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Acta Crystallogr Sect E Struct Rep Online. 2009 July 1; 65(Pt 7): o1457.
Published online 2009 June 6. doi:  10.1107/S1600536809020212
PMCID: PMC2969350

2-(4-Chloro­phen­yl)-5-(3,4-dimethoxy­pheneth­yl)-6,7-dihydro­pyrazolo[1,5-a]pyrazin-4(5H)-one

Abstract

In the title compound, C22H22ClN3O3, the dihedral angles between the planes of the benzene rings and the pyrazole ring are 16.05 (10) and 84.84 (10)°. The conformation of the six-membered heterocyclic ring is close to a screw-boat. The crystal packing is stabilized by weak inter­molecular C—H(...)O inter­actions and is also consolidated by C—H(...)π inter­actions.

Related literature

For the bioactivity of pyrazole derivatives, see: Farag et al. (2008 [triangle]); Pan et al. (2008 [triangle]); Szabó et al. (2008 [triangle]); Xie et al. (2008 [triangle]). For a related structure, see: Zhang et al. (2008 [triangle]).

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Object name is e-65-o1457-scheme1.jpg

Experimental

Crystal data

  • C22H22ClN3O3
  • M r = 411.88
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1457-efi1.jpg
  • a = 7.1709 (4) Å
  • b = 10.6982 (5) Å
  • c = 13.9169 (6) Å
  • α = 81.156 (3)°
  • β = 77.150 (2)°
  • γ = 72.278 (2)°
  • V = 987.25 (8) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.22 mm−1
  • T = 293 K
  • 0.40 × 0.20 × 0.10 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker 2005 [triangle]) T min = 0.916, T max = 0.978
  • 8654 measured reflections
  • 3999 independent reflections
  • 2969 reflections with I > 2σ(I)
  • R int = 0.021

Refinement

  • R[F 2 > 2σ(F 2)] = 0.041
  • wR(F 2) = 0.115
  • S = 1.03
  • 3999 reflections
  • 326 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.20 e Å−3
  • Δρmin = −0.30 e Å−3

Data collection: SMART (Bruker, 2005 [triangle]); cell refinement: SAINT (Bruker, 2005 [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: XP in SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809020212/pv2160sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809020212/pv2160Isup2.hkl

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

Acknowledgments

This study was supported by the Science and Technology Developmental Project of Shandong Province (2008 GG10002034).

supplementary crystallographic information

Comment

Many pyrazole derivatives are known to exhibit a wide range of biological properties (Farag et al., 2008; Szabó et al., 2008). As part of our continuing project on the study of the interactions occurring between small molecules and proteins (Pan et al., 2008; Xie et al., 2008; Zhang et al., 2008), we report here the crystal structure of the title compound.

The molecular structure of the title compound is illustrated in Fig. 1. In contrast to our previously reported structure of a related compound (Zhang et al., 2008), the conformation of the six-membered heterocyclic ring (N2/N3/C9—C12) in the title compound is close to a screw-boat, with atoms C11 and N3 out of the plane of the remaining four atoms by 0.681 (2) and 0.214 (2) Å, respectively. In the crystal structure, the dihedral angles of the phenyl rings (C1—C6) and (C15—C20) with the pyrazol ring (N1/N2/C7—C9) are 16.05 (10) and 84.84 (10)°, respectively. The crystal packing is stabilized by intermolecular C—H···O interactions and is further consolidated by C—H···π interactions (Table 1).

Experimental

A solution containing ethyl-3-(4-chlorophenyl)-1-(2-bromoethyl)-1H-pyrazole-5-carboxylate (146 mg, 0.4 mmol), 2-(3,4-dimethoxyphenyl)ethanamine (724 mg, 4.0 mmol) and potassium iodide (13 mg, 0.08 mmol) in acetonitrile (10 ml) was refluxed under nitrogen for 3 h. Then the mixture was cooled, filtered, and the solvent was removed under reduced pressure. The product was obtained in 57% yield by column chromatography on silica gel using ethyl acetate as eluent. Crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution of the solid dissolved in ethyl acetate at room temperature for 5 days.

