsΔρmax = 0.34 e Å3
466 parametersΔρmin = 0.25 e Å3
3 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 constraintsExtinction coefficient: 0.0040 (10)
Primary atom site location: structure-invariant direct methods
Crystal data top
C20H25N3O2γ = 70.759 (2)°
Mr = 339.43V = 1816.1 (3) Å3
Triclinic, P1Z = 4
a = 11.5978 (12) ÅMo Kα radiation
b = 12.5362 (13) ŵ = 0.08 mm1
c = 14.3721 (16) ÅT = 293 K
α = 72.329 (2)°0.36 × 0.33 × 0.08 mm
β = 70.599 (2)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
7018 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)
3025 reflections with I > 2σ(I)
Tmin = 0.739, Tmax = 1.000Rint = 0.059
10049 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0683 restraints
wR(F2) = 0.175H atoms treated by a mixture of independent and constrained refinement
S = 0.86Δρmax = 0.34 e Å3
7018 reflectionsΔρmin = 0.25 e Å3
466 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.6424 (3)0.8935 (2)0.2061 (2)0.0695 (9)
O20.4583 (2)0.7887 (2)0.54144 (19)0.0625 (8)
O30.8585 (3)0.6222 (3)0.8127 (2)0.0754 (9)
O40.6754 (3)0.5191 (3)0.6307 (2)0.0700 (9)
N10.5553 (3)0.8357 (3)0.3739 (2)0.0481 (8)
N20.6845 (3)0.9030 (3)0.7247 (3)0.0592 (10)
N30.6185 (3)0.6109 (3)0.2983 (2)0.0537 (9)
N40.7643 (3)0.5748 (3)0.7207 (2)0.0518 (8)
N50.8927 (4)0.6479 (3)0.2640 (3)0.0665 (11)
N60.5323 (3)0.7148 (3)0.8571 (2)0.0537 (9)
C10.6412 (4)0.8876 (3)0.2925 (3)0.0508 (10)
C20.5400 (4)0.8308 (3)0.4763 (3)0.0480 (10)
C30.6272 (3)0.8762 (3)0.4991 (3)0.0394 (9)
C40.7179 (3)0.9258 (3)0.4200 (3)0.0416 (9)
C50.7264 (3)0.9327 (3)0.3189 (3)0.0461 (10)
C60.8156 (4)0.9811 (3)0.2421 (3)0.0563 (11)
H60.82120.98550.17500.068*
C70.8974 (4)1.0234 (4)0.2660 (3)0.0628 (12)
H70.95731.05630.21440.075*
C80.8902 (3)1.0169 (3)0.3642 (3)0.0578 (11)
H80.94581.04520.37840.069*
C90.8004 (3)0.9683 (3)0.4447 (3)0.0453 (10)
C100.7902 (3)0.9603 (3)0.5474 (3)0.0510 (10)
H100.84390.98900.56350.061*
C110.7023 (3)0.9107 (3)0.6237 (3)0.0453 (10)
C120.6205 (3)0.8696 (3)0.5963 (3)0.0455 (10)
H120.55990.83680.64720.055*
C130.7608 (4)0.9397 (4)0.7643 (3)0.0675 (13)
H13A0.77531.01370.72320.081*
H13B0.84220.88370.76180.081*
C140.6929 (5)0.9512 (5)0.8749 (3)0.108 (2)
H14A0.60630.99570.87750.130*
H14B0.69030.87440.91630.130*
C150.7481 (6)1.0049 (6)0.9201 (4)0.123 (2)
H15A0.83360.95850.92020.148*
H15B0.70031.00240.99010.148*
C160.7529 (6)1.1257 (5)0.8708 (4)0.129 (2)
H16A0.80981.12820.80460.194*
H16B0.78211.15570.91050.194*
