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Acta Crystallogr Sect E Struct Rep Online. 2010 March 1; 66(Pt 3): o650.
Published online 2010 February 17. doi:  10.1107/S1600536810004599
PMCID: PMC2983645

4-Chloro-2-{3-chloro-2-[(3,5-dimethyl­piperidin-1-yl)meth­yl]phenyl­sulfan­yl}-6-methoxy­pyrimidine

Abstract

In the title compound, C19H23Cl2N3OS, the dihedral angle between the benzene ring and the pyrimidine ring is 86.6 (9)°. The piperidine ring adopts a chair conformation.

Related literature

For the biological activity of pyrimidine derivatives, see: Joffe et al. (1989 [triangle]); Petersen & Schmidt (2003 [triangle]); Blum (2001 [triangle]); Gompper et al. (2004 [triangle]); Michael (2005 [triangle]); Nadal & Olavarria (2004 [triangle]).

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Object name is e-66-0o650-scheme1.jpg

Experimental

Crystal data

  • C19H23Cl2N3OS
  • M r = 412.36
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o650-efi1.jpg
  • a = 8.000 (4) Å
  • b = 11.454 (6) Å
  • c = 12.001 (7) Å
  • α = 87.820 (7)°
  • β = 76.084 (6)°
  • γ = 77.700 (6)°
  • V = 1042.9 (10) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.42 mm−1
  • T = 296 K
  • 0.39 × 0.37 × 0.25 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.852, T max = 0.901
  • 7861 measured reflections
  • 3848 independent reflections
  • 2553 reflections with I > 2σ(I)
  • R int = 0.019

Refinement

  • R[F 2 > 2σ(F 2)] = 0.041
  • wR(F 2) = 0.119
  • S = 1.03
  • 3848 reflections
  • 238 parameters
  • H-atom parameters constrained
  • Δρmax = 0.30 e Å−3
  • Δρmin = −0.31 e Å−3

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: SAINT (Bruker, 2004 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 [triangle]).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810004599/pb2021sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810004599/pb2021Isup2.hkl

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

Acknowledgments

This work was supported by the Doctoral Foundation of Luoyang Normal University.

supplementary crystallographic information

Comment

Pyrimidine derivatives are widespread in medicinal and natural products chemistry. A number of natural products, pharmaceuticals, and functional materials incorporate this heterocycle (Michael, 2005. Several examples of pharmaceutically important compounds include trimethoprim (Joffe et al., 1989), sulfadiazine (Petersen & Schmidt, 2003),Gleevec (imatinib mesilate) (Nadal & Olavarria, 2004), and Xeloda (capecitabine) (Blum, 2001). Natural and unnatural polymers also contain pyrimidine derivatives (Gompper et al., 2004). The potent physiological properties of these pyrimidine derivatives led to vast research of their use as medicines in the field of pharmaceutical chemistry. So in the recent decades, many chemists have been attracted by the synthesis of pyrimidines. In this context, we report the synthesis ofthe title compound.

The molecular structure is shown in Fig. 1. The bond lengths and angles are within normal ranges. The pyrimidine ring makes dihedral angles of 86.6 (9)° with the benzene ring. In the crystal structure,The cyclohexyl groups display chair-type conformation.

Experimental

To a solution of 2,4-dichloro-6-methoxypyrimidine (0.5 mmol) and 3-chloro-2-((3,5-dimethylpiperidin-1-yl)methyl)benzenethiol (0.5 mmol) in dry methylbenzene was added NaH (0.6 mmol). The mixture was stirred for 12 h at room temperature. After evaporation of the solvent, the residue was purified by column chromatography on silica gel to afford the title compound as a colorless solid (yield 78%). The title compound was recrystallized from CH2Cl2 at room temperature to give the desired crystals suitable for single-crystal X-ray diffraction.