Refinement

The H atoms were located in difference Fourier maps, their positional and isotropic vibrational parameters were refined freely except for the methyl H-atoms which were included in the refinements at geometrically idealized positions in riding mode with C–H = 0.96 Å and Uiso(H) = 1.5 Ueq(C).

Figures

Fig. 1.
The molecular structure of the title compound showing displacement ellipsoids drawn at 30% probability level.

Crystal data

C22H22ClN3O3Z = 2
Mr = 411.88F(000) = 432
Triclinic, P1Dx = 1.386 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.1709 (4) ÅCell parameters from 2906 reflections
b = 10.6982 (5) Åθ = 3.0–26.1°
c = 13.9169 (6) ŵ = 0.22 mm1
α = 81.156 (3)°T = 293 K
β = 77.150 (2)°Block, colorless
γ = 72.278 (2)°0.40 × 0.20 × 0.10 mm
V = 987.25 (8) Å3

Data collection

Bruker SMART CCD area-detector diffractometer3999 independent reflections
Radiation source: fine-focus sealed tube2969 reflections with I > 2σ(I)
graphiteRint = 0.021
[var phi] and ω scansθmax = 26.4°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker 2005)h = −7→8
Tmin = 0.916, Tmax = 0.978k = −13→13
8654 measured reflectionsl = −17→17

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) = 0.115H atoms treated by a mixture of independent and constrained refinement
S = 1.03w = 1/[σ2(Fo2) + (0.0564P)2 + 0.1941P] where P = (Fo2 + 2Fc2)/3
3999 reflections(Δ/σ)max < 0.001
326 parametersΔρmax = 0.20 e Å3
0 restraintsΔρmin = −0.30 e Å3

Special details

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)

xyzUiso*/Ueq
Cl0.20421 (8)0.95549 (6)0.40014 (4)0.06084 (19)
N1−0.4397 (2)0.70036 (14)0.26041 (11)0.0390 (4)
N2−0.5553 (2)0.69103 (14)0.19947 (10)0.0367 (4)
N3−0.7921 (2)0.70588 (15)0.06451 (11)0.0390 (4)
O1−0.7274 (2)0.89705 (14)−0.00841 (10)0.0575 (4)
O2−1.3542 (2)0.72159 (14)−0.37111 (10)0.0533 (4)
O3−0.9862 (2)0.58773 (15)−0.41075 (10)0.0544 (4)
C10.0314 (3)0.91488 (18)0.34943 (14)0.0406 (4)
C2−0.0785 (3)0.8341 (2)0.40461 (15)0.0450 (5)
H2−0.065 (3)0.8025 (19)0.4699 (15)0.048 (6)*
C3−0.2109 (3)0.79940 (19)0.36251 (14)0.0419 (4)
H3−0.289 (3)0.744 (2)0.3994 (15)0.057 (6)*
C4−0.2335 (3)0.84383 (17)0.26496 (12)0.0343 (4)
C5−0.1236 (3)0.92790 (18)0.21187 (14)0.0390 (4)
H5−0.135 (3)0.9556 (19)0.1468 (15)0.046 (5)*
C60.0084 (3)0.96339 (19)0.25367 (14)0.0411 (4)
H60.082 (3)1.019 (2)0.2150 (15)0.049 (6)*
C7−0.3707 (3)0.80384 (17)0.21908 (12)0.0345 (4)
C8−0.4449 (3)0.86047 (19)0.13250 (13)0.0367 (4)
H8−0.421 (3)0.933 (2)0.0897 (15)0.047 (6)*
C9−0.5643 (3)0.78601 (17)0.12271 (12)0.0344 (4)
C10−0.6987 (3)0.80106 (19)0.05288 (13)0.0386 (4)
C11−0.7288 (4)0.5823 (2)0.12678 (16)0.0499 (5)
H11B−0.842 (3)0.543 (2)0.1422 (16)0.058 (6)*
H11A−0.600 (4)0.519 (2)0.0875 (17)0.066 (7)*
C12−0.6833 (4)0.6042 (2)0.22192 (15)0.0462 (5)
H12B−0.611 (3)0.522 (2)0.2536 (15)0.053 (6)*
H12A−0.811 (4)0.647 (2)0.2650 (17)0.069 (7)*
C13−0.9414 (3)0.7191 (2)0.00409 (15)0.0424 (5)
H13B−1.051 (3)0.684 (2)0.0467 (15)0.052 (6)*
C14−0.8546 (3)0.6485 (3)−0.08922 (16)0.0488 (5)
H14B−0.807 (4)0.551 (3)−0.0693 (18)0.073 (7)*
H14A−0.736 (4)0.676 (2)−0.1225 (17)0.066 (7)*
C15−0.9982 (3)0.67175 (18)−0.16026 (13)0.0383 (4)
C16−1.1963 (3)0.7426 (2)−0.13969 (14)0.0416 (4)
H16−1.255 (3)0.777 (2)−0.0773 (16)0.056 (6)*
C17−1.3206 (3)0.7617 (2)−0.20844 (15)0.0429 (5)
H17−1.458 (3)0.814 (2)−0.1909 (14)0.047 (6)*
C18−1.2466 (3)0.70993 (17)−0.29847 (14)0.0392 (4)
C19−1.0451 (3)0.63712 (18)−0.32041 (13)0.0387 (4)
C20−0.9246 (3)0.61940 (19)−0.25182 (14)0.0399 (4)
H20−0.793 (4)0.570 (2)−0.2684 (15)0.056 (6)*
C21−1.5441 (3)0.8157 (2)−0.36227 (18)0.0613 (6)
H21A−1.60420.8145−0.41720.092*
H21B−1.52930.9018−0.36210.092*
H21C−1.62750.7944−0.30160.092*
C22−0.7782 (3)0.5470 (2)−0.45031 (16)0.0593 (6)
H22A−0.75780.5147−0.51360.089*
H22B−0.71240.4782−0.40600.089*
H22C−0.72430.6205−0.45790.089*
H13A−0.998 (3)0.813 (2)−0.0122 (14)0.048 (6)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl0.0547 (4)0.0822 (4)0.0621 (4)−0.0307 (3)−0.0219 (3)−0.0163 (3)
N10.0449 (9)0.0398 (8)0.0395 (8)−0.0162 (7)−0.0192 (7)0.0006 (7)
N20.0410 (9)0.0385 (8)0.0365 (8)−0.0167 (7)−0.0151 (7)0.0016 (6)
N30.0417 (9)0.0462 (9)0.0368 (8)−0.0195 (7)−0.0158 (7)−0.0003 (7)
O10.0699 (10)0.0651 (9)0.0521 (8)−0.0378 (8)−0.0347 (8)0.0235 (7)
O20.0527 (9)0.0580 (9)0.0527 (8)−0.0050 (7)−0.0288 (7)−0.0097 (7)
O30.0521 (9)0.0692 (10)0.0418 (8)−0.0064 (8)−0.0151 (7)−0.0174 (7)
C10.0382 (11)0.0423 (10)0.0462 (11)−0.0098 (9)−0.0149 (8)−0.0116 (8)
C20.0546 (13)0.0505 (11)0.0368 (10)−0.0187 (10)−0.0192 (9)−0.0009 (9)
C30.0489 (12)0.0426 (11)0.0398 (10)−0.0193 (10)−0.0133 (9)0.0003 (8)
C40.0354 (10)0.0353 (9)0.0345 (9)−0.0091 (8)−0.0114 (8)−0.0043 (7)
C50.0416 (11)0.0415 (10)0.0356 (10)−0.0121 (9)−0.0123 (8)−0.0002 (8)
C60.0412 (11)0.0422 (11)0.0442 (11)−0.0172 (9)−0.0086 (9)−0.0045 (8)
C70.0352 (10)0.0355 (9)0.0344 (9)−0.0103 (8)−0.0088 (8)−0.0040 (7)
C80.0384 (10)0.0402 (10)0.0357 (9)−0.0168 (9)−0.0116 (8)0.0021 (8)
C90.0353 (10)0.0379 (9)0.0319 (9)−0.0126 (8)−0.0093 (7)0.0001 (7)
C100.0391 (11)0.0468 (11)0.0344 (10)−0.0174 (9)−0.0104 (8)−0.0007 (8)
C110.0605 (15)0.0477 (12)0.0535 (12)−0.0270 (12)−0.0243 (11)0.0039 (10)
C120.0566 (14)0.0456 (12)0.0471 (12)−0.0281 (11)−0.0209 (11)0.0083 (10)
C130.0391 (11)0.0545 (13)0.0415 (11)−0.0187 (10)−0.0145 (9)−0.0061 (9)
C140.0400 (12)0.0676 (15)0.0436 (11)−0.0146 (11)−0.0127 (9)−0.0133 (10)
C150.0396 (11)0.0434 (10)0.0385 (10)−0.0179 (9)−0.0109 (8)−0.0055 (8)
C160.0408 (11)0.0498 (11)0.0392 (10)−0.0164 (9)−0.0083 (9)−0.0109 (9)
C170.0360 (11)0.0456 (11)0.0495 (11)−0.0111 (9)−0.0101 (9)−0.0089 (9)
C180.0442 (11)0.0368 (10)0.0434 (10)−0.0155 (9)−0.0189 (9)0.0003 (8)
C190.0448 (11)0.0401 (10)0.0346 (9)−0.0140 (9)−0.0116 (8)−0.0029 (8)
C200.0374 (11)0.0433 (11)0.0407 (10)−0.0108 (9)−0.0102 (9)−0.0060 (8)
C210.0494 (13)0.0657 (15)0.0729 (15)−0.0083 (12)−0.0315 (12)−0.0051 (12)
C220.0617 (16)0.0631 (14)0.0478 (12)−0.0061 (12)−0.0090 (11)−0.0142 (10)

