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Acta Crystallogr Sect E Struct Rep Online. 2008 August 1; 64(Pt 8): o1439.
Published online 2008 July 9. doi:  10.1107/S1600536808020722
PMCID: PMC2962070

2-Methoxy­phenyl 2-{2-[1-methyl-5-(4-methyl­benzo­yl)pyrrol-2-yl]acetamido}acetate

Abstract

The title compound, amtolmetin guacil, C24H24N2O5, is a new gastroprotective non-steroidal anti-inflammatory drug. In the crystal structure, the drug mol­ecule is linked into a one-dimensional structure along the c axis by weak N—H(...)O inter­actions between the amide groups. C—H(...)O and C—H(...)π inter­actions influence the packing.

Related literature

For background, see: Tubaro et al. (2000 [triangle]); Vippagunta et al. (2001 [triangle]).

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Object name is e-64-o1439-scheme1.jpg

Experimental

Crystal data

  • C24H24N2O5
  • M r = 420.45
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1439-efi1.jpg
  • a = 11.307 (3) Å
  • b = 19.768 (7) Å
  • c = 9.713 (3) Å
  • V = 2170.9 (12) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 (2) K
  • 0.30 × 0.25 × 0.20 mm

Data collection

  • Rigaku Weissenberg IP diffractometer
  • Absorption correction: none
  • 19812 measured reflections
  • 2626 independent reflections
  • 1938 reflections with I > 2σ(I)
  • R int = 0.085

Refinement

  • R[F 2 > 2σ(F 2)] = 0.068
  • wR(F 2) = 0.109
  • S = 1.12
  • 2626 reflections
  • 284 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.13 e Å−3
  • Δρmin = −0.17 e Å−3

Data collection: TEXRAY (Molecular Structure Corporation, 1999 [triangle]); cell refinement: TEXRAY; data reduction: TEXSAN (Molecular Structure Corporation, 1999 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: X-SEED (Barbour, 2001 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bonding geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808020722/bv2099sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808020722/bv2099Isup2.hkl

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

Acknowledgments

The authors acknowledge support from the Project of the Natural Science Foundation of Fujian Province, China (grant No. E0610024), the Research Project of the Education Bureau of Fujian Province, China (grant No. JA06052) and the Project of the Fuzhou Municipal Bureau of Science and Technology (grant No. 2007-Z-81).

supplementary crystallographic information

Comment

A current focus of research in solid state drug design is to understand polymorphism at the molecular level (Vippagunta et al., 2001). Amtolmetin guacil is a new gastroprotective nonsteroidal anti-inflammatory drug (Tubaro et al., 2000). In this contribution, we report its crystal structure which is unknown till now.

In the crystal structure, there exist weak hydrogen bonding interactions (N1—H1···O4) between the amide group of amtolmetin guacil which connect drug molecules into a one-dimensional structure along c axis. There also exist weak C—H···O interactions within the one-dimensional structure (C11—H11B···O4; C14—H14···O1; C19—H19··· O3; Table 1). The C—H···O interactions and C—H···π interactions (C24—H24A···O3; C13—H13···Cg1; Table 1) give rise to the packing structure (Fig.2)

Experimental

Amtolmetin guacil (105 mg, 0.25 mmol) was dissolved in ethanol (20 ml) and the solution was kept in air and after several days colorless crystals were obtained.

Refinement

All H atoms were located geometrically (C—H = 0.95–0.99 Å, N—H = 0.88 Å) with Uiso(H) = 1.2 Ueq(C,N) or 1.5 Ueq(C).

Figures

Fig. 1.
ORTEP of (I) with 50% thermal ellipsoids.
Fig. 2.
The packing structure viewed along c axis. The dashed lines indicate C—H···O or C—H···π interactions

Crystal data

C24H24N2O5F000 = 888
Mr = 420.45Dx = 1.286 Mg m3
Orthorhombic, Pna21Mo Kα radiation λ = 0.71073 Å
Hall symbol: P2c-2nCell parameters from 19812 reflections
a = 11.307 (3) Åθ = 3.5–27.5º
b = 19.768 (7) ŵ = 0.09 mm1
c = 9.713 (3) ÅT = 293 (2) K
V = 2170.9 (12) Å3Block, colorless
Z = 40.30 × 0.25 × 0.20 mm

