6-Isopropyl-3-phenyl-5-(p-tol­yloxy)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one: whole-mol­ecule disorder

Zeng, X.-H.; Deng, S.-H.; Chen, P.; Wang, H.-M.; Gao, H.-T.

doi:10.1107/S1600536809039798

organic compounds

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ISSN: 2056-9890

Volume 65| Part 11| November 2009| Pages o2653-o2654

https://doi.org/10.1107/S1600536809039798

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6-Isopropyl-3-phenyl-5-(p-tolyloxy)-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one: whole-molecule disorder

Xiao-Hua Zeng,^a,^b ^* Shou-Heng Deng,^b Ping Chen,^b Hong-Mei Wang ^a and Hai-Tao Gao ^a

^aInstitute of Medicinal Chemistry, Yunyang Medical College, Shiyan 442000, People's Republic of China, ^bCenter of Oncology, People's Hospital affiliated with Yunyang Medical College, Shiyan 442000, People's Republic of China, and ^cDepartment of Medicinal Chemistry, Yunyang Medical College, Shiyan 442000, People's Republic of China
^*Correspondence e-mail: zengken@126.com

(Received 10 September 2009; accepted 30 September 2009; online 7 October 2009)

The title compound, C₂₀H₁₉N₅O₂, exhibits whole-molecule disorder the refined ratios of the two components being 0.57 (2):0.43 (2). In the major component, the essentially planar [maximum deviation 0.033 (17) Å] fused pyrimidine and triazole ring system forms a dihedral angle of 10.5 (3)° with the phenyl ring, while in the minor component of disorder this angle is 27.5 (5)°. The crystal structure is stabilized by π–π stacking interactions between symmetry-related triazole and pyrimidine rings, with centroid–centroid distances of 3.594 (10) Å.

Related literature

For the biological activity of 8-azaguanine derivatives see: Roblin et al. (1945 ); Ding et al. (2004 ); Mitchell et al. (1950 ); Levine et al. (1963 ); Montgomery et al. (1962 )); Yamamoto et al. (1967 ); Bariana (1971 ); Holland et al. (1975 ). For related structures, see: Ferguson et al. (1998 ); Zhao, Xie et al. (2005 ); Zhao, Hu et al. (2005 ); Zhao, Wang & Ding (2005 ); Chen & Shi (2006 ); Maldonado et al. (2006 ); Xiao et al. (2007 ); Wang et al. (2006 , 2008 ); Zeng, Deng et al. (2009 ), Zeng, Liu et al. (2009 ). For examples of whole-molecule disorder, see: Kirsop et al. (2006 ); Cox & Wardell (2003 ). For the preparation, see: Zeng et al. (2006 ).

Experimental

Crystal data

C₂₀H₁₉N₅O₂
M_r = 361.40
Orthorhombic, C 222₁
a = 10.2335 (6) Å
b = 21.8532 (12) Å
c = 16.7441 (9) Å
V = 3744.6 (4) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.20 × 0.20 × 0.20 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: none
21260 measured reflections
2285 independent reflections
1790 reflections with I > 2σ(I)
R_int = 0.023

Refinement

R[F² > 2σ(F²)] = 0.050
wR(F²) = 0.144
S = 1.06
2285 reflections
446 parameters
15 restraints
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: SMART (Bruker, 2001 ); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009 ); software used to prepare material for publication: SHELXTL97 (Sheldrick, 2008).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536809039798/lh2904sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536809039798/lh2904Isup2.hkl

checkCIF report

Comment top

The derivatives of heterocycles containing the 8-azaguanine system, which are well known bioisosteres of guanine, are of great importance because of their remarkable biological properties. Some of these activities include antimicrobial or antifungal activities (Roblin et al., 1945; Ding et al., 2004), encephaloma cell inhibitor activity (Mitchell et al., 1950; Levine et al., 1963), antileukemie activity (Montgomery et al., 1962), hypersusceptibility inhibitor activity and acesodyne activity (Yamamoto et al., 1967; Bariana, 1971; Holland et al., 1975).

In recent years, we have been engaged in the preparation of the derivatives of 8-azaguanine via aza-Wittig reaction of beta-ethoxycarbonyl iminophosphorane with aromatic isocyanate (Zhao, Xie et al., 2005). As a continuation of our research for new biologically active heterocycles, the title compound, (I), was obtained from beta-ethoxycarbonyl iminophosphorane and alphalic isocyanate, and the crystal structure is reported herein.

The molecules of (I), which lie in general positions, exhibit 'whole molecule disorder' with the site-occupancy factors of 0.57 (2) and 0.43 (2), (Fig.1). The bond lengths and angles within the triazolopyrimidinone moiety are in good agreement with those observed for closely related structures. As reported for related compounds (Ferguson et al., 1998; Maldonado et al., 2006; Zeng, Deng et al., 2009; Zeng, Liu et al., 2009; Zhao, Hu et al., 2005; Zhao, Wang & Ding, 2005; Wang et al., 2006, 2008; Xiao et al., 2007; Chen & Shi, 2006), all ring atoms in the pyrimidine ring system are essentially coplanar (maximum deviation -0.033 (17) Å for atom N4), indicating that the moiety is a conjugate system.