Geometric parameters (Å, °)

Cl—C11.7416 (18)C9—C101.474 (2)
N1—N21.3439 (19)C11—C121.499 (3)
N1—C71.346 (2)C11—H11B0.99 (2)
N2—C91.355 (2)C11—H11A1.06 (2)
N2—C121.452 (2)C12—H12B0.97 (2)
N3—C101.352 (2)C12—H12A1.00 (3)
N3—C131.465 (2)C13—C141.516 (3)
N3—C111.470 (2)C13—H13B1.01 (2)
O1—C101.227 (2)C13—H13A0.97 (2)
O2—C181.372 (2)C14—C151.523 (2)
O2—C211.418 (3)C14—H14B1.01 (3)
O3—C191.368 (2)C14—H14A0.98 (2)
O3—C221.425 (3)C15—C161.380 (3)
C1—C21.378 (3)C15—C201.399 (3)
C1—C61.380 (3)C16—C171.401 (3)
C2—C31.383 (3)C16—H160.95 (2)
C2—H20.94 (2)C17—C181.377 (3)
C3—C41.396 (2)C17—H170.97 (2)
C3—H30.95 (2)C18—C191.407 (3)
C4—C51.394 (3)C19—C201.380 (2)
C4—C71.476 (2)C20—H200.93 (2)
C5—C61.382 (3)C21—H21A0.9600
C5—H50.92 (2)C21—H21B0.9600
C6—H60.95 (2)C21—H21C0.9600
C7—C81.402 (2)C22—H22A0.9600
C8—C91.374 (2)C22—H22B0.9600
C8—H80.94 (2)C22—H22C0.9600
N2—N1—C7104.41 (13)C11—C12—H12B110.9 (12)
N1—N2—C9112.51 (14)N2—C12—H12A109.6 (14)
N1—N2—C12123.74 (14)C11—C12—H12A108.3 (13)
C9—N2—C12122.94 (15)H12B—C12—H12A112.2 (19)
C10—N3—C13119.09 (15)N3—C13—C14112.60 (17)
C10—N3—C11121.19 (15)N3—C13—H13B107.6 (12)
C13—N3—C11119.25 (15)C14—C13—H13B111.3 (12)
C18—O2—C21117.38 (16)N3—C13—H13A107.0 (12)
C19—O3—C22118.05 (15)C14—C13—H13A110.7 (12)
C2—C1—C6120.98 (17)H13B—C13—H13A107.4 (17)
C2—C1—Cl119.85 (14)C13—C14—C15114.67 (18)
C6—C1—Cl119.16 (15)C13—C14—H14B108.3 (14)
C1—C2—C3119.31 (18)C15—C14—H14B109.1 (14)
C1—C2—H2121.1 (13)C13—C14—H14A108.0 (14)
C3—C2—H2119.6 (13)C15—C14—H14A110.3 (13)
C2—C3—C4121.06 (19)H14B—C14—H14A106 (2)
C2—C3—H3120.8 (13)C16—C15—C20118.18 (17)
C4—C3—H3118.2 (13)C16—C15—C14123.66 (17)
C5—C4—C3118.22 (16)C20—C15—C14118.15 (17)
C5—C4—C7120.68 (15)C15—C16—C17121.03 (18)
C3—C4—C7121.10 (16)C15—C16—H16121.5 (13)
C6—C5—C4120.96 (17)C17—C16—H16117.4 (13)
C6—C5—H5120.4 (12)C18—C17—C16120.32 (19)
C4—C5—H5118.6 (12)C18—C17—H17122.1 (12)
C1—C6—C5119.42 (18)C16—C17—H17117.5 (12)
C1—C6—H6121.9 (12)O2—C18—C17125.43 (18)
C5—C6—H6118.7 (12)O2—C18—C19115.24 (16)
N1—C7—C8111.40 (15)C17—C18—C19119.32 (17)
N1—C7—C4120.36 (15)O3—C19—C20125.34 (18)
C8—C7—C4128.23 (16)O3—C19—C18115.07 (15)
C9—C8—C7104.71 (16)C20—C19—C18119.59 (17)
C9—C8—H8126.3 (12)C19—C20—C15121.57 (19)
C7—C8—H8129.0 (12)C19—C20—H20117.2 (13)
N2—C9—C8106.96 (15)C15—C20—H20121.2 (13)
N2—C9—C10120.98 (15)O2—C21—H21A109.5
C8—C9—C10131.84 (16)O2—C21—H21B109.5
O1—C10—N3123.38 (16)H21A—C21—H21B109.5
O1—C10—C9121.11 (16)O2—C21—H21C109.5
N3—C10—C9115.44 (15)H21A—C21—H21C109.5
N3—C11—C12112.58 (17)H21B—C21—H21C109.5
N3—C11—H11B106.1 (12)O3—C22—H22A109.5
C12—C11—H11B108.8 (12)O3—C22—H22B109.5
N3—C11—H11A109.6 (12)H22A—C22—H22B109.5
C12—C11—H11A108.6 (12)O3—C22—H22C109.5
H11B—C11—H11A111.2 (18)H22A—C22—H22C109.5
N2—C12—C11108.36 (16)H22B—C22—H22C109.5
N2—C12—H12B107.4 (13)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C5—H5···O1i0.92 (2)2.48 (2)3.341 (2)156.3 (17)
C8—H8···O1i0.94 (2)2.39 (2)3.296 (2)161.4 (19)
C11—H11B···Cg1ii0.99 (2)2.67 (2)3.413 (2)132.2 (16)
C12—H12A···Cg2iii1.00 (3)2.77 (2)3.640 (2)146.2 (17)
C21—H21B···Cg2iv0.962.983.531 (2)117

Symmetry codes: (i) −x−1, −y+2, −z; (ii) −x−2, −y+1, −z; (iii) x−1, y, z; (iv) −x−2, −y+2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PV2160).

References

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  • Pan, X. H., Liu, X., Zhao, B. X., Xie, Y. S., Shin, D. S., Zhang, S. L., Zhao, J. & Miao, J. Y. (2008). Bioorg. Med. Chem 16, 9093–9100. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Szabó, G.; Fischer, J.; Kis-Varga, Á. & Gyires, K. (2008). J Med. Chem.51, 142–147. [PubMed]
  • Xie, Y. S., Pan, X. H., Zhao, B. X., Liu, J. T., Shin, D. S., Zhang, J. H., Zheng, L. W., Zhao, J. & Miao, J. Y. (2008). J. Organomet. Chem 693, 1367–1374.
  • Zhang, J. H., Fan, C. D., Zhao, B. X., Shin, D. S., Dong, W. L., Xie, Y. S. & Miao, J. Y. (2008). Bioorg. Med. Chem 16, 10165–10171. [PubMed]

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