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The title compound, C20H26N2O5, was prepared in good yield (76%) through condensation of diethyl (4-meth­oxy­benz­yl)propane­dioate with 3,5-dimethyl-1H-pyrazole. The dihedral between the benzene and pyrazole rings is 83.96 (10)°. The crystal packing is stabilized by a C—H...O inter­action, which links the mol­ecules into centrosymmetric dimers.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536810025572/bt5280sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536810025572/bt5280Isup2.hkl
Contains datablock I

CCDC reference: 788358

Key indicators

  • Single-crystal X-ray study
  • T = 296 K, P = 0.0 kPa
  • Mean [sigma](C-C) = 0.003 Å
  • R factor = 0.056
  • wR factor = 0.154
  • Data-to-parameter ratio = 15.7

checkCIF/PLATON results

No syntax errors found



Alert level C DIFMX01_ALERT_2_C The maximum difference density is > 0.1*ZMAX*0.75 _refine_diff_density_max given = 0.680 Test value = 0.600 DIFMX02_ALERT_1_C The maximum difference density is > 0.1*ZMAX*0.75 The relevant atom site should be identified. PLAT097_ALERT_2_C Large Reported Max. (Positive) Residual Density 0.68 eA-3 PLAT220_ALERT_2_C Large Non-Solvent C Ueq(max)/Ueq(min) ... 3.17 Ratio PLAT360_ALERT_2_C Short C(sp3)-C(sp3) Bond C7 - C8 ... 1.42 Ang. PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) ..... 3
Alert level G PLAT793_ALERT_4_G The Model has Chirality at C1 (Verify) .... R
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 6 ALERT level C = Check and explain 1 ALERT level G = General alerts; check 1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 4 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check

Comment top

For the rational design of new HIV-1 Integrase (H—I) inhibitors, one validated target for chemotherapeutic intervention (Dayam et al., 2007), is fundamentally based on intermolecular coordination between H—I / chemical inhibitor / metals (Mg+2 and Mn+2, co-factors of the enzyme), leading to the formation of bimetallic complexes (Zeng et al., 2008; Sechi et al., 2009). Thereby, several bimetallic metal complexes, in many cases exploring the known-well polydentate ligands, appear in this scenario as the most promising concept to be employed in either enzyme / drug interaction or electron transfer process, in the last case involving the biological oxygen transfer (Sechi et al., 2009; Ramkumar et al., 2008). Another exciting example of application for such polydentate ligands involves the synergic water activation, that occurs via the so-called -remote metallic atoms. Such organometallic compounds are structurally deemed to promote or block the H—I activity (Zeng et al., 2008).

In the molecule of the title compound (Fig.1), the dihedral angle between the planes of the pheny and the pyrazol ring is 83.96 (10)°.

Related literature top

For related compounds displaying biological activity, see: Dayam et al. (2007); Patil et al. (2007); Ramkumar et al. (2008); Sechi et al. (2009) & Zeng et al. (2008). For the synthetic procedure, see: Pommier & Neamati (2006).

Experimental top

To a solution of the diethyl (4-methoxybenzyl)propanedioate (5 mmol) in water (20 ml) was added the 3,5-dimethyl-1H-pyrazole (6 mmol) and the mixture and the stirring was continued at room temperature until the complete consume of the starting material. After removing solvent, the crude products were dissolved in diethyl ether (2x40 ml) and washed with water until the pH became neutral. The organic solvent was dried with sodium sulfate and then evaporated to give the pure compound (I) with 76% yield.. White crystals are obtained by recrystallization in ether/hexane (2/1).

Suitable single-crystal of malonate derivative (I) was obtained by recrystallization from ethanol. A white-transparent crystal was mounted on a glass fibre.

Refinement top

All H atoms attached to C atoms were fixed geometrically and treated as riding with C—H = 0.96 Å (methyl), C—H = 0.93 Å (aromatic), 0.97 Å (methylene) and 0.98 Å (methine) with Uiso(H) = 1.2Ueq or Uiso(H) = 1.5Ueq(methyl).