There are no inter- or intra- molecular hydrogen bonding interactions. The molecular conformation and crystal packing are stabilized by π–π stacking interactions occurring between symmetry realted triazole and pyrimidine rings, with centroid-to-centroid distances of 3.594 (10) Å.

Related literature top

For the biological activity of 8-azaguanine derivatives see: Roblin et al. (1945); Ding et al. (2004); Mitchell et al. (1950); Levine et al. (1963); Montgomery et al. (1962)); Yamamoto et al. (1967); Bariana (1971); Holland et al. (1975). For related structures, see: Ferguson et al. (1998); Zhao, Xie et al. (2005); Zhao, Hu et al. (2005); Zhao, Wang & Ding (2005); Chen & Shi (2006); Maldonado et al. (2006); Xiao et al. (2007); Wang et al. (2006, 2008); Zeng, Deng et al. (2009), Zeng, Liu et al. (2009). For examples of whole-molecule disorder, see: Kirsop et al. (2006); Cox & Wardell (2003). For the preparation, see: Zeng et al. (2006).

Experimental top

To a solution of carbodiimide in CH₂Cl₂/CH₃CN (1:4 v/v, 15 ml) prepared according to the literature method (Zeng et al., 2006), was added p-cresol (3 mmol) and excess K₂CO₃. After the reaction mixture was stirred for 12 h. The solvent was removed under reduced pressure and the residue was recrystallized from EtOH to give the title compound (I) in yield of 85% (m.p. 436 K). Elemental analysis: calculated for C₂₀H₁₉N₅O₂: C, 66.47; H, 5.30; N, 19.38%. Found: C, 65.52; H, 5.63; N, 18.89%. Crystals suitable for singlecrystal X-ray diffraction were obtained from hexane and dichloromethane (1:3 v/v) at room temperature.

Structure description top

For the biological activity of 8-azaguanine derivatives see: Roblin et al. (1945); Ding et al. (2004); Mitchell et al. (1950); Levine et al. (1963); Montgomery et al. (1962)); Yamamoto et al. (1967); Bariana (1971); Holland et al. (1975). For related structures, see: Ferguson et al. (1998); Zhao, Xie et al. (2005); Zhao, Hu et al. (2005); Zhao, Wang & Ding (2005); Chen & Shi (2006); Maldonado et al. (2006); Xiao et al. (2007); Wang et al. (2006, 2008); Zeng, Deng et al. (2009), Zeng, Liu et al. (2009). For examples of whole-molecule disorder, see: Kirsop et al. (2006); Cox & Wardell (2003). For the preparation, see: Zeng et al. (2006).

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: PLATON (Spek, 2009); software used to prepare material for publication: SHELXTL97 (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Dashed lines indicate the minor component of disorder. H atoms have been omitted and displacement parameters are drawn at the 50% probability level.

6-Isopropyl-3-phenyl-5-(p-tolyloxy)-3H-1,2,3- triazolo[4,5-d]pyrimidin-7(6H)-one top

Crystal data top

C₂₀H₁₉N₅O₂	F(000) = 1520
M_r = 361.40	D_x = 1.282 Mg m⁻³
Orthorhombic, C222₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2c 2	Cell parameters from 7338 reflections
a = 10.2335 (6) Å	θ = 2.2–22.6°
b = 21.8532 (12) Å	µ = 0.09 mm⁻¹
c = 16.7441 (9) Å	T = 298 K
V = 3744.6 (4) Å³	Block, colorless
Z = 8	0.20 × 0.20 × 0.20 mm

Data collection top

Bruker SMART CCD diffractometer	1790 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.023
Graphite monochromator	θ_max = 27.0°, θ_min = 2.2°
φ and ω scans	h = −13→13
21260 measured reflections	k = −27→27
2285 independent reflections	l = −21→21

Refinement top

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)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.144	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.1088P)² + 0.0578P] where P = (F_o² + 2F_c²)/3
2285 reflections	(Δ/σ)_max < 0.001
446 parameters	Δρ_max = 0.17 e Å⁻³
15 restraints	Δρ_min = −0.17 e Å⁻³

Crystal data top

C₂₀H₁₉N₅O₂	V = 3744.6 (4) Å³
M_r = 361.40	Z = 8
Orthorhombic, C222₁	Mo Kα radiation
a = 10.2335 (6) Å	µ = 0.09 mm⁻¹
b = 21.8532 (12) Å	T = 298 K
c = 16.7441 (9) Å	0.20 × 0.20 × 0.20 mm