Refinement

All H atoms were positioned geometrically and treated as riding, with C—H bond lengths constrained to 0.93 Å (aromatic CH) or 0.97 Å (methylene CH2), and with Uĩso~(H) = 1.2Ueq(C) or 1.5Ueq(methylene C).

Figures

Fig. 1.
View of the molecular structure of (I) with atom numbering scheme and 30% probability displacement ellipsoids.

Crystal data

C19H23Cl2N3OSZ = 2
Mr = 412.36F(000) = 432
Triclinic, P1Dx = 1.313 Mg m3
a = 8.000 (4) ÅMo Kα radiation, λ = 0.71073 Å
b = 11.454 (6) ÅCell parameters from 2557 reflections
c = 12.001 (7) Åθ = 2.5–25.9°
α = 87.820 (7)°µ = 0.42 mm1
β = 76.084 (6)°T = 296 K
γ = 77.700 (6)°Block, colourless
V = 1042.9 (10) Å30.39 × 0.37 × 0.25 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer3848 independent reflections
Radiation source: fine-focus sealed tube2553 reflections with I > 2σ(I)
graphiteRint = 0.019
phi and ω scansθmax = 25.5°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)h = −9→9
Tmin = 0.852, Tmax = 0.901k = −13→13
7861 measured reflectionsl = −14→14

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.041Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.119H-atom parameters constrained
S = 1.02w = 1/[σ2(Fo2) + (0.0498P)2 + 0.3748P] where P = (Fo2 + 2Fc2)/3
3848 reflections(Δ/σ)max < 0.001
238 parametersΔρmax = 0.30 e Å3
0 restraintsΔρmin = −0.30 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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)