Data collection

Rigaku Weissenberg IP diffractometer1938 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.085
Monochromator: graphiteθmax = 27.5º
T = 293(2) Kθmin = 3.5º
scintillation counter scansh = −14→14
Absorption correction: nonek = −25→25
19812 measured reflectionsl = −12→12
2626 independent reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.068H-atom parameters constrained
wR(F2) = 0.109  w = 1/[σ2(Fo2) + (0.0337P)2 + 0.5426P] where P = (Fo2 + 2Fc2)/3
S = 1.12(Δ/σ)max < 0.001
2626 reflectionsΔρmax = 0.13 e Å3
284 parametersΔρmin = −0.17 e Å3
1 restraintExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0111 (12)

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
O1−0.0274 (2)0.40855 (14)0.2773 (3)0.0591 (8)
O20.1174 (2)0.48242 (13)0.4332 (4)0.0637 (8)
O30.2659 (2)0.40913 (14)0.4028 (4)0.0647 (9)
O40.4775 (2)0.51742 (15)0.4870 (3)0.0595 (8)
O50.7830 (4)0.75559 (16)0.3571 (4)0.0995 (13)
N10.4020 (2)0.51066 (16)0.2744 (3)0.0481 (8)
H10.41470.50280.18640.058*
N20.6986 (2)0.61548 (15)0.3541 (3)0.0438 (7)
C1−0.1080 (4)0.3716 (3)0.1921 (5)0.0747 (14)
H1A−0.08880.32330.19600.112*
H1B−0.10160.38760.09690.112*
H1C−0.18900.37870.22520.112*
C2−0.0308 (3)0.39568 (19)0.4136 (5)0.0469 (9)
C3−0.1055 (3)0.35013 (19)0.4785 (5)0.0547 (11)
H3−0.15900.32390.42510.066*
C4−0.1032 (4)0.3424 (2)0.6190 (5)0.0676 (13)
H4−0.15520.31110.66200.081*
C5−0.0266 (4)0.3793 (3)0.6973 (5)0.0721 (13)
H5−0.02540.37350.79440.086*
C60.0490 (4)0.4250 (2)0.6363 (5)0.0678 (13)
H60.10210.45090.69070.081*
C70.0467 (3)0.43263 (19)0.4957 (5)0.0505 (10)
C80.2255 (3)0.4638 (2)0.3893 (4)0.0464 (9)
C90.2833 (3)0.5239 (2)0.3221 (4)0.0538 (10)
H9A0.23440.53850.24290.065*
H9B0.28560.56180.38880.065*
C100.4926 (3)0.51018 (18)0.3624 (4)0.0448 (9)
C110.6148 (3)0.5008 (2)0.3026 (4)0.0478 (10)
H11A0.64070.45330.31530.057*
H11B0.61350.51060.20270.057*
C120.6995 (3)0.54758 (17)0.3735 (4)0.0402 (8)
C130.7776 (3)0.53269 (19)0.4760 (4)0.0456 (9)
H130.79760.48880.50840.055*
C140.8228 (3)0.59397 (19)0.5247 (4)0.0486 (10)
H140.87790.59930.59780.058*
C150.7734 (3)0.64510 (18)0.4483 (4)0.0458 (9)
C160.6281 (4)0.6504 (2)0.2510 (4)0.0677 (13)
H16A0.67370.65440.16560.102*
H16B0.60740.69560.28470.102*
H16C0.55560.62460.23320.102*
C170.7972 (4)0.7178 (2)0.4555 (4)0.0581 (11)
C180.8422 (3)0.74440 (19)0.5879 (4)0.0483 (9)
C190.8074 (3)0.71810 (18)0.7124 (4)0.0482 (10)
H190.75390.68110.71450.058*