H16C0.67001.17180.86540.194*
C170.4680 (4)0.7897 (3)0.3524 (3)0.0567 (11)
H17A0.46490.82240.28250.068*
H17B0.38380.81450.39480.068*
C180.5044 (4)0.6589 (3)0.3698 (3)0.0572 (11)
H18A0.51620.62660.43750.069*
H18B0.43490.63450.36670.069*
C190.6511 (4)0.4846 (4)0.3333 (3)0.0811 (14)
H19A0.58350.45510.33540.122*
H19B0.66400.46490.39970.122*
H19C0.72710.45130.28770.122*
C200.5971 (4)0.6400 (4)0.1975 (3)0.0798 (14)
H20A0.52410.61670.20200.120*
H20B0.66970.60040.15320.120*
H20C0.58350.72210.17140.120*
C210.8560 (4)0.6183 (4)0.7304 (3)0.0565 (11)
C220.7540 (4)0.5639 (3)0.6306 (3)0.0529 (11)
C230.8405 (3)0.6098 (3)0.5360 (3)0.0464 (10)
C240.9353 (3)0.6535 (3)0.5412 (3)0.0468 (10)
C250.9461 (3)0.6572 (3)0.6348 (3)0.0524 (11)
C261.0414 (4)0.6991 (4)0.6382 (3)0.0631 (12)
H261.04810.70280.69980.076*
C271.1271 (4)0.7359 (4)0.5481 (4)0.0669 (13)
H271.19130.76310.55050.080*
C281.1178 (4)0.7325 (4)0.4568 (3)0.0646 (12)
H281.17610.75700.39810.078*
C291.0213 (3)0.6923 (3)0.4503 (3)0.0508 (10)
C301.0069 (4)0.6899 (3)0.3573 (3)0.0580 (11)
H301.06360.71500.29760.070*
C310.9108 (4)0.6512 (3)0.3526 (3)0.0520 (10)
C320.8288 (3)0.6093 (3)0.4460 (3)0.0513 (10)
H320.76510.58070.44470.062*
C330.9693 (4)0.6911 (4)0.1663 (3)0.0804 (15)
H33A1.05760.65330.16360.097*
H33B0.95760.77340.15760.097*
C340.9377 (6)0.6714 (5)0.0831 (4)0.119 (2)
H34A0.84940.70990.08610.142*
H34B0.94780.58910.09310.142*
C351.0166 (7)0.7137 (6)0.0212 (4)0.157 (3)
H35A0.96360.74210.06800.188*
H35B1.04360.77850.01960.188*
C361.1246 (7)0.6296 (7)0.0586 (6)0.207 (4)
H36A1.19440.62930.03670.310*
H36B1.14530.64760.13110.310*
H36C1.10750.55460.03340.310*
C370.6757 (4)0.5292 (3)0.8135 (3)0.0606 (12)
H37A0.70800.51700.87110.073*
H37B0.67160.45460.80960.073*
C380.5425 (4)0.6093 (4)0.8305 (3)0.0581 (11)
H38A0.51460.62910.76940.070*
H38B0.48580.56770.88400.070*
C390.4064 (4)0.7929 (4)0.8558 (3)0.0811 (15)
H39A0.38980.80270.79210.122*
H39B0.40330.86670.86480.122*
H39C0.34380.76040.90950.122*
C400.5512 (4)0.6922 (4)0.9577 (3)0.0810 (15)
H40A0.53680.76440.97540.121*
H40B0.63620.64760.95760.121*
H40C0.49300.64991.00620.121*
H20.649 (3)0.850 (3)0.763 (2)0.065 (14)*
H50.818 (3)0.645 (4)0.271 (3)0.082 (17)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.087 (2)0.081 (2)0.0454 (18)0.0301 (18)0.0225 (16)0.0058 (15)
O20.0622 (18)0.076 (2)0.0559 (18)0.0390 (17)0.0017 (14)0.0159 (15)
O30.075 (2)0.097 (3)0.059 (2)0.0247 (19)0.0253 (17)0.0121 (17)