Data collection top

Bruker SMART CCD diffractometer	1790 reflections with I > 2σ(I)
21260 measured reflections	R_int = 0.023
2285 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.050	15 restraints
wR(F²) = 0.144	H-atom parameters constrained
S = 1.06	Δρ_max = 0.17 e Å⁻³
2285 reflections	Δρ_min = −0.17 e Å⁻³
446 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-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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.5967 (13)	0.0694 (5)	0.1729 (8)	0.111 (2)	0.57 (2)
O2	0.3920 (17)	0.2076 (8)	0.0153 (9)	0.096 (3)	0.57 (2)
N1	0.6946 (14)	0.2696 (5)	0.2174 (10)	0.069 (2)	0.57 (2)
N2	0.7566 (13)	0.2328 (6)	0.2727 (7)	0.082 (2)	0.57 (2)
N3	0.7249 (10)	0.1753 (5)	0.2602 (6)	0.082 (3)	0.57 (2)
N4	0.5505 (14)	0.2489 (7)	0.1072 (8)	0.103 (5)	0.57 (2)
N5	0.500 (2)	0.1435 (10)	0.0927 (11)	0.085 (3)	0.57 (2)
C1	0.7134 (7)	0.3323 (3)	0.2161 (3)	0.0691 (17)	0.57 (2)
C2	0.6409 (8)	0.3694 (3)	0.1653 (6)	0.105 (3)	0.57 (2)
H2	0.5805	0.3521	0.1305	0.126*	0.57 (2)
C3	0.6587 (8)	0.4325 (3)	0.1665 (7)	0.117 (3)	0.57 (2)
H3	0.6102	0.4573	0.1325	0.141*	0.57 (2)
C4	0.7490 (7)	0.4584 (4)	0.2184 (5)	0.113 (3)	0.57 (2)
H4	0.7609	0.5006	0.2192	0.135*	0.57 (2)
C5	0.8215 (8)	0.4213 (5)	0.2692 (3)	0.110 (3)	0.57 (2)
H5	0.8819	0.4386	0.3040	0.132*	0.57 (2)
C6	0.8037 (8)	0.3582 (5)	0.2681 (3)	0.102 (3)	0.57 (2)
H6	0.8522	0.3334	0.3021	0.123*	0.57 (2)
C7	0.6443 (19)	0.1776 (9)	0.1971 (12)	0.081 (3)	0.57 (2)
C8	0.6235 (13)	0.2323 (6)	0.1690 (7)	0.062 (2)	0.57 (2)
C9	0.489 (3)	0.2026 (13)	0.0766 (15)	0.090 (5)	0.57 (2)
C10	0.586 (2)	0.1249 (10)	0.1598 (12)	0.085 (4)	0.57 (2)
C11	0.3987 (9)	0.2670 (3)	−0.0196 (6)	0.104 (4)	0.57 (2)
C12	0.3310 (9)	0.3155 (4)	0.0145 (5)	0.082 (3)	0.57 (2)
H12	0.2821	0.3095	0.0606	0.099*	0.57 (2)
C13	0.3364 (9)	0.3732 (3)	−0.0204 (6)	0.090 (2)	0.57 (2)
H13	0.2911	0.4057	0.0023	0.108*	0.57 (2)
C14	0.4095 (8)	0.3823 (4)	−0.0894 (6)	0.084 (2)	0.57 (2)
C15	0.4772 (9)	0.3337 (6)	−0.1235 (5)	0.097 (3)	0.57 (2)
H15	0.5261	0.3398	−0.1696	0.116*	0.57 (2)
C16	0.4718 (10)	0.2760 (5)	−0.0886 (6)	0.095 (2)	0.57 (2)
H16	0.5171	0.2435	−0.1113	0.114*	0.57 (2)
C17	0.4124 (14)	0.4466 (7)	−0.1241 (10)	0.136 (4)	0.57 (2)
H17A	0.3397	0.4696	−0.1038	0.204*	0.57 (2)
H17B	0.4069	0.4445	−0.1812	0.204*	0.57 (2)
H17C	0.4925	0.4664	−0.1090	0.204*	0.57 (2)
C18	0.4324 (15)	0.0923 (7)	0.0447 (9)	0.095 (3)	0.57 (2)
H18	0.4657	0.0539	0.0670	0.114*	0.57 (2)
C19	0.2897 (15)	0.0907 (8)	0.0583 (10)	0.125 (5)	0.57 (2)
H19A	0.2496	0.1250	0.0320	0.188*	0.57 (2)
H19B	0.2723	0.0928	0.1145	0.188*	0.57 (2)
H19C	0.2545	0.0534	0.0371	0.188*	0.57 (2)
C20	0.4717 (15)	0.0914 (10)	−0.0428 (10)	0.112 (3)	0.57 (2)
H20A	0.4440	0.0536	−0.0666	0.167*	0.57 (2)
H20B	0.5650	0.0950	−0.0470	0.167*	0.57 (2)
H20C	0.4311	0.1251	−0.0700	0.167*	0.57 (2)
C1A	0.7079 (12)	0.3091 (7)	0.2237 (6)	0.094 (3)	0.43 (2)
C2A	0.6177 (10)	0.3523 (7)	0.1975 (9)	0.111 (4)	0.43 (2)
H2A	0.5398	0.3396	0.1742	0.134*	0.43 (2)
C3A	0.6440 (10)	0.4143 (7)	0.2062 (12)	0.142 (5)	0.43 (2)
H3A	0.5837	0.4432	0.1887	0.170*	0.43 (2)
C4A	0.7605 (13)	0.4332 (8)	0.2410 (9)	0.134 (5)	0.43 (2)
H4A	0.7781	0.4748	0.2468	0.161*	0.43 (2)
C5A	0.8507 (13)	0.3901 (10)	0.2672 (6)	0.140 (6)	0.43 (2)
H5A	0.9286	0.4028	0.2905	0.168*	0.43 (2)
C6A	0.8244 (12)	0.3281 (10)	0.2585 (7)	0.136 (5)	0.43 (2)
H6A	0.8848	0.2992	0.2761	0.163*	0.43 (2)
C7A	0.6291 (16)	0.1569 (9)	0.1872 (9)	0.060 (3)	0.43 (2)
C8A	0.610 (2)	0.2128 (9)	0.1634 (11)	0.070 (4)	0.43 (2)
C9A	0.480 (3)	0.1980 (13)	0.0641 (17)	0.067 (4)	0.43 (2)
C10A	0.559 (3)	0.1085 (15)	0.1430 (15)	0.081 (4)	0.43 (2)
C11A	0.4049 (8)	0.2736 (4)	−0.0202 (5)	0.056 (2)	0.43 (2)
C12A	0.3332 (13)	0.3137 (5)	0.0270 (7)	0.102 (5)	0.43 (2)
H12A	0.2928	0.2996	0.0732	0.122*	0.43 (2)
C13A	0.3218 (16)	0.3748 (5)	0.0050 (10)	0.122 (5)	0.43 (2)
H13A	0.2738	0.4016	0.0366	0.147*	0.43 (2)
C14A	0.3822 (16)	0.3958 (4)	−0.0641 (10)	0.094 (4)	0.43 (2)
C15A	0.4539 (15)	0.3557 (7)	−0.1113 (6)	0.089 (4)	0.43 (2)
H15A	0.4943	0.3698	−0.1576	0.107*	0.43 (2)
C16A	0.4653 (11)	0.2946 (6)	−0.0894 (5)	0.093 (3)	0.43 (2)
H16A	0.5133	0.2678	−0.1210	0.111*	0.43 (2)
C17A	0.377 (2)	0.4628 (10)	−0.0866 (14)	0.147 (6)	0.43 (2)
H17D	0.3001	0.4811	−0.0642	0.221*	0.43 (2)
H17E	0.3749	0.4667	−0.1437	0.221*	0.43 (2)
H17F	0.4532	0.4832	−0.0662	0.221*	0.43 (2)
C18A	0.3959 (18)	0.0886 (12)	0.0309 (13)	0.106 (5)	0.43 (2)
H18A	0.4062	0.0485	0.0563	0.127*	0.43 (2)
C19A	0.2578 (17)	0.1054 (11)	0.0417 (11)	0.107 (4)	0.43 (2)
H19D	0.2372	0.1396	0.0081	0.160*	0.43 (2)
H19E	0.2427	0.1162	0.0965	0.160*	0.43 (2)
H19F	0.2034	0.0713	0.0276	0.160*	0.43 (2)
C20A	0.441 (3)	0.0808 (14)	−0.0529 (15)	0.134 (8)	0.43 (2)
H20D	0.3923	0.0485	−0.0778	0.200*	0.43 (2)
H20E	0.5323	0.0708	−0.0532	0.200*	0.43 (2)
H20F	0.4274	0.1183	−0.0818	0.200*	0.43 (2)
O1A	0.5643 (15)	0.0529 (8)	0.1518 (9)	0.105 (3)	0.43 (2)
O2A	0.4187 (19)	0.2151 (8)	0.0014 (9)	0.076 (3)	0.43 (2)
N1A	0.686 (2)	0.2462 (10)	0.2155 (15)	0.080 (4)	0.43 (2)
N2A	0.7450 (14)	0.2046 (8)	0.2667 (8)	0.086 (5)	0.43 (2)
N3A	0.7055 (19)	0.1495 (10)	0.2479 (11)	0.094 (4)	0.43 (2)
N4A	0.5407 (11)	0.2413 (7)	0.1048 (5)	0.057 (2)	0.43 (2)
N5A	0.479 (2)	0.1328 (10)	0.0799 (11)	0.074 (4)	0.43 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.131 (6)	0.082 (4)	0.120 (6)	−0.009 (3)	−0.002 (4)	0.020 (4)
O2	0.090 (5)	0.086 (5)	0.111 (7)	−0.007 (3)	−0.014 (4)	0.009 (4)
N1	0.066 (3)	0.087 (7)	0.055 (2)	−0.002 (6)	−0.0045 (19)	0.004 (7)
N2	0.091 (3)	0.094 (6)	0.061 (2)	0.008 (5)	−0.014 (2)	0.006 (4)
N3	0.097 (7)	0.085 (10)	0.064 (5)	−0.003 (8)	−0.011 (4)	0.016 (8)
N4	0.111 (8)	0.096 (6)	0.103 (7)	0.004 (5)	−0.015 (5)	−0.008 (4)
N5	0.088 (5)	0.077 (5)	0.091 (6)	−0.010 (3)	0.001 (4)	−0.014 (4)
C1	0.063 (2)	0.092 (4)	0.052 (2)	0.000 (3)	0.000 (2)	−0.007 (2)
C2	0.103 (5)	0.108 (5)	0.104 (5)	0.001 (3)	−0.034 (4)	−0.005 (4)
C3	0.128 (5)	0.094 (4)	0.129 (7)	0.010 (4)	−0.028 (5)	−0.012 (4)
C4	0.140 (6)	0.096 (4)	0.102 (5)	0.003 (4)	−0.006 (4)	−0.028 (4)
C5	0.131 (6)	0.114 (6)	0.086 (4)	−0.008 (5)	−0.028 (4)	−0.027 (4)
C6	0.122 (6)	0.115 (7)	0.070 (3)	−0.014 (5)	−0.031 (3)	−0.003 (3)
C7	0.086 (5)	0.079 (10)	0.079 (5)	−0.004 (5)	0.003 (4)	0.002 (5)
C8	0.060 (3)	0.070 (5)	0.056 (4)	−0.002 (4)	0.002 (3)	0.000 (4)
C9	0.084 (6)	0.109 (11)	0.077 (9)	0.020 (7)	−0.009 (6)	0.007 (6)
C10	0.084 (9)	0.082 (12)	0.089 (12)	0.003 (6)	0.013 (7)	0.018 (7)
C11	0.093 (7)	0.119 (9)	0.101 (9)	−0.009 (6)	−0.017 (6)	−0.010 (7)
C12	0.075 (5)	0.095 (7)	0.077 (3)	0.002 (4)	−0.002 (3)	−0.001 (3)
C13	0.077 (4)	0.090 (5)	0.104 (6)	0.019 (3)	−0.004 (4)	0.001 (3)
C14	0.071 (4)	0.097 (5)	0.083 (5)	0.009 (4)	−0.003 (3)	0.004 (4)
C15	0.092 (4)	0.112 (7)	0.086 (4)	0.025 (5)	−0.002 (3)	0.009 (5)
C16	0.090 (4)	0.112 (5)	0.083 (4)	0.025 (4)	0.000 (3)	−0.004 (3)
C17	0.129 (7)	0.128 (8)	0.152 (10)	0.006 (5)	−0.005 (7)	0.040 (7)
C18	0.102 (6)	0.075 (4)	0.106 (6)	−0.008 (4)	0.005 (5)	−0.016 (4)
C19	0.121 (9)	0.114 (7)	0.140 (9)	−0.031 (7)	0.000 (7)	−0.016 (6)
C20	0.111 (6)	0.113 (6)	0.111 (6)	−0.006 (5)	0.015 (5)	−0.052 (4)
C1A	0.098 (6)	0.115 (10)	0.071 (5)	−0.016 (9)	0.006 (4)	0.007 (8)
C2A	0.110 (6)	0.112 (7)	0.113 (8)	0.008 (6)	0.001 (6)	−0.018 (6)
C3A	0.148 (10)	0.133 (9)	0.145 (12)	0.011 (8)	−0.008 (9)	−0.010 (9)
C4A	0.166 (14)	0.131 (10)	0.104 (9)	−0.021 (9)	0.015 (9)	−0.039 (10)
C5A	0.165 (14)	0.154 (16)	0.102 (7)	−0.014 (11)	−0.009 (7)	−0.015 (9)
C6A	0.156 (11)	0.162 (13)	0.090 (6)	−0.024 (9)	−0.019 (6)	−0.010 (8)
C7A	0.065 (6)	0.068 (12)	0.049 (5)	0.000 (6)	0.000 (4)	0.008 (6)
C8A	0.071 (5)	0.081 (10)	0.058 (4)	0.003 (7)	0.003 (4)	0.002 (7)
C9A	0.070 (8)	0.075 (7)	0.056 (6)	0.013 (5)	−0.001 (4)	−0.006 (4)
C10A	0.083 (10)	0.094 (16)	0.067 (7)	0.010 (8)	0.011 (6)	0.014 (7)
C11A	0.055 (4)	0.064 (4)	0.049 (4)	0.012 (3)	−0.021 (3)	−0.001 (3)
C12A	0.097 (10)	0.107 (11)	0.101 (7)	0.022 (8)	−0.004 (6)	0.015 (6)
C13A	0.109 (8)	0.137 (11)	0.121 (10)	0.013 (7)	−0.006 (7)	0.005 (7)
C14A	0.085 (8)	0.101 (7)	0.096 (10)	0.011 (5)	−0.016 (6)	0.000 (6)
C15A	0.090 (8)	0.103 (9)	0.074 (5)	0.005 (7)	−0.003 (4)	0.000 (6)
C16A	0.094 (6)	0.112 (8)	0.072 (6)	0.014 (5)	−0.018 (5)	−0.014 (5)
C17A	0.154 (14)	0.129 (11)	0.159 (15)	−0.003 (9)	−0.017 (11)	0.024 (10)
C18A	0.104 (11)	0.111 (10)	0.103 (8)	0.005 (8)	0.003 (7)	0.014 (7)
C19A	0.093 (7)	0.131 (11)	0.096 (7)	0.005 (6)	0.011 (6)	−0.011 (6)
C20A	0.150 (16)	0.133 (15)	0.118 (10)	0.004 (11)	−0.006 (10)	−0.020 (9)
O1A	0.121 (7)	0.090 (7)	0.106 (6)	0.010 (5)	−0.006 (5)	0.028 (5)
O2A	0.092 (8)	0.068 (4)	0.069 (4)	−0.005 (4)	−0.025 (5)	0.002 (4)
N1A	0.080 (6)	0.105 (12)	0.056 (4)	0.008 (8)	0.000 (4)	0.004 (9)
N2A	0.097 (8)	0.091 (15)	0.069 (6)	−0.003 (13)	−0.004 (5)	0.015 (13)
N3A	0.094 (6)	0.116 (11)	0.072 (5)	0.006 (8)	−0.005 (4)	0.016 (7)
N4A	0.048 (3)	0.076 (5)	0.046 (4)	0.006 (3)	−0.012 (3)	0.001 (3)
N5A	0.087 (8)	0.071 (9)	0.063 (5)	0.011 (6)	0.001 (5)	0.005 (5)

