2-Chloro-8-methyl-3-[(pyrimidin-4-yl­oxy)meth­yl]quinoline

F Nawaz Khan; S Mohana Roopan; Venkatesha R Hathwar; Mehmet Akkurt

doi:10.1107/S1600536810011694

. 2010 Apr 2;66(Pt 5):o1010. doi: 10.1107/S1600536810011694

2-Chloro-8-methyl-3-[(pyrimidin-4-yloxy)methyl]quinoline

F Nawaz Khan ^a, S Mohana Roopan ^a, Venkatesha R Hathwar ^b, Mehmet Akkurt ^c,^*

PMCID: PMC2979073 PMID: 21579074

Abstract

In the title compound, C₁₅H₁₂ClN₃O, the quinoline ring system is essentially planar, with a maximum deviation of 0.017 (1) Å. The crystal packing is stabilized by π–π stacking interactions between the quinoline rings of adjacent molecule, with a centroid–centroid distance of 3.5913 (8) Å. A weak C—H⋯π contact is also observed between molecules.

Related literature

For pyrimidine analogues, see: Svenstrup et al. (2008 ▶). For quinoline analogues, see: Roopan & Khan (2009 ▶); Khan et al. (2009 ▶, 2010a ▶,b ▶). For the biological activity and mode of action of alkylating agent, see: Singer (1986 ▶). For the synthesis and regioselective alkylation of 4(3H)-pyrimidone, see: Roopan et al. (2010 ▶). For bond-length data, see: Allen et al. (1987 ▶). For a structural discussion on hydrogen bonding, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₅H₁₂ClN₃O
M _r = 285.73
Monoclinic,
a = 11.9975 (2) Å
b = 8.45037 (15) Å
c = 12.95869 (19) Å
β = 96.7619 (16)°
V = 1304.66 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.29 mm⁻¹
T = 295 K
0.23 × 0.18 × 0.15 mm

Data collection

Oxford Xcalibur Eos (Nova) CCD detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO RED; Oxford Diffraction, 2009 ▶) T _min = 0.936, T _max = 0.958
13753 measured reflections
2564 independent reflections
2005 reflections with I > 2σ(I)
R _int = 0.031

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.089
S = 1.07
2564 reflections
182 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CrysAlis PRO CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis PRO CCD; data reduction: CrysAlis PRO RED (Oxford Diffraction, 2009 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810011694/fj2289sup1.cif

e-66-o1010-sup1.cif^{(20.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810011694/fj2289Isup2.hkl

e-66-o1010-Isup2.hkl^{(123.4KB, hkl)}

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

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

Cg3 is the centroid of the C4–C9 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C10—H10A⋯Cg3ⁱ	0.97	2.72	3.5132 (15)	140

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank the FIST program for the data collection at SSCU, IISc, Bangalore and Professor T. N. Guru Row, IISc, Bangalore, for his help with the data collection. FNK thanks the DST for Fast Track Proposal funding.

supplementary crystallographic information

Comment

Alkylating agents have been studied extensively both for their biological effects and for their mode of action (Singer et al., 1986). There have been over the past 25 years a veritable deluge of reviews, often focusing on a single aspect or agent or adduct. Direct alkylation of oxygens in pyrimidine nucleosides, under physiological conditions, has been known only since the middle 1970s. The pyrimidine analogues (Svenstrup et al., 2008) such as naturally occurring azacamptothecin based molecule have been focused of great interest by reason of their diversified biological activities. Thus, modifications of biologically active azacamptothecin synthons may lead to achieve the highly expected effective drugs. In connection with the program of synthesis and regioselective alkylation of 4(3H)-pyrimidone (Roopan et al., 2010), we report herein the synthesis of 2-chloro-8-methyl-3-[(pyrimidin-4-yloxy)methyl]quinoline.

In the molecule of the title compound, Fig. 1, bond lengths and angles are in normal ranges (Allen et al., 1987). The quinoline ring system (N1/C1–C9) is essentially planar, with a maximum deviation of -0.017 (1) Å for atom C1. The quinoline system (N1/C1–C9) makes a dihedral angle of 4.99 (6)° with the piyrimidone ring (N2/N3/C11–C14).

In the title molecule, there is a weak intramolecular C—H···O interaction, generating an S(5) graph-set motif (Bernstein et al., 1995) (Table 1). The crystal packing is stabilized by π-π stacking interactions between the benzene rings of the quinoline ring system of the molecules related by the symmetry operator (1-x, 1-y, -z) [centroid-to-centroid distance = 3.5913 (8) Å]. In addition, a weak C—H···π contact is also observed between molecules (Table 1). The packing diagram viewing down the b-axis is shown in Fig. 2.

Experimental

To a mixed well solution of 4(3H)-pyrimidone (96 mg, 1 mmol, in 5 ml DMSO), NaH (25 mg, 1 mmol) and 2-chloro-3-(chloromethyl)-8-methylquinoline (225 mg, 1 mmol) were added and the resulting mixture was refluxed for 1 h. Completion of the reaction was monitored by TLC. After the completion of the reaction, cooled and removed the excess of solvent under reduced pressure. Crushed ice was mixed with the residue. White solid was formed, filtered and dried, purified by column chromatography using hexane and ethylacetate as the eluant. The low polar compound was subjected into crystallization by solvent evaporation from a solution of the compound in chloroform.