O40.0651 (19)0.080 (2)0.073 (2)0.0406 (18)0.0019 (15)0.0221 (16)
N10.0513 (19)0.042 (2)0.054 (2)0.0131 (16)0.0176 (16)0.0100 (16)
N20.070 (2)0.063 (3)0.052 (2)0.032 (2)0.0168 (19)0.0054 (19)
N30.058 (2)0.054 (2)0.053 (2)0.0076 (18)0.0205 (17)0.0165 (17)
N40.049 (2)0.050 (2)0.050 (2)0.0138 (17)0.0090 (16)0.0056 (16)
N50.068 (3)0.079 (3)0.051 (2)0.025 (2)0.010 (2)0.0106 (19)
N60.057 (2)0.050 (2)0.048 (2)0.0141 (18)0.0105 (16)0.0056 (16)
C10.055 (2)0.042 (2)0.051 (3)0.009 (2)0.016 (2)0.005 (2)
C20.048 (2)0.040 (2)0.054 (3)0.012 (2)0.011 (2)0.0103 (19)
C30.040 (2)0.030 (2)0.045 (2)0.0054 (17)0.0114 (17)0.0080 (17)
C40.040 (2)0.031 (2)0.047 (2)0.0052 (17)0.0103 (18)0.0046 (17)
C50.047 (2)0.038 (2)0.048 (2)0.0086 (19)0.0135 (19)0.0034 (18)
C60.057 (3)0.057 (3)0.044 (2)0.015 (2)0.009 (2)0.001 (2)
C70.051 (3)0.063 (3)0.063 (3)0.025 (2)0.006 (2)0.004 (2)
C80.052 (3)0.058 (3)0.061 (3)0.022 (2)0.013 (2)0.003 (2)
C90.041 (2)0.037 (2)0.052 (2)0.0097 (18)0.0105 (19)0.0048 (18)
C100.051 (2)0.045 (3)0.061 (3)0.013 (2)0.020 (2)0.010 (2)
C110.048 (2)0.040 (2)0.047 (2)0.0108 (19)0.0140 (19)0.0057 (18)
C120.043 (2)0.038 (2)0.051 (2)0.0127 (19)0.0055 (18)0.0070 (18)
C130.080 (3)0.073 (3)0.061 (3)0.033 (3)0.026 (2)0.008 (2)
C140.153 (5)0.167 (6)0.049 (3)0.115 (5)0.034 (3)0.005 (3)
C150.160 (6)0.143 (6)0.069 (4)0.065 (5)0.007 (4)0.024 (4)
C160.165 (6)0.123 (6)0.108 (5)0.057 (5)0.010 (4)0.044 (4)
C170.053 (2)0.061 (3)0.065 (3)0.012 (2)0.022 (2)0.021 (2)
C180.062 (3)0.060 (3)0.060 (3)0.024 (2)0.018 (2)0.016 (2)
C190.086 (3)0.062 (3)0.097 (4)0.006 (3)0.037 (3)0.021 (3)
C200.091 (3)0.094 (4)0.065 (3)0.016 (3)0.031 (3)0.029 (3)
C210.048 (2)0.051 (3)0.066 (3)0.006 (2)0.020 (2)0.007 (2)
C220.045 (2)0.047 (3)0.064 (3)0.012 (2)0.008 (2)0.014 (2)
C230.041 (2)0.039 (2)0.054 (3)0.0058 (19)0.0110 (19)0.0098 (19)
C240.039 (2)0.033 (2)0.061 (3)0.0009 (18)0.016 (2)0.0060 (19)
C250.043 (2)0.039 (2)0.070 (3)0.004 (2)0.020 (2)0.005 (2)
C260.055 (3)0.057 (3)0.079 (3)0.011 (2)0.031 (2)0.006 (2)
C270.048 (3)0.060 (3)0.090 (4)0.018 (2)0.022 (3)0.004 (3)
C280.048 (3)0.057 (3)0.078 (3)0.015 (2)0.015 (2)0.001 (2)
C290.040 (2)0.038 (2)0.066 (3)0.0065 (19)0.013 (2)0.004 (2)
C300.045 (2)0.049 (3)0.064 (3)0.008 (2)0.006 (2)0.003 (2)
C310.050 (2)0.036 (2)0.060 (3)0.006 (2)0.012 (2)0.004 (2)
C320.044 (2)0.043 (2)0.067 (3)0.012 (2)0.011 (2)0.014 (2)
C330.080 (3)0.082 (4)0.062 (3)0.021 (3)0.005 (3)0.006 (3)
C340.163 (6)0.124 (5)0.058 (3)0.052 (5)0.001 (4)0.018 (3)
C350.190 (7)0.125 (6)0.086 (5)0.025 (6)0.024 (5)0.009 (4)
C360.196 (9)0.188 (9)0.203 (8)0.089 (7)0.074 (7)0.090 (7)
C370.063 (3)0.053 (3)0.057 (3)0.019 (2)0.010 (2)0.001 (2)
C380.055 (3)0.063 (3)0.052 (3)0.025 (2)0.005 (2)0.005 (2)
C390.064 (3)0.074 (4)0.080 (3)0.011 (3)0.000 (3)0.009 (3)
C400.103 (4)0.092 (4)0.048 (3)0.034 (3)0.016 (3)0.009 (2)
Geometric parameters (Å, º) top
O1—C11.216 (4)C17—C181.515 (5)
O2—C21.222 (4)C17—H17A0.9700
O3—C211.209 (4)C17—H17B0.9700
O4—C221.218 (4)C18—H18A0.9700
N1—C21.406 (4)C18—H18B0.9700
N1—C11.406 (4)C19—H19A0.9600
N1—C171.469 (4)C19—H19B0.9600
N2—C111.375 (4)C19—H19C0.9600
N2—C131.442 (5)C20—H20A0.9600
N2—H20.86 (2)C20—H20B0.9600
N3—C181.455 (5)C20—H20C0.9600
N3—C201.466 (4)C21—C251.481 (5)
N3—C191.466 (5)C22—C231.478 (5)
N4—C221.391 (5)C23—C321.347 (5)
N4—C211.404 (5)C23—C241.411 (5)
N4—C371.475 (4)C24—C251.407 (5)
N5—C311.372 (5)C24—C291.417 (5)
N5—C331.443 (5)C25—C261.391 (5)
N5—H50.85 (2)C26—C271.400 (5)
N6—C381.444 (5)C26—H260.9300
N6—C401.463 (4)C27—C281.366 (5)
N6—C391.468 (5)C27—H270.9300
C1—C51.480 (5)C28—C291.409 (5)
C2—C31.473 (5)C28—H280.9300
C3—C121.351 (4)C29—C301.410 (5)
C3—C41.412 (4)C30—C311.382 (5)
C4—C51.401 (5)C30—H300.9300
C4—C91.415 (5)C31—C321.426 (5)
C5—C61.380 (5)C32—H320.9300
C6—C71.400 (5)C33—C341.467 (6)
C6—H60.9300C33—H33A0.9700
C7—C81.365 (5)C33—H33B0.9700
C7—H70.9300C34—C351.514 (7)
C8—C91.408 (5)C34—H34A0.9700
C8—H80.9300C34—H34B0.9700
C9—C101.416 (5)C35—C361.413 (8)
C10—C111.375 (5)C35—H35A0.9700
C10—H100.9300C35—H35B0.9700
C11—C121.419 (5)C36—H36A0.9600
C12—H120.9300C36—H36B0.9600
C13—C141.550 (6)C36—H36C0.9600
C13—H13A0.9700C37—C381.527 (5)
C13—H13B0.9700C37—H37A0.9700
C14—C151.453 (7)C37—H37B0.9700
C14—H14A0.9700C38—H38A0.9700
C14—H14B0.9700C38—H38B0.9700
C15—C161.476 (7)C39—H39A0.9600
C15—H15A0.9700C39—H39B0.9600
C15—H15B0.9700C39—H39C0.9600
C16—H16A0.9600C40—H40A0.9600
C16—H16B0.9600C40—H40B0.9600
C16—H16C0.9600C40—H40C0.9600
C2—N1—C1124.9 (3)N3—C19—H19C109.5
C2—N1—C17116.3 (3)H19A—C19—H19C109.5
C1—N1—C17118.7 (3)H19B—C19—H19C109.5
C11—N2—C13124.1 (3)N3—C20—H20A109.5
C11—N2—H2113 (3)N3—C20—H20B109.5
C13—N2—H2118 (3)H20A—C20—H20B109.5
C18—N3—C20110.6 (3)N3—C20—H20C109.5
C18—N3—C19108.1 (3)H20A—C20—H20C109.5
C20—N3—C19109.0 (3)H20B—C20—H20C109.5
C22—N4—C21125.5 (3)O3—C21—N4120.5 (4)
C22—N4—C37115.9 (3)O3—C21—C25123.8 (4)
C21—N4—C37118.4 (3)N4—C21—C25115.7 (4)
C31—N5—C33122.4 (4)O4—C22—N4120.6 (4)
C31—N5—H5113 (3)O4—C22—C23122.0 (4)
C33—N5—H5120 (3)N4—C22—C23117.4 (4)
C38—N6—C40111.6 (3)C32—C23—C24120.6 (3)
C38—N6—C39109.5 (3)C32—C23—C22120.1 (4)
C40—N6—C39108.7 (3)C24—C23—C22119.3 (4)
O1—C1—N1120.0 (4)C25—C24—C23121.0 (3)
O1—C1—C5123.7 (4)C25—C24—C29120.2 (4)
N1—C1—C5116.3 (4)C23—C24—C29118.8 (4)
O2—C2—N1120.0 (4)C26—C25—C24120.0 (4)
O2—C2—C3123.2 (4)C26—C25—C21119.2 (4)
N1—C2—C3116.9 (3)C24—C25—C21120.8 (4)
C12—C3—C4120.1 (3)C25—C26—C27119.5 (4)
C12—C3—C2119.6 (3)C25—C26—H26120.3
C4—C3—C2120.3 (3)C27—C26—H26120.3
C5—C4—C3120.7 (3)C28—C27—C26121.1 (4)
C5—C4—C9120.5 (3)C28—C27—H27119.4
C3—C4—C9118.7 (3)C26—C27—H27119.4
C6—C5—C4120.3 (4)C27—C28—C29121.0 (4)
C6—C5—C1118.8 (4)C27—C28—H28119.5
C4—C5—C1120.9 (3)C29—C28—H28119.5
C5—C6—C7119.4 (4)C28—C29—C30122.7 (4)
C5—C6—H6120.3C28—C29—C24118.2 (4)
C7—C6—H6120.3C30—C29—C24119.1 (4)
C8—C7—C6120.7 (4)C31—C30—C29121.7 (4)
C8—C7—H7119.6C31—C30—H30119.1
C6—C7—H7119.6C29—C30—H30119.1
C7—C8—C9121.5 (4)N5—C31—C30123.8 (4)
C7—C8—H8119.2N5—C31—C32118.8 (4)
C9—C8—H8119.2C30—C31—C32117.4 (4)
C8—C9—C4117.5 (4)C23—C32—C31122.3 (4)
C8—C9—C10123.0 (4)C23—C32—H32118.8
C4—C9—C10119.6 (3)C31—C32—H32118.8
C11—C10—C9121.1 (4)N5—C33—C34112.5 (4)
C11—C10—H10119.5N5—C33—H33A109.1
C9—C10—H10119.5C34—C33—H33A109.1
C10—C11—N2124.3 (4)N5—C33—H33B109.1
C10—C11—C12118.0 (4)C34—C33—H33B109.1
N2—C11—C12117.7 (3)H33A—C33—H33B107.8
C3—C12—C11122.6 (3)C33—C34—C35114.7 (5)
C3—C12—H12118.7C33—C34—H34A108.6
C11—C12—H12118.7C35—C34—H34A108.6
N2—C13—C14109.9 (3)C33—C34—H34B108.6
N2—C13—H13A109.7C35—C34—H34B108.6
C14—C13—H13A109.7H34A—C34—H34B107.6
N2—C13—H13B109.7C36—C35—C34114.9 (6)
C14—C13—H13B109.7C36—C35—H35A108.5
H13A—C13—H13B108.2C34—C35—H35A108.5
C15—C14—C13116.4 (4)C36—C35—H35B108.5
C15—C14—H14A108.2C34—C35—H35B108.5
C13—C14—H14A108.2H35A—C35—H35B107.5
C15—C14—H14B108.2C35—C36—H36A109.5
C13—C14—H14B108.2C35—C36—H36B109.5
H14A—C14—H14B107.3H36A—C36—H36B109.5
C14—C15—C16116.1 (5)C35—C36—H36C109.5
C14—C15—H15A108.3H36A—C36—H36C109.5
C16—C15—H15A108.3H36B—C36—H36C109.5
C14—C15—H15B108.3N4—C37—C38113.2 (3)
C16—C15—H15B108.3N4—C37—H37A108.9
H15A—C15—H15B107.4C38—C37—H37A108.9
C15—C16—H16A109.5N4—C37—H37B108.9
C15—C16—H16B109.5C38—C37—H37B108.9
H16A—C16—H16B109.5H37A—C37—H37B107.8
C15—C16—H16C109.5N6—C38—C37114.1 (3)
H16A—C16—H16C109.5N6—C38—H38A108.7
H16B—C16—H16C109.5C37—C38—H38A108.7
N1—C17—C18113.6 (3)N6—C38—H38B108.7
N1—C17—H17A108.9C37—C38—H38B108.7
C18—C17—H17A108.9H38A—C38—H38B107.6
N1—C17—H17B108.9N6—C39—H39A109.5
C18—C17—H17B108.9N6—C39—H39B109.5
H17A—C17—H17B107.7H39A—C39—H39B109.5
N3—C18—C17114.7 (3)N6—C39—H39C109.5
N3—C18—H18A108.6H39A—C39—H39C109.5
C17—C18—H18A108.6H39B—C39—H39C109.5
N3—C18—H18B108.6N6—C40—H40A109.5
C17—C18—H18B108.6N6—C40—H40B109.5
H18A—C18—H18B107.6H40A—C40—H40B109.5
N3—C19—H19A109.5N6—C40—H40C109.5
N3—C19—H19B109.5H40A—C40—H40C109.5
H19A—C19—H19B109.5H40B—C40—H40C109.5
C2—N1—C1—O1175.7 (3)C22—N4—C21—O3178.5 (4)
C17—N1—C1—O10.1 (5)C37—N4—C21—O32.9 (6)
C2—N1—C1—C54.2 (5)C22—N4—C21—C251.3 (5)
C17—N1—C1—C5179.8 (3)C37—N4—C21—C25177.0 (3)
C1—N1—C2—O2176.4 (3)C21—N4—C22—O4175.8 (4)
C17—N1—C2—O20.8 (5)C37—N4—C22—O40.1 (5)
C1—N1—C2—C34.5 (5)C21—N4—C22—C234.9 (5)
C17—N1—C2—C3179.8 (3)C37—N4—C22—C23179.4 (3)
O2—C2—C3—C121.6 (5)O4—C22—C23—C324.1 (6)
N1—C2—C3—C12177.4 (3)N4—C22—C23—C32175.2 (3)
O2—C2—C3—C4178.8 (3)O4—C22—C23—C24175.7 (4)
N1—C2—C3—C42.2 (5)N4—C22—C23—C245.0 (5)
C12—C3—C4—C5179.6 (3)C32—C23—C24—C25178.3 (3)
C2—C3—C4—C50.0 (5)C22—C23—C24—C251.9 (5)
C12—C3—C4—C90.2 (5)C32—C23—C24—C292.7 (5)
C2—C3—C4—C9179.8 (3)C22—C23—C24—C29177.1 (3)
C3—C4—C5—C6179.8 (3)C23—C24—C25—C26179.1 (3)
C9—C4—C5—C60.0 (5)C29—C24—C25—C260.1 (5)
C3—C4—C5—C10.3 (5)C23—C24—C25—C211.8 (5)
C9—C4—C5—C1179.5 (3)C29—C24—C25—C21179.2 (3)
O1—C1—C5—C62.2 (6)O3—C21—C25—C261.1 (6)
N1—C1—C5—C6177.9 (3)N4—C21—C25—C26178.7 (3)
O1—C1—C5—C4178.3 (4)O3—C21—C25—C24178.0 (4)
N1—C1—C5—C41.6 (5)N4—C21—C25—C242.1 (5)
C4—C5—C6—C70.1 (6)C24—C25—C26—C271.0 (6)
C1—C5—C6—C7179.6 (3)C21—C25—C26—C27179.9 (4)
C5—C6—C7—C80.3 (6)C25—C26—C27—C280.8 (6)
C6—C7—C8—C90.4 (6)C26—C27—C28—C290.3 (6)
C7—C8—C9—C40.2 (6)C27—C28—C29—C30178.5 (4)
C7—C8—C9—C10179.9 (4)C27—C28—C29—C241.1 (6)
C5—C4—C9—C80.1 (5)C25—C24—C29—C280.9 (5)
C3—C4—C9—C8179.8 (3)C23—C24—C29—C28178.1 (3)
C5—C4—C9—C10179.9 (3)C25—C24—C29—C30178.8 (3)
C3—C4—C9—C100.1 (5)C23—C24—C29—C302.2 (5)
C8—C9—C10—C11179.1 (4)C28—C29—C30—C31179.4 (4)
C4—C9—C10—C110.7 (5)C24—C29—C30—C310.3 (6)
C9—C10—C11—N2178.0 (3)C33—N5—C31—C303.5 (6)
C9—C10—C11—C121.1 (5)C33—N5—C31—C32178.4 (4)
C13—N2—C11—C103.9 (6)C29—C30—C31—N5179.6 (4)
C13—N2—C11—C12179.2 (4)C29—C30—C31—C322.3 (6)
C4—C3—C12—C110.2 (5)C24—C23—C32—C310.6 (6)
C2—C3—C12—C11179.4 (3)C22—C23—C32—C31179.2 (3)
C10—C11—C12—C30.8 (5)N5—C31—C32—C23179.9 (4)
N2—C11—C12—C3178.0 (3)C30—C31—C32—C231.9 (6)
C11—N2—C13—C14164.1 (4)C31—N5—C33—C34176.3 (4)
N2—C13—C14—C15170.6 (5)N5—C33—C34—C35179.2 (5)
C13—C14—C15—C1661.5 (8)C33—C34—C35—C3693.2 (8)
C2—N1—C17—C1879.6 (4)C22—N4—C37—C3877.6 (4)
C1—N1—C17—C18104.4 (4)C21—N4—C37—C38106.3 (4)
C20—N3—C18—C1768.8 (4)C40—N6—C38—C3768.5 (4)
C19—N3—C18—C17172.0 (3)C39—N6—C38—C37171.0 (3)
N1—C17—C18—N369.1 (4)N4—C37—C38—N670.1 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···N60.86 (2)2.33 (2)3.176 (5)173 (3)
N5—H5···N30.85 (2)2.37 (2)3.220 (5)172 (4)

Experimental details

Crystal data
Chemical formulaC20H25N3O2
Mr339.43
Crystal system, space groupTriclinic, P1
Temperature (K)293
a, b, c (Å)11.5978 (12), 12.5362 (13), 14.3721 (16)
α, β, γ (°)72.329 (2), 70.599 (2), 70.759 (2)
V3)1816.1 (3)
Z4
Radiation typeMo Kα
µ (mm1)0.08
Crystal size (mm)0.36 × 0.33 × 0.08
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2001)
Tmin, Tmax0.739, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections
10049, 7018, 3025
Rint0.059
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.068, 0.175, 0.86
No. of reflections7018
No. of parameters466
No. of restraints3
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.34, 0.25

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···N60.86 (2)2.33 (2)3.176 (5)173 (3)
N5—H5···N30.85 (2)2.37 (2)3.220 (5)172 (4)
 

Footnotes

Other affiliation: State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, People's Republic of China

Acknowledgements

The author is grateful for the support of the Scientific Research Foundation of Huaqiao University (09BS406) and the State Key Laboratory of Oncology in South China.

References

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First citationBraña, M. F., Sanz, A. M., Castellano, J. M., Roldan, C. M. & Roldan, C. (1981). Eur. J. Med. Chem. 16, 207–212.
First citationBruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationRatain, M. J., Mick, R., Berezin, F., Janisch, L., Schilsky, R. L., Vogelzang, N. J. & Lane, L. B. (1993). Cancer Res. 53, 2304–2308.  CAS PubMed Web of Science
First citationRatain, M. J., Mick, R., Berezin, F., Janisch, L., Schilsky, R. L., Williams, S. F. & Smiddy, J. (1991). Clin. Pharmacol. Ther. 50, 573–579.  CrossRef PubMed CAS
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationXie, L., Xu, Y., Wang, F., Liu, J., Qian, X. & Cui, J. (2009). Bioorg. Med. Chem. 17, 804–810.  Web of Science CrossRef PubMed CAS

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