Geometric parameters (Å, º) top

O1—C10	1.24 (3)	C1A—C2A	1.3900
O2—C11	1.425 (17)	C1A—C6A	1.3900
O2—C9	1.43 (2)	C1A—N1A	1.401 (15)
N1—C8	1.360 (15)	C2A—C3A	1.3900
N1—N2	1.381 (19)	C2A—H2A	0.9300
N1—C1	1.383 (9)	C3A—C4A	1.3900
N2—N3	1.315 (9)	C3A—H3A	0.9300
N3—C7	1.34 (3)	C4A—C5A	1.3900
N4—C9	1.300 (13)	C4A—H4A	0.9300
N4—C8	1.328 (11)	C5A—C6A	1.3900
N5—C9	1.32 (3)	C5A—H5A	0.9300
N5—C10	1.48 (3)	C6A—H6A	0.9300
N5—C18	1.543 (11)	C7A—N3A	1.29 (3)
C1—C2	1.3900	C7A—C8A	1.30 (2)
C1—C6	1.3900	C7A—C10A	1.477 (16)
C2—C3	1.3900	C8A—N4A	1.358 (13)
C2—H2	0.9300	C8A—N1A	1.38 (2)
C3—C4	1.3900	C9A—O2A	1.28 (3)
C3—H3	0.9300	C9A—N4A	1.321 (12)
C4—C5	1.3900	C9A—N5A	1.45 (3)
C4—H4	0.9300	C10A—O1A	1.23 (4)
C5—C6	1.3900	C10A—N5A	1.44 (4)
C5—H5	0.9300	C11A—O2A	1.34 (2)
C6—H6	0.9300	C11A—C12A	1.3900
C7—C8	1.30 (2)	C11A—C16A	1.3900
C7—C10	1.440 (13)	C12A—C13A	1.3900
C11—C12	1.3900	C12A—H12A	0.9300
C11—C16	1.3900	C13A—C14A	1.3900
C12—C13	1.3900	C13A—H13A	0.9300
C12—H12	0.9300	C14A—C15A	1.3900
C13—C14	1.3900	C14A—C17A	1.51 (2)
C13—H13	0.9300	C15A—C16A	1.3900
C14—C15	1.3900	C15A—H15A	0.9300
C14—C17	1.522 (14)	C16A—H16A	0.9300
C15—C16	1.3900	C17A—H17D	0.9600
C15—H15	0.9300	C17A—H17E	0.9600
C16—H16	0.9300	C17A—H17F	0.9600
C17—H17A	0.9600	C18A—C19A	1.471 (14)
C17—H17B	0.9600	C18A—C20A	1.487 (14)
C17—H17C	0.9600	C18A—N5A	1.528 (15)
C18—C19	1.478 (12)	C18A—H18A	0.9800
C18—C20	1.519 (12)	C19A—H19D	0.9600
C18—H18	0.9800	C19A—H19E	0.9600
C19—H19A	0.9600	C19A—H19F	0.9600
C19—H19B	0.9600	C20A—H20D	0.9600
C19—H19C	0.9600	C20A—H20E	0.9600
C20—H20A	0.9600	C20A—H20F	0.9600
C20—H20B	0.9600	N1A—N2A	1.39 (3)
C20—H20C	0.9600	N2A—N3A	1.309 (14)