C200.8493 (3)0.74480 (19)0.8353 (4)0.0512 (10)
H200.82440.72580.92040.061*
C210.9197 (4)0.79965 (19)0.5888 (5)0.0576 (11)
H210.94350.81950.50420.069*
C220.9615 (3)0.8255 (2)0.7100 (5)0.0580 (11)
H221.01520.86240.70800.070*
C230.9273 (3)0.79901 (19)0.8349 (5)0.0529 (10)
C240.9719 (5)0.8269 (2)0.9692 (5)0.0820 (16)
H24A1.05460.84080.95880.123*
H24B0.96620.79201.04060.123*
H24C0.92400.86610.99580.123*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0588 (17)0.0615 (18)0.0569 (18)−0.0087 (14)0.0102 (15)−0.0022 (15)
O20.0390 (13)0.0507 (15)0.101 (2)−0.0013 (12)0.0066 (16)−0.0015 (17)
O30.0476 (15)0.0512 (17)0.096 (2)0.0026 (13)0.0111 (16)−0.0020 (16)
O40.0488 (15)0.091 (2)0.0383 (16)−0.0072 (15)0.0047 (13)−0.0114 (16)
O50.164 (3)0.065 (2)0.069 (2)−0.033 (2)−0.042 (3)0.0247 (19)
N10.0393 (17)0.064 (2)0.0406 (17)−0.0050 (15)−0.0003 (15)−0.0036 (16)
N20.0472 (16)0.0503 (18)0.0339 (16)−0.0026 (14)−0.0076 (15)0.0020 (15)
C10.058 (3)0.102 (4)0.064 (3)−0.004 (3)−0.003 (3)−0.008 (3)
C20.040 (2)0.043 (2)0.057 (3)0.0051 (17)0.011 (2)−0.0051 (19)
C30.048 (2)0.043 (2)0.073 (3)−0.0034 (18)0.012 (2)−0.007 (2)
C40.064 (3)0.063 (3)0.076 (4)0.006 (2)0.024 (3)0.012 (3)
C50.071 (3)0.087 (3)0.059 (3)0.013 (3)0.001 (3)0.012 (3)
C60.052 (3)0.079 (3)0.072 (3)0.002 (2)−0.008 (2)−0.009 (3)
C70.039 (2)0.045 (2)0.067 (3)0.0008 (18)0.007 (2)0.001 (2)
C80.0365 (18)0.050 (2)0.052 (2)−0.0055 (18)−0.0036 (18)−0.0102 (19)
C90.042 (2)0.061 (2)0.059 (3)0.0005 (19)−0.006 (2)0.002 (2)
C100.046 (2)0.050 (2)0.039 (2)−0.0093 (17)0.0015 (19)−0.0059 (19)
C110.045 (2)0.062 (2)0.036 (2)−0.0069 (18)−0.0002 (17)−0.0103 (18)
C120.0370 (17)0.050 (2)0.0338 (19)−0.0018 (16)0.0052 (16)−0.0062 (17)
C130.043 (2)0.046 (2)0.048 (2)0.0054 (17)−0.0036 (19)−0.0019 (18)
C140.042 (2)0.055 (2)0.048 (2)−0.0012 (18)−0.0135 (18)−0.002 (2)
C150.050 (2)0.048 (2)0.040 (2)−0.0054 (17)−0.0137 (19)−0.0016 (18)
C160.077 (3)0.071 (3)0.055 (3)−0.003 (2)−0.029 (2)0.015 (2)
C170.071 (3)0.052 (2)0.052 (3)−0.008 (2)−0.013 (2)0.008 (2)
C180.053 (2)0.038 (2)0.054 (2)−0.0030 (18)−0.007 (2)−0.001 (2)
C190.048 (2)0.0395 (19)0.058 (3)−0.0020 (16)−0.012 (2)0.000 (2)
C200.057 (2)0.046 (2)0.051 (2)0.0035 (19)−0.007 (2)−0.004 (2)
C210.060 (2)0.043 (2)0.070 (3)−0.007 (2)−0.002 (2)0.003 (2)
C220.057 (2)0.043 (2)0.075 (3)−0.0097 (18)−0.004 (3)−0.011 (2)
C230.052 (2)0.043 (2)0.063 (3)0.0061 (18)−0.021 (2)−0.012 (2)
C240.098 (4)0.069 (3)0.079 (3)−0.003 (3)−0.034 (3)−0.024 (3)

