2-Chloro-6-[(2,4-dimeth­oxy­benz­yl)amino]-9-isopropyl-9H-purine

Radka Novotná; Zdeněk Trávníček

doi:10.1107/S1600536813004121

. 2013 Feb 16;69(Pt 3):o390. doi: 10.1107/S1600536813004121

2-Chloro-6-[(2,4-dimethoxybenzyl)amino]-9-isopropyl-9H-purine

Radka Novotná ^a, Zdeněk Trávníček ^a,^*

PMCID: PMC3588409 PMID: 23476575

Abstract

In the title compound, C₁₇H₂₀ClN₅O₂, the benzene ring and the purine ring system make a dihedral angle of 78.56 (4)°. In the crystal, molecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers. C—H⋯O and C—H⋯Cl contacts further link the molecules, forming a three-dimensional network.

Related literature

For the synthesis, see: Oh et al. (1999 ▶). For related structures, see: Trávníček & Popa (2007a ▶,b ▶); Trávníček et al. (2010 ▶); Čajan & Trávníček (2011 ▶). For the cytotoxic activity of related compounds, see: Benson et al. (2005 ▶); Meijer et al. (1997 ▶); Štarha et al. (2010 ▶); Vrzal et al. (2010 ▶).

Experimental

Crystal data

C₁₇H₂₀ClN₅O₂
M _r = 361.83
Triclinic,
a = 7.8620 (2) Å
b = 9.20164 (18) Å
c = 13.3027 (3) Å
α = 82.4472 (18)°
β = 74.803 (2)°
γ = 66.012 (2)°
V = 848.16 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 100 K
0.40 × 0.35 × 0.30 mm

Data collection

Agilent Xcalibur Sapphire2 diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012 ▶) T _min = 0.908, T _max = 0.930
7228 measured reflections
2965 independent reflections
2704 reflections with I > 2σ(I)
R _int = 0.009

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.079
S = 1.10
2965 reflections
230 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2006 ▶) and DIAMOND (Brandenburg, 2011 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(18.2KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813004121/ng5316sup1.cif

e-69-0o390-sup1.cif^{(18.2KB, cif)}

Click here for additional data file.^{(145.5KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813004121/ng5316Isup2.hkl

e-69-0o390-Isup2.hkl^{(145.5KB, hkl)}

Click here for additional data file.^{(6.8KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813004121/ng5316Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6—H6⋯N7ⁱ	0.88	2.16	2.9465 (15)	148
C16—H16C⋯Cl1ⁱⁱ	0.98	2.78	3.4607 (15)	127
C19—H19A⋯O2ⁱⁱⁱ	0.98	2.57	3.4709 (17)	154

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported financially by Palacký University (PrF_2012_009). The authors wish to thank Dr Igor Popa for carrying out the NMR spectroscopy measurements and Mr Tomáš Šilha for performing the CHN elemental analyses.

supplementary crystallographic information

Comment

The title compound (I) is derived from 6-benzylaminopurine, which is along with its derivatives classified among plant growth hormones called cytokinins, which influence crucial biochemical processes, such as cell cycle and division, in plant tissues. Suitable substitutions on the 6-benzylaminopurine skeleton, particularly in the C2 and N9 positions, lead to the formation of compounds that can act as inhibitors of enzymes cyclin dependent kinases in various phases of the human cell cycle (Meijer et al., 1997). One representative of such derivatives, (R)-Roscovitine, i.e. 2-[(R)-(1-ethyl-2-hydroxyethylamino)]-6-(benzylamino)-9-isopropylpurine (Seliciclib or CYC202), has entered the IIb phase of clinical trials in patients with nonsmall cell lung cancer (Benson et al., 2005). Moreover, 6-benzylaminopurine derivatives have been successfully used as N-donor ligands in transition metal complexes exhibiting varied types of biological activity. Even the title compound (I) has been employed as a ligand in the preparation of highly anticancer active platinum(II) oxalato complexes whose in vitro cytotoxic activity against various human cancer cells exceeded the commercially applied drug cisplatin (Štarha et al., 2010; Vrzal et al., 2010).