Structure description top

For the rational design of new HIV-1 Integrase (H—I) inhibitors, one validated target for chemotherapeutic intervention (Dayam et al., 2007), is fundamentally based on intermolecular coordination between H—I / chemical inhibitor / metals (Mg+2 and Mn+2, co-factors of the enzyme), leading to the formation of bimetallic complexes (Zeng et al., 2008; Sechi et al., 2009). Thereby, several bimetallic metal complexes, in many cases exploring the known-well polydentate ligands, appear in this scenario as the most promising concept to be employed in either enzyme / drug interaction or electron transfer process, in the last case involving the biological oxygen transfer (Sechi et al., 2009; Ramkumar et al., 2008). Another exciting example of application for such polydentate ligands involves the synergic water activation, that occurs via the so-called -remote metallic atoms. Such organometallic compounds are structurally deemed to promote or block the H—I activity (Zeng et al., 2008).

In the molecule of the title compound (Fig.1), the dihedral angle between the planes of the pheny and the pyrazol ring is 83.96 (10)°.

For related compounds displaying biological activity, see: Dayam et al. (2007); Patil et al. (2007); Ramkumar et al. (2008); Sechi et al. (2009) & Zeng et al. (2008). For the synthetic procedure, see: Pommier & Neamati (2006).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); 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: publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound with the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radii.
[Figure 2] Fig. 2. Partial packing view showing the chain generated by C—H···O hydrogen bonds shown as dashed lines. Symmetry code for generating the second molecule: 1 - x,-y,1 - z.
[Figure 3] Fig. 3. View of the title compound showing displacement ellipsoids at the 50% probability level.
Diethyl 2-[(3,5-dimethyl-1H-pyrazol-1-yl)(4-methoxyphenyl)methyl]propanedioate top
Crystal data top
C20H26N2O5F(000) = 800
Mr = 374.43Dx = 1.243 Mg m3
Monoclinic, P21/cMelting point: 361 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 11.9618 (3) ÅCell parameters from 2174 reflections
b = 7.9681 (2) Åθ = 2.3–27.1°
c = 21.1269 (6) ŵ = 0.09 mm1
β = 96.504 (1)°T = 296 K
V = 2000.70 (9) Å3Block, colourless
Z = 40.23 × 0.17 × 0.14 mm
Data collection top
Bruker X8 APEXII CCD area-detector
diffractometer
3177 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.027
Graphite monochromatorθmax = 26.0°, θmin = 2.7°
φ and ω scansh = 1414
18616 measured reflectionsk = 99
3921 independent reflectionsl = 2626
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.056Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.154H-atom parameters constrained
S = 1.05 w = 1/[σ2(Fo2) + (0.0687P)2 + 1.8319P]
where P = (Fo2 + 2Fc2)/3
3921 reflections(Δ/σ)max = 0.007
249 parametersΔρmax = 0.68 e Å3
0 restraintsΔρmin = 0.45 e Å3
Crystal data top
C20H26N2O5V = 2000.70 (9) Å3
Mr = 374.43Z = 4
Monoclinic, P21/cMo Kα radiation
a = 11.9618 (3) ŵ = 0.09 mm1
b = 7.9681 (2) ÅT = 296 K
c = 21.1269 (6) Å0.23 × 0.17 × 0.14 mm
β = 96.504 (1)°
Data collection top
Bruker X8 APEXII CCD area-detector
diffractometer
3177 reflections with I > 2σ(I)
18616 measured reflectionsRint = 0.027
3921 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0560 restraints
wR(F2) = 0.154H-atom parameters constrained
S = 1.05Δρmax = 0.68 e Å3
3921 reflectionsΔρmin = 0.45 e Å3
249 parameters
Special details top

Experimental. The data collection nominally covered a sphere of reciprocal space, by a combination of tree sets of exposures; each set had a different φ angle for the crystal and each exposure covered 0.5° in ω and 20 s in time. The crystal-to-detector distance was 37.5 mm.

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
xyzUiso*/Ueq
O20.40914 (11)0.14261 (19)0.44322 (7)0.0301 (3)
O30.26937 (12)0.19794 (18)0.36564 (7)0.0321 (4)
O40.39768 (14)0.2442 (2)0.36381 (8)0.0441 (4)
O50.23951 (15)0.1580 (2)0.30637 (7)0.0446 (4)
O10.16987 (15)0.2065 (2)0.68944 (8)0.0468 (5)
N10.25069 (14)0.3219 (2)0.47437 (8)0.0252 (4)
N20.15274 (14)0.3525 (2)0.43620 (8)0.0297 (4)
C10.29918 (16)0.1528 (2)0.47752 (9)0.0230 (4)
H10.38130.16330.48450.028*
C20.26772 (16)0.0673 (3)0.41296 (9)0.0244 (4)
H20.18590.05410.40510.029*
C110.26097 (16)0.0542 (2)0.53261 (9)0.0229 (4)
C30.32439 (16)0.1032 (2)0.41081 (9)0.0239 (4)
C120.33950 (17)0.0251 (3)0.57616 (9)0.0277 (4)
H120.41540.01970.57060.033*
C210.28468 (17)0.4563 (3)0.51094 (10)0.0285 (5)
C160.14790 (16)0.0419 (3)0.54174 (10)0.0277 (4)
H160.09410.09290.51270.033*
C130.30680 (18)0.1116 (3)0.62736 (10)0.0323 (5)
H130.36050.16430.65590.039*
C140.19347 (18)0.1206 (3)0.63658 (10)0.0311 (5)
C150.11364 (17)0.0445 (3)0.59307 (10)0.0312 (5)
H150.03760.05150.59830.037*
C60.30985 (19)0.1697 (3)0.35912 (10)0.0308 (5)
C230.12710 (18)0.5105 (3)0.44907 (11)0.0322 (5)
C40.32363 (19)0.3556 (3)0.35159 (12)0.0370 (5)
H4A0.26790.43290.33140.044*
H4B0.35750.40630.39090.044*
C220.20634 (18)0.5797 (3)0.49546 (10)0.0330 (5)
H220.20600.68740.51240.040*
C50.4121 (2)0.3243 (4)0.30837 (11)0.0466 (6)
H5A0.37890.26930.27040.070*
H5B0.44420.42920.29730.070*
H5C0.46990.25420.32960.070*
C250.3888 (2)0.4563 (3)0.55689 (12)0.0416 (6)
H25A0.37430.40000.59530.062*
H25B0.41140.56990.56660.062*
H25C0.44780.39900.53840.062*
C70.2781 (3)0.2351 (4)0.24975 (12)0.0612 (8)
H7A0.26950.35600.25150.073*
H7B0.35710.20980.24810.073*
C240.0258 (2)0.5924 (3)0.41410 (14)0.0489 (7)
H24A0.04930.67220.38420.073*
H24B0.01600.64900.44390.073*
H24C0.02090.50860.39170.073*
C170.0566 (2)0.2040 (4)0.70479 (13)0.0545 (7)
H17A0.03350.09000.71010.082*
H17B0.05210.26490.74360.082*
H17C0.00810.25540.67090.082*
C80.2127 (3)0.1700 (5)0.19471 (13)0.0731 (10)
H8A0.22450.05110.19220.110*
H8B0.23510.22300.15730.110*
H8C0.13450.19190.19750.110*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O20.0249 (7)0.0292 (8)0.0357 (8)0.0049 (6)0.0007 (6)0.0048 (6)
O30.0317 (8)0.0265 (8)0.0371 (8)0.0009 (6)0.0005 (6)0.0089 (6)
O40.0466 (10)0.0436 (10)0.0435 (9)0.0125 (8)0.0117 (8)0.0046 (8)
O50.0624 (11)0.0441 (10)0.0264 (8)0.0085 (8)0.0010 (7)0.0036 (7)
O10.0475 (10)0.0586 (12)0.0360 (9)0.0031 (9)0.0117 (7)0.0143 (8)
N10.0258 (8)0.0229 (9)0.0265 (8)0.0027 (7)0.0013 (7)0.0005 (7)
N20.0280 (9)0.0278 (9)0.0330 (9)0.0061 (7)0.0015 (7)0.0008 (7)
C10.0216 (9)0.0196 (9)0.0277 (10)0.0025 (7)0.0022 (7)0.0011 (8)
C20.0221 (9)0.0238 (10)0.0273 (10)0.0019 (8)0.0031 (8)0.0012 (8)
C110.0242 (9)0.0203 (10)0.0246 (9)0.0011 (8)0.0036 (7)0.0037 (7)
C30.0230 (10)0.0237 (10)0.0257 (9)0.0028 (8)0.0067 (8)0.0018 (8)
C120.0228 (10)0.0311 (11)0.0287 (10)0.0005 (8)0.0009 (8)0.0014 (8)
C210.0320 (11)0.0253 (11)0.0294 (10)0.0012 (8)0.0088 (8)0.0025 (8)
C160.0242 (10)0.0293 (11)0.0292 (10)0.0060 (8)0.0014 (8)0.0008 (8)
C130.0315 (11)0.0372 (13)0.0268 (10)0.0019 (9)0.0022 (8)0.0033 (9)
C140.0379 (12)0.0310 (12)0.0253 (10)0.0017 (9)0.0073 (9)0.0011 (8)
C150.0255 (10)0.0350 (12)0.0340 (11)0.0006 (9)0.0078 (8)0.0019 (9)
C60.0405 (12)0.0244 (11)0.0277 (10)0.0041 (9)0.0041 (9)0.0028 (8)
C230.0340 (11)0.0253 (11)0.0385 (11)0.0075 (9)0.0100 (9)0.0030 (9)
C40.0369 (12)0.0279 (11)0.0454 (13)0.0010 (9)0.0015 (10)0.0159 (10)
C220.0401 (12)0.0222 (10)0.0384 (12)0.0037 (9)0.0122 (10)0.0033 (9)
C50.0504 (15)0.0548 (16)0.0350 (12)0.0052 (12)0.0069 (11)0.0127 (12)
C250.0425 (13)0.0381 (13)0.0423 (13)0.0001 (11)0.0034 (10)0.0091 (11)
C70.097 (2)0.0572 (18)0.0293 (13)0.0235 (17)0.0078 (14)0.0054 (12)
C240.0432 (14)0.0413 (15)0.0613 (16)0.0180 (11)0.0019 (12)0.0046 (13)
C170.0596 (17)0.0595 (18)0.0492 (15)0.0086 (14)0.0274 (13)0.0059 (13)
C80.113 (3)0.072 (2)0.0346 (14)0.033 (2)0.0104 (16)0.0004 (14)
Geometric parameters (Å, º) top
O2—C31.199 (2)C13—H130.9300
O3—C31.331 (2)C14—C151.388 (3)
O3—C41.460 (3)C15—H150.9300
O4—C61.201 (3)C23—C221.397 (3)
O5—C61.322 (3)C23—C241.496 (3)
O5—C71.465 (3)C4—C51.495 (3)
O1—C141.367 (3)C4—H4A0.9700
O1—C171.428 (3)C4—H4B0.9700
N1—C211.355 (3)C22—H220.9300
N1—N21.367 (2)C5—H5A0.9600
N1—C11.466 (2)C5—H5B0.9600
N2—C231.331 (3)C5—H5C0.9600
C1—C111.517 (3)C25—H25A0.9600
C1—C21.533 (3)C25—H25B0.9600
C1—H10.9800C25—H25C0.9600
C2—C31.521 (3)C7—C81.424 (4)
C2—C61.531 (3)C7—H7A0.9700
C2—H20.9800C7—H7B0.9700
C11—C121.390 (3)C24—H24A0.9600
C11—C161.391 (3)C24—H24B0.9600
C12—C131.376 (3)C24—H24C0.9600
C12—H120.9300C17—H17A0.9600
C21—C221.372 (3)C17—H17B0.9600
C21—C251.490 (3)C17—H17C0.9600
C16—C151.385 (3)C8—H8A0.9600
C16—H160.9300C8—H8B0.9600
C13—C141.393 (3)C8—H8C0.9600
C3—O3—C4116.03 (16)N2—C23—C24120.3 (2)
C6—O5—C7115.4 (2)C22—C23—C24128.4 (2)
C14—O1—C17117.87 (19)O3—C4—C5110.0 (2)
C21—N1—N2112.18 (17)O3—C4—H4A109.7