C11—O2—C9	109.3 (16)	C3A—C4A—C5A	120.0
C8—N1—N2	107.2 (9)	C3A—C4A—H4A	120.0
C8—N1—C1	131.2 (12)	C5A—C4A—H4A	120.0
N2—N1—C1	121.6 (11)	C6A—C5A—C4A	120.0
N3—N2—N1	109.6 (11)	C6A—C5A—H5A	120.0
N2—N3—C7	104.1 (12)	C4A—C5A—H5A	120.0
C9—N4—C8	111.6 (12)	C5A—C6A—C1A	120.0
C9—N5—C10	118.4 (13)	C5A—C6A—H6A	120.0
C9—N5—C18	124.0 (17)	C1A—C6A—H6A	120.0
C10—N5—C18	117.6 (17)	N3A—C7A—C8A	116.8 (15)
N1—C1—C2	120.9 (7)	N3A—C7A—C10A	126.7 (17)
N1—C1—C6	119.1 (7)	C8A—C7A—C10A	116.4 (18)
C2—C1—C6	120.0	C7A—C8A—N4A	136.9 (15)
C3—C2—C1	120.0	C7A—C8A—N1A	102.5 (14)
C3—C2—H2	120.0	N4A—C8A—N1A	120.6 (16)
C1—C2—H2	120.0	O2A—C9A—N4A	116 (2)
C4—C3—C2	120.0	O2A—C9A—N5A	115.8 (16)
C4—C3—H3	120.0	N4A—C9A—N5A	127.8 (19)
C2—C3—H3	120.0	O1A—C10A—N5A	118.8 (15)
C5—C4—C3	120.0	O1A—C10A—C7A	129 (2)
C5—C4—H4	120.0	N5A—C10A—C7A	112 (2)
C3—C4—H4	120.0	O2A—C11A—C12A	120.3 (9)
C4—C5—C6	120.0	O2A—C11A—C16A	119.7 (9)
C4—C5—H5	120.0	C12A—C11A—C16A	120.0
C6—C5—H5	120.0	C11A—C12A—C13A	120.0
C5—C6—C1	120.0	C11A—C12A—H12A	120.0
C5—C6—H6	120.0	C13A—C12A—H12A	120.0
C1—C6—H6	120.0	C14A—C13A—C12A	120.0
C8—C7—N3	114.7 (9)	C14A—C13A—H13A	120.0
C8—C7—C10	120.5 (16)	C12A—C13A—H13A	120.0
N3—C7—C10	124.7 (17)	C15A—C14A—C13A	120.0
C7—C8—N4	128.6 (12)	C15A—C14A—C17A	119.1 (10)
C7—C8—N1	104.4 (11)	C13A—C14A—C17A	120.8 (10)
N4—C8—N1	127.0 (13)	C14A—C15A—C16A	120.0
N4—C9—N5	129.5 (18)	C14A—C15A—H15A	120.0
N4—C9—O2	124 (2)	C16A—C15A—H15A	120.0
N5—C9—O2	106.5 (16)	C15A—C16A—C11A	120.0
O1—C10—C7	131.8 (17)	C15A—C16A—H16A	120.0
O1—C10—N5	117.2 (13)	C11A—C16A—H16A	120.0
C7—C10—N5	110.9 (16)	C14A—C17A—H17D	109.5
C12—C11—C16	120.0	C14A—C17A—H17E	109.5
C12—C11—O2	120.2 (8)	H17D—C17A—H17E	109.5
C16—C11—O2	119.8 (8)	C14A—C17A—H17F	109.5
C13—C12—C11	120.0	H17D—C17A—H17F	109.5
C13—C12—H12	120.0	H17E—C17A—H17F	109.5
C11—C12—H12	120.0	C19A—C18A—C20A	116.2 (14)
C12—C13—C14	120.0	C19A—C18A—N5A	108.2 (19)
C12—C13—H13	120.0	C20A—C18A—N5A	113.9 (17)
C14—C13—H13	120.0	C19A—C18A—H18A	105.9
C15—C14—C13	120.0	C20A—C18A—H18A	105.9
C15—C14—C17	122.7 (7)	N5A—C18A—H18A	105.9
C13—C14—C17	117.3 (7)	C18A—C19A—H19D	109.5
C14—C15—C16	120.0	C18A—C19A—H19E	109.5
C14—C15—H15	120.0	H19D—C19A—H19E	109.5
C16—C15—H15	120.0	C18A—C19A—H19F	109.5
C15—C16—C11	120.0	H19D—C19A—H19F	109.5
C15—C16—H16	120.0	H19E—C19A—H19F	109.5
C11—C16—H16	120.0	C18A—C20A—H20D	109.5
C19—C18—C20	114.2 (11)	C18A—C20A—H20E	109.5
C19—C18—N5	112.4 (12)	H20D—C20A—H20E	109.5
C20—C18—N5	113.1 (13)	C18A—C20A—H20F	109.5
C19—C18—H18	105.4	H20D—C20A—H20F	109.5
C20—C18—H18	105.4	H20E—C20A—H20F	109.5
N5—C18—H18	105.4	C9A—O2A—C11A	123.7 (16)
C2A—C1A—C6A	120.0	C8A—N1A—N2A	107.0 (11)
C2A—C1A—N1A	121.8 (13)	C8A—N1A—C1A	132 (2)
C6A—C1A—N1A	118.2 (13)	N2A—N1A—C1A	121 (2)
C3A—C2A—C1A	120.0	N3A—N2A—N1A	108.5 (17)
C3A—C2A—H2A	120.0	C7A—N3A—N2A	105.1 (19)
C1A—C2A—H2A	120.0	C9A—N4A—C8A	106.8 (13)
C2A—C3A—C4A	120.0	C10A—N5A—C9A	119.7 (16)
C2A—C3A—H3A	120.0	C10A—N5A—C18A	118.5 (17)
C4A—C3A—H3A	120.0	C9A—N5A—C18A	121.8 (18)