xyzUiso*/Ueq
C10.8993 (3)0.4679 (2)0.3790 (2)0.0511 (6)
C20.7914 (4)0.5783 (3)0.4072 (2)0.0639 (7)
H20.80310.64170.35720.077*
C30.6657 (4)0.5951 (3)0.5096 (3)0.0772 (10)
H30.59130.66950.52810.093*
C40.6503 (4)0.5026 (4)0.5841 (3)0.0765 (10)
H40.56570.51360.65330.092*
C50.7618 (4)0.3926 (3)0.5555 (2)0.0649 (8)
C60.8897 (3)0.3706 (2)0.4527 (2)0.0517 (6)
C71.0146 (4)0.2522 (3)0.4215 (2)0.0613 (7)
H7A1.13420.26480.39770.074*
H7B1.00710.20190.48860.074*
C81.1282 (4)0.1048 (3)0.2685 (3)0.0722 (8)
H8A1.16010.04190.32060.087*
H8B1.22690.14390.24320.087*
C91.0929 (4)0.0498 (3)0.1644 (3)0.0773 (9)
H91.06120.11450.11260.093*
C100.9343 (4)−0.0090 (3)0.2069 (3)0.0838 (10)
H10A0.9048−0.04030.14180.101*
H10B0.9647−0.07530.25620.101*
C110.7761 (4)0.0801 (3)0.2730 (3)0.0867 (10)
H110.74380.14360.22020.104*
C120.8245 (4)0.1367 (3)0.3699 (3)0.0757 (9)
H12A0.72470.19720.40830.091*
H12B0.85030.07610.42560.091*
C131.2537 (5)−0.0357 (3)0.1000 (3)0.1102 (13)
H13A1.34850.00550.07490.165*
H13B1.2284−0.06760.03450.165*
H13C1.2871−0.09980.14940.165*
C140.6166 (5)0.0238 (4)0.3187 (5)0.151 (2)
H14A0.6428−0.03600.37380.226*
H14B0.5894−0.01240.25620.226*
H14C0.51740.08440.35470.226*
C150.9754 (3)0.4023 (2)0.14901 (19)0.0466 (6)
C161.0372 (3)0.3253 (2)−0.0292 (2)0.0483 (6)
C170.8596 (3)0.3280 (2)−0.0188 (2)0.0528 (6)
H170.81790.3030−0.07780.063*
C180.7513 (3)0.3697 (2)0.0833 (2)0.0500 (6)
C191.3329 (4)0.2760 (3)−0.1362 (3)0.0729 (8)
H19A1.35250.3554−0.13170.109*
H19B1.39980.2398−0.20850.109*
H19C1.36950.2292−0.07490.109*
Cl10.73889 (14)0.27940 (11)0.65587 (8)0.1117 (4)
Cl20.52759 (9)0.37327 (8)0.10766 (6)0.0780 (3)
N10.9758 (3)0.19101 (19)0.32894 (19)0.0585 (6)
N20.8031 (3)0.40866 (18)0.16994 (16)0.0497 (5)
N31.0978 (3)0.36245 (17)0.05379 (16)0.0480 (5)
O11.1505 (2)0.28158 (17)−0.12653 (14)0.0651 (5)
S11.06955 (9)0.45367 (7)0.25092 (6)0.0613 (2)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0428 (14)0.0719 (18)0.0443 (13)−0.0167 (13)−0.0152 (11)−0.0130 (13)
C20.0580 (18)0.0735 (19)0.0658 (18)−0.0100 (15)−0.0263 (15)−0.0174 (15)
C30.0500 (18)0.095 (2)0.088 (2)−0.0002 (16)−0.0258 (17)−0.043 (2)
C40.0440 (17)0.127 (3)0.0581 (18)−0.0211 (19)−0.0025 (13)−0.0381 (19)
C50.0497 (16)0.102 (2)0.0489 (15)−0.0256 (16)−0.0123 (12)−0.0129 (15)
C60.0387 (14)0.0765 (18)0.0458 (14)−0.0172 (13)−0.0144 (11)−0.0118 (13)
C70.0502 (16)0.0762 (19)0.0630 (17)−0.0127 (14)−0.0235 (13)−0.0044 (14)
C80.0544 (18)0.075 (2)0.086 (2)−0.0077 (15)−0.0158 (15)−0.0109 (16)
C90.088 (2)0.0613 (19)0.084 (2)−0.0076 (17)−0.0285 (18)−0.0092 (16)
C100.090 (2)0.063 (2)0.104 (3)−0.0093 (18)−0.038 (2)−0.0161 (18)
C110.069 (2)0.078 (2)0.126 (3)−0.0152 (17)−0.044 (2)−0.019 (2)
C120.0523 (18)0.080 (2)0.096 (2)−0.0149 (15)−0.0165 (16)−0.0183 (17)
C130.120 (3)0.099 (3)0.097 (3)−0.015 (2)−0.003 (2)−0.023 (2)
C140.081 (3)0.149 (4)0.234 (6)−0.048 (3)−0.028 (3)−0.070 (4)
C150.0469 (15)0.0525 (15)0.0424 (13)−0.0118 (12)−0.0128 (11)−0.0016 (11)
C160.0533 (16)0.0477 (14)0.0413 (13)−0.0097 (11)−0.0065 (11)−0.0045 (11)
C170.0575 (16)0.0600 (16)0.0461 (14)−0.0163 (13)−0.0179 (12)−0.0061 (12)
C180.0462 (15)0.0567 (15)0.0498 (14)−0.0110 (12)−0.0159 (12)−0.0012 (12)
C190.0481 (17)0.087 (2)0.0704 (19)−0.0035 (15)0.0056 (14)−0.0227 (16)
Cl10.1161 (8)0.1555 (10)0.0669 (5)−0.0582 (7)−0.0048 (5)0.0201 (6)
Cl20.0450 (4)0.1197 (7)0.0740 (5)−0.0198 (4)−0.0189 (3)−0.0135 (4)
N10.0447 (13)0.0622 (14)0.0712 (14)−0.0079 (11)−0.0197 (11)−0.0128 (11)
N20.0428 (12)0.0640 (13)0.0436 (11)−0.0108 (10)−0.0120 (9)−0.0063 (9)
N30.0459 (12)0.0536 (12)0.0436 (11)−0.0111 (9)−0.0076 (9)−0.0041 (9)
O10.0607 (12)0.0770 (13)0.0517 (11)−0.0109 (10)−0.0021 (9)−0.0198 (9)
S10.0499 (4)0.0947 (6)0.0468 (4)−0.0301 (4)−0.0108 (3)−0.0118 (3)

Geometric parameters (Å, °)

C1—C21.374 (4)C11—C141.527 (5)
C1—C61.400 (4)C11—H110.9800
C1—S11.778 (3)C12—N11.451 (3)
C2—C31.378 (4)C12—H12A0.9700
C2—H20.9300C12—H12B0.9700
C3—C41.367 (5)C13—H13A0.9600
C3—H30.9300C13—H13B0.9600
C4—C51.381 (4)C13—H13C0.9600
C4—H40.9300C14—H14A0.9600
C5—C61.392 (4)C14—H14B0.9600
C5—Cl11.744 (3)C14—H14C0.9600
C6—C71.504 (4)C15—N21.327 (3)
C7—N11.462 (3)C15—N31.336 (3)
C7—H7A0.9700C15—S11.759 (2)
C7—H7B0.9700C16—N31.327 (3)
C8—N11.450 (3)C16—O11.334 (3)
C8—C91.531 (4)C16—C171.390 (3)
C8—H8A0.9700C17—C181.356 (3)
C8—H8B0.9700C17—H170.9300
C9—C131.501 (5)C18—N21.331 (3)
C9—C101.533 (4)C18—Cl21.735 (3)
C9—H90.9800C19—O11.423 (3)
C10—C111.517 (4)C19—H19A0.9600
C10—H10A0.9700C19—H19B0.9600
C10—H10B0.9700C19—H19C0.9600
C11—C121.518 (4)
C2—C1—C6122.1 (2)C10—C11—H11107.8
C2—C1—S1118.1 (2)C14—C11—H11107.8
C6—C1—S1119.5 (2)N1—C12—C11112.1 (3)
C1—C2—C3120.0 (3)N1—C12—H12A109.2
C1—C2—H2120.0C11—C12—H12A109.2
C3—C2—H2120.0N1—C12—H12B109.2
C4—C3—C2120.1 (3)C11—C12—H12B109.2
C4—C3—H3119.9H12A—C12—H12B107.9
C2—C3—H3119.9C9—C13—H13A109.5
C3—C4—C5119.2 (3)C9—C13—H13B109.5
C3—C4—H4120.4H13A—C13—H13B109.5
C5—C4—H4120.4C9—C13—H13C109.5
C4—C5—C6122.9 (3)H13A—C13—H13C109.5
C4—C5—Cl1116.9 (2)H13B—C13—H13C109.5
C6—C5—Cl1120.1 (2)C11—C14—H14A109.5
C5—C6—C1115.7 (3)C11—C14—H14B109.5
C5—C6—C7123.5 (3)H14A—C14—H14B109.5
C1—C6—C7120.8 (2)C11—C14—H14C109.5
N1—C7—C6112.1 (2)H14A—C14—H14C109.5
N1—C7—H7A109.2H14B—C14—H14C109.5
C6—C7—H7A109.2N2—C15—N3127.9 (2)
N1—C7—H7B109.2N2—C15—S1120.94 (18)
C6—C7—H7B109.2N3—C15—S1111.10 (18)
H7A—C7—H7B107.9N3—C16—O1119.2 (2)
N1—C8—C9111.9 (2)N3—C16—C17122.8 (2)
N1—C8—H8A109.2O1—C16—C17118.0 (2)
C9—C8—H8A109.2C18—C17—C16115.4 (2)
N1—C8—H8B109.2C18—C17—H17122.3
C9—C8—H8B109.2C16—C17—H17122.3
H8A—C8—H8B107.9N2—C18—C17124.9 (2)
C13—C9—C8111.4 (3)N2—C18—Cl2115.60 (19)
C13—C9—C10112.8 (3)C17—C18—Cl2119.48 (19)
C8—C9—C10107.9 (3)O1—C19—H19A109.5
C13—C9—H9108.2O1—C19—H19B109.5
C8—C9—H9108.2H19A—C19—H19B109.5
C10—C9—H9108.2O1—C19—H19C109.5
C11—C10—C9111.0 (3)H19A—C19—H19C109.5