C21—N1—C1127.50 (16)C5—C4—H4A109.7
N2—N1—C1119.92 (16)O3—C4—H4B109.7
C23—N2—N1104.46 (17)C5—C4—H4B109.7
N1—C1—C11111.05 (15)H4A—C4—H4B108.2
N1—C1—C2108.18 (15)C21—C22—C23105.97 (19)
C11—C1—C2112.80 (16)C21—C22—H22127.0
N1—C1—H1108.2C23—C22—H22127.0
C11—C1—H1108.2C4—C5—H5A109.5
C2—C1—H1108.2C4—C5—H5B109.5
C3—C2—C6105.57 (15)H5A—C5—H5B109.5
C3—C2—C1110.98 (16)C4—C5—H5C109.5
C6—C2—C1110.86 (16)H5A—C5—H5C109.5
C3—C2—H2109.8H5B—C5—H5C109.5
C6—C2—H2109.8C21—C25—H25A109.5
C1—C2—H2109.8C21—C25—H25B109.5
C12—C11—C16118.10 (18)H25A—C25—H25B109.5
C12—C11—C1120.23 (17)C21—C25—H25C109.5
C16—C11—C1121.66 (17)H25A—C25—H25C109.5
O2—C3—O3125.32 (19)H25B—C25—H25C109.5
O2—C3—C2124.59 (18)C8—C7—O5108.6 (2)
O3—C3—C2110.01 (16)C8—C7—H7A110.0
C13—C12—C11121.13 (19)O5—C7—H7A110.0
C13—C12—H12119.4C8—C7—H7B110.0
C11—C12—H12119.4O5—C7—H7B110.0
N1—C21—C22106.12 (18)H7A—C7—H7B108.3
N1—C21—C25123.09 (19)C23—C24—H24A109.5
C22—C21—C25130.8 (2)C23—C24—H24B109.5
C15—C16—C11121.46 (19)H24A—C24—H24B109.5
C15—C16—H16119.3C23—C24—H24C109.5
C11—C16—H16119.3H24A—C24—H24C109.5
C12—C13—C14120.21 (19)H24B—C24—H24C109.5
C12—C13—H13119.9O1—C17—H17A109.5
C14—C13—H13119.9O1—C17—H17B109.5
O1—C14—C15124.7 (2)H17A—C17—H17B109.5
O1—C14—C13115.74 (19)O1—C17—H17C109.5
C15—C14—C13119.52 (19)H17A—C17—H17C109.5
C16—C15—C14119.56 (19)H17B—C17—H17C109.5
C16—C15—H15120.2C7—C8—H8A109.5
C14—C15—H15120.2C7—C8—H8B109.5
O4—C6—O5124.9 (2)H8A—C8—H8B109.5
O4—C6—C2124.10 (19)C7—C8—H8C109.5
O5—C6—C2110.92 (18)H8A—C8—H8C109.5
N2—C23—C22111.27 (19)H8B—C8—H8C109.5
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C12—H12···O2i0.932.513.358 (3)152
Symmetry code: (i) x+1, y, z+1.

Experimental details

Crystal data
Chemical formulaC20H26N2O5
Mr374.43
Crystal system, space groupMonoclinic, P21/c
Temperature (K)296
a, b, c (Å)11.9618 (3), 7.9681 (2), 21.1269 (6)
β (°) 96.504 (1)
V3)2000.70 (9)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.23 × 0.17 × 0.14
Data collection
DiffractometerBruker X8 APEXII CCD area-detector
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
18616, 3921, 3177
Rint0.027
(sin θ/λ)max1)0.617
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.056, 0.154, 1.05
No. of reflections3921
No. of parameters249
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.68, 0.45

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C12—H12···O2i0.932.513.358 (3)152
Symmetry code: (i) x+1, y, z+1.
 

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