The molecular structure of (I) consists of discrete molecules of a three-substituted adenine derivative, 2-chloro-6-[(2,4-dimethoxybenzyl)amino]-9-isopropylpurine (Fig. 1). It is basically derived from the 6-benzylaminopurine skeleton by substitutions of H atoms by the methoxy groups in the positions 2 and 4 on the benzene ring, by chlorine, and the isopropyl group in the position C2, and N9, of purine, respectively. The molecule contains two heterocyclic rings pyrimidine and imidazole, which are almost coplanar, since they form a dihedral angle of 2.02 (5)°. Additionally, there is also a benzene ring present in the structure of (I) which is similarly to the other two rings essentially planar. The maximum deviations from the least-square planes fitted through the non-hydrogen atoms for each of the rings are as follows: 0.0102 (14) Å for C4 in pyrimidine, 0.0025 (14) Å for C8 in imidazole and 0.007 (2) Å for C14 in benzene. The benzene and purine ring systems form a dihedral angle of 78.56 (4)°.

The crystal structure of (I) consists of the molecules of 2-chloro-6-[(2,4-dimethoxybenzyl)amino]-9-isopropylpurine organized into centrosymmetric dimers connected by N—H···N hydrogen bonds (Table 1, Fig. 2). Additionally, varied types of non-covalent contacts are present in the structure of (I), namely C—H···O [d(C19···O2ⁱⁱⁱ) = 3.471 (2) Å; d(C17···O1^iv) = 3.358 (2) Å; symmetry codes: (iii) x, y, 1 + z; (iv) 1 - x, 1 - y, -z], C—H···Cl [d(C16···Cl1ⁱⁱ) = 3.820 (2) Å; d(C20···Cl1^v) = 3.461 (2) Å; symmetry codes: (ii) 1 - x, 2 - y, -z; (v) 2 - x, 2 - y, 1 - z], C—H···N [d(C17···N1^vi) = 3.435 (2) Å], C—H···C [d(C17···C2^vi) = 3.603 (2) Å; symmetry code: (vi) 2 - x, 1 - y, -z] as well as C···Cl contacts [d(C8···Cl1^vii) = 3.3888 (11) Å; symmetry code: (vii) 1 - x, 2 - y, 1 - z] (Fig. 3 and 4), forming an extended three-dimensional network.

Experimental

Compound (I) was prepared, as a prospective ligand for syntheses of transition metal complexes, by the procedure described previously (Oh et al., 1999). The resulting product was recrystallized from hot ethanol and crystals suitable for X-ray analysis were formed after several days of slow evaporation at room temperature. The crystals were characterized by elemental analysis, NMR spectroscopy and single-crystal X-ray analysis. ¹H NMR (DMF-d₇, TMS, 298 K, p.p.m.): 8.28 (s, 1H, C8H), 8.23 (t, 6.8, N6H, 1H), 7.23 (d, 8.2, C15H, 1H), 6.62 (d, 2.4, C12H, 1H), 6.49 (dd, 8.2, 2.4, C14H, 1H), 4.76 (sep, 6.8, C18H, 1H), 4.72 (d, 5.9, C9H, 2H), 3.89 (s, C16H, 3H), 3.80 (s, C17H, 3H), 1.58 (d, 6.8, C19H, C20H, 6H). ¹³C NMR (DMF-d₇, TMS, 298 K, p.p.m.): δ 161.03 (C13), 158.99 (C11), 156.27 (C6), 154.01 (C2), 150.49 (C4), 139.96 (C8), 129.37 (C15), 120.32 (C10), 119.71 (C5), 104.90 (C14), 98.93 (C12), 55.88 (C16), 55.65 (C17), 47.90 (C18), 39.36 (C9), 22.42 (C19, C20). ¹⁵N NMR (DMF-d₇, relative to DMF, 298 K, p.p.m.): δ 241.1 (N7), 228.5 (N1), 224.1 (N3), 179.6 (N9), 91.8 (N6). Analysis calculated for C₁₇H₂₀ClN₅O₂: C, 56.4; H, 5.6; N, 19.4. Found: C, 56.4; H, 5.9; N, 19.0%. Elemental analysis (C, H, N) was performed on a Thermo Scientific Flash 2000 CHNO-S Analyzer. The ¹H, ¹³C and ¹⁵N NMR spectra of the DMF-d₇ solutions were obtained at 300 K on a Varian 400 spectrometer at 400.00 MHz, 100.58 MHz and 40.53 MHz respectively. ¹H and ¹³C spectra were calibrated using tetramethylsilane (TMS) as a reference. The ¹⁵N NMR spectrum was measured relative to the DMF signals.