C11—C10—H10A109.4H19B—C19—H19C109.5
C9—C10—H10A109.4C8—N1—C12111.5 (2)
C11—C10—H10B109.4C8—N1—C7111.9 (2)
C9—C10—H10B109.4C12—N1—C7111.8 (2)
H10A—C10—H10B108.0C15—N2—C18113.9 (2)
C12—C11—C10110.0 (3)C16—N3—C15115.1 (2)
C12—C11—C14110.9 (3)C16—O1—C19118.0 (2)
C10—C11—C14112.3 (3)C15—S1—C1103.40 (12)
C12—C11—H11107.8
C6—C1—C2—C3−1.7 (4)N3—C16—C17—C18−1.0 (4)
S1—C1—C2—C3−175.51 (19)O1—C16—C17—C18178.0 (2)
C1—C2—C3—C41.2 (4)C16—C17—C18—N21.2 (4)
C2—C3—C4—C50.0 (4)C16—C17—C18—Cl2−178.17 (19)
C3—C4—C5—C6−0.7 (4)C9—C8—N1—C1259.6 (3)
C3—C4—C5—Cl1178.5 (2)C9—C8—N1—C7−174.4 (2)
C4—C5—C6—C10.1 (4)C11—C12—N1—C8−57.7 (3)
Cl1—C5—C6—C1−178.95 (17)C11—C12—N1—C7176.2 (2)
C4—C5—C6—C7178.6 (2)C6—C7—N1—C8157.2 (2)
Cl1—C5—C6—C7−0.5 (3)C6—C7—N1—C12−76.9 (3)
C2—C1—C6—C51.0 (3)N3—C15—N2—C18−0.1 (4)
S1—C1—C6—C5174.74 (17)S1—C15—N2—C18178.03 (18)
C2—C1—C6—C7−177.5 (2)C17—C18—N2—C15−0.7 (4)
S1—C1—C6—C7−3.8 (3)Cl2—C18—N2—C15178.70 (18)
C5—C6—C7—N1109.8 (3)O1—C16—N3—C15−178.6 (2)
C1—C6—C7—N1−71.8 (3)C17—C16—N3—C150.4 (3)
N1—C8—C9—C13177.8 (3)N2—C15—N3—C160.2 (4)
N1—C8—C9—C10−57.8 (3)S1—C15—N3—C16−178.04 (17)
C13—C9—C10—C11179.1 (3)N3—C16—O1—C190.5 (3)
C8—C9—C10—C1155.6 (4)C17—C16—O1—C19−178.5 (2)
C9—C10—C11—C12−54.9 (4)N2—C15—S1—C115.0 (2)
C9—C10—C11—C14−178.9 (3)N3—C15—S1—C1−166.64 (18)
C10—C11—C12—N155.2 (4)C2—C1—S1—C15−95.9 (2)
C14—C11—C12—N1180.0 (3)C6—C1—S1—C1590.2 (2)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PB2021).

References

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  • Joffe, A. M., Farley, J. D., Linden, D. & Goldsand, G. (1989). Am. J. Med., 87, 332–338. [PubMed]
  • Michael, J. P. (2005). Nat. Prod. Rep., 22, 627–646. [PubMed]
  • Nadal, E. & Olavarria, E. (2004). Int. J. Clin. Pract., 58, 511–516. [PubMed]
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  • Sheldrick, G. M. (1996). SADABS University of Göttingen, Germany.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst D65, 148–155. [PMC free article] [PubMed]

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