Experimental details

Crystal data
Chemical formula	C₂₀H₁₉N₅O₂
M_r	361.40
Crystal system, space group	Orthorhombic, C222₁
Temperature (K)	298
a, b, c (Å)	10.2335 (6), 21.8532 (12), 16.7441 (9)
V (Å³)	3744.6 (4)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.20 × 0.20 × 0.20

Data collection
Diffractometer	Bruker SMART CCD
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	21260, 2285, 1790
R_int	0.023
(sin θ/λ)_max (Å⁻¹)	0.639

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.050, 0.144, 1.06
No. of reflections	2285
No. of parameters	446
No. of restraints	15
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.17, −0.17

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009), SHELXTL97 (Sheldrick, 2008).

Acknowledgements

We gratefully acknowledge financial support of this work by the Educational Commission of Hubei Province of China (grant No. B200624004, B20092412), Shiyan Municipal Science and Technology Bureau (grant No. 20061835), and Yunyang Medical College (grant Nos. 2007QDJ15, 2007ZQB19, 2007ZQB20).

References

Bariana, D. S. (1971). J. Med. Chem. 14, 535–543. PubMed Web of Science Google Scholar
Bruker (2001). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Chen, X.-B. & Shi, D.-Q. (2006). Acta Cryst. E62, o4780–o4782. Web of Science CSD CrossRef IUCr Journals Google Scholar
Cox, P. J. & Wardell, J. L. (2003). Acta Cryst. C59, o706–o708. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Ding, M. W., Xu, S. Z. & Zhao, J. F. (2004). J. Org. Chem. 69, 8366–8371. Web of Science CrossRef PubMed CAS Google Scholar
Ferguson, G., Low, J. N., Nogueras, M., Cobo, J., Lopez, M. D., Quijano, M. L. & Sanchez, A. (1998). Acta Cryst. C54, IUC9800031. CrossRef IUCr Journals Google Scholar
Holland, A., Jackson, D., Chaplen, P., Lunt, E., Marshall, S., Pain, C. L. & Wooldridge, K. R. H. (1975). Eur. J. Med. Chem. 10, 447–449. CAS Google Scholar
Kirsop, P., Storey, J. M. D. & Harrison, W. T. A. (2006). Acta Cryst. C62, o376–o378. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Levine, R. J., Hall, T. C. & Harris, C. A. (1963). Cancer (N. Y.), 16, 269–272. CrossRef CAS Google Scholar
Maldonado, C. R., Quirós, M. & Salas, J. M. (2006). Acta Cryst. C62, o489–o491. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Mitchell, J. H., Skipper, H. E. & Bennett, L. L. (1950). Cancer Res. 10, 647–649. CAS Google Scholar
Montgomery, J. A., Schabel, F. M. & Skipper, H. E. (1962). Cancer Res. 22, 504–509. PubMed CAS Web of Science Google Scholar
Roblin, R. O., Lampen, J. O., English, J. P., Cole, Q. P. & Vaughan, J. R. (1945). J. Am. Chem. Soc. 67, 290–294. CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wang, H.-M., Chen, L.-L., Hu, T. & Zeng, X.-H. (2008). Acta Cryst. E64, o2404. Web of Science CSD CrossRef IUCr Journals Google Scholar
Wang, H.-M., Zeng, X.-H., Hu, Z.-Q., Li, G.-H. & Tian, J.-H. (2006). Acta Cryst. E62, o5038–o5040. Web of Science CSD CrossRef IUCr Journals Google Scholar
Xiao, L.-X. & Shi, D.-Q. (2007). Acta Cryst. E63, o2843. Web of Science CSD CrossRef IUCr Journals Google Scholar
Yamamoto, I., Inoki, R., Tamari, Y. & Iwatsubo, K. (1967). Jpn J. Pharmacol. 17, 140–142. CrossRef CAS PubMed Web of Science Google Scholar
Zeng, X.-H., Deng, S.-H., Qu, Y.-N. & Wang, H.-M. (2009). Acta Cryst. E65, o1142–o1143. Web of Science CSD CrossRef IUCr Journals Google Scholar
Zeng, X.-H., Ding, M.-W. & He, H.-W. (2006). Acta Cryst. E62, o731–o732. Web of Science CSD CrossRef IUCr Journals Google Scholar
Zeng, X. H., Liu, X. L., Deng, Sh. H., Chen P. & Wang, H. M. (2009). Acta Cryst. E65, o2583–o2584. Google Scholar
Zhao, J.-F., Hu, Y.-G., Ding, M.-W. & He, H.-W. (2005). Acta Cryst. E61, o2791–o2792. Web of Science CSD CrossRef IUCr Journals Google Scholar
Zhao, J. F., Wang, C. G. & Ding, M. W. (2005). Chin. J. Struct. Chem. 24, 439–444. Web of Science CrossRef CAS Google Scholar
Zhao, J. F., Xie, C., Ding, M. W. & He, H. W. (2005). Chem. Lett. 34, 1020–1022. Web of Science CrossRef Google Scholar

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