Geometric parameters (Å, °)

O1—C21.349 (5)C10—C111.511 (5)
O1—C11.431 (5)C11—C121.499 (5)
O2—C81.346 (4)C11—H11A0.9900
O2—C71.406 (5)C11—H11B0.9900
O3—C81.181 (4)C12—C131.363 (5)
O4—C101.230 (4)C13—C141.397 (5)
O5—C171.223 (5)C13—H130.9500
N1—C101.334 (5)C14—C151.372 (5)
N1—C91.443 (4)C14—H140.9500
N1—H10.8800C15—C171.464 (5)
N2—C121.355 (4)C16—H16A0.9800
N2—C151.377 (4)C16—H16B0.9800
N2—C161.454 (5)C16—H16C0.9800
C1—H1A0.9800C17—C181.479 (6)
C1—H1B0.9800C18—C191.374 (5)
C1—H1C0.9800C18—C211.400 (5)
C2—C31.386 (6)C19—C201.388 (6)
C2—C71.392 (6)C19—H190.9500
C3—C41.374 (6)C20—C231.388 (5)
C3—H30.9500C20—H200.9500
C4—C51.365 (7)C21—C221.367 (6)
C4—H40.9500C21—H210.9500
C5—C61.377 (7)C22—C231.376 (6)
C5—H50.9500C22—H220.9500
C6—C71.374 (6)C23—C241.504 (6)
C6—H60.9500C24—H24A0.9800
C8—C91.505 (5)C24—H24B0.9800
C9—H9A0.9900C24—H24C0.9800
C9—H9B0.9900
C2—O1—C1116.9 (3)C10—C11—H11B109.8
C8—O2—C7117.5 (3)H11A—C11—H11B108.2
C10—N1—C9120.6 (3)N2—C12—C13108.7 (3)
C10—N1—H1119.7N2—C12—C11122.9 (3)
C9—N1—H1119.7C13—C12—C11128.0 (3)
C12—N2—C15108.9 (3)C12—C13—C14107.3 (3)
C12—N2—C16124.7 (3)C12—C13—H13126.4
C15—N2—C16126.4 (3)C14—C13—H13126.4
O1—C1—H1A109.5C15—C14—C13107.9 (3)
O1—C1—H1B109.5C15—C14—H14126.1
H1A—C1—H1B109.5C13—C14—H14126.1
O1—C1—H1C109.5C14—C15—N2107.2 (3)
H1A—C1—H1C109.5C14—C15—C17128.5 (3)
H1B—C1—H1C109.5N2—C15—C17124.2 (3)
O1—C2—C3125.9 (4)N2—C16—H16A109.5
O1—C2—C7116.4 (4)N2—C16—H16B109.5
C3—C2—C7117.7 (4)H16A—C16—H16B109.5
C4—C3—C2120.8 (4)N2—C16—H16C109.5
C4—C3—H3119.6H16A—C16—H16C109.5
C2—C3—H3119.6H16B—C16—H16C109.5
C5—C4—C3120.4 (5)O5—C17—C15122.5 (4)
C5—C4—H4119.8O5—C17—C18120.5 (4)
C3—C4—H4119.8C15—C17—C18117.0 (3)
C4—C5—C6120.3 (5)C19—C18—C21117.9 (4)
C4—C5—H5119.9C19—C18—C17122.2 (3)
C6—C5—H5119.9C21—C18—C17119.9 (4)
C7—C6—C5119.3 (5)C18—C19—C20121.0 (3)
C7—C6—H6120.4C18—C19—H19119.5
C5—C6—H6120.4C20—C19—H19119.5
C6—C7—C2121.5 (4)C23—C20—C19120.5 (4)
C6—C7—O2119.7 (4)C23—C20—H20119.8
C2—C7—O2118.6 (4)C19—C20—H20119.8
O3—C8—O2124.5 (4)C22—C21—C18120.9 (4)
O3—C8—C9127.1 (3)C22—C21—H21119.5
O2—C8—C9108.4 (3)C18—C21—H21119.5
N1—C9—C8113.5 (3)C21—C22—C23121.3 (4)
N1—C9—H9A108.9C21—C22—H22119.4
C8—C9—H9A108.9C23—C22—H22119.4
N1—C9—H9B108.9C22—C23—C20118.4 (4)
C8—C9—H9B108.9C22—C23—C24122.1 (4)
H9A—C9—H9B107.7C20—C23—C24119.6 (4)
O4—C10—N1121.5 (4)C23—C24—H24A109.5
O4—C10—C11121.3 (3)C23—C24—H24B109.5
N1—C10—C11117.2 (3)H24A—C24—H24B109.5
C12—C11—C10109.4 (3)C23—C24—H24C109.5
C12—C11—H11A109.8H24A—C24—H24C109.5
C10—C11—H11A109.8H24B—C24—H24C109.5
C12—C11—H11B109.8

Table 1 Hydrogen-bonding geometry (A%, °). Cg1 is the centroid of the C2/C3–C7 ring.

D—H···AD—H (Å)H···A (Å)D···A (Å)D—H···A (°)
N1—H1···O4i0.882.323.1564157
C11—H11B···O4i0.992.403.2586145
C24—H24A···O3ii0.982.503.4418162
C14—H14··· O1iii0.952.433.3722170
C19—H19··· O3iii0.952.563.2300127
C13—H13··· Cg1iv0.952.853.6961150

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BV2099).

References

  • Barbour, L. J. (2001). J. Supramol. Chem.1, 189–191.
  • Molecular Structure Corporation (1999). TEXRAY and TEXSAN MSC, The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Tubaro, E., Belogi, L. & Mezzadri, C. M. (2000). Eur. J. Pharmacol.387, 233–244. [PubMed]
  • Vippagunta, S. R., Brittain, H. G. & Grant, D. J. W. (2001). Adv. Drug Deliv. Rev.48, 3–26. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography