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Acta Crystallogr Sect E Struct Rep Online. 2010 February 1; 66(Pt 2): o476.
Published online 2010 January 30. doi:  10.1107/S1600536809055688
PMCID: PMC2979880

4-[4-(3-Methoxy­benzamido)phen­oxy]-N-methyl­picolinamide

Abstract

In the title compound, C21H19N3O4, the central benzene ring makes dihedral angles of 78.54 (6) and 75.30 (6)° with the pyridine and 3-methoxy­phenyl rings, respectively. An intra­molecular N—H(...)N interaction occurs, generating an S(?). The crystal packing shows inter­molecular N—H(...)O hydrogen-bonding inter­actions between the N—H groups and the O atoms of the 3-methoxy­phenyl ring and the carbonyl groups of the amide functions. Inter­molecular C—H(...)O inter­actions are also present.

Related literature

For related compounds and their biological activity, see: Khire et al. (2004 [triangle]); Dominguez et al. (2007 [triangle]).

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Object name is e-66-0o476-scheme1.jpg

Experimental

Crystal data

  • C21H19N3O4
  • M r = 377.39
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o476-efi1.jpg
  • a = 5.0915 (10) Å
  • b = 8.3251 (17) Å
  • c = 11.611 (2) Å
  • α = 71.29 (3)°
  • β = 87.74 (3)°
  • γ = 76.10 (3)°
  • V = 452.14 (16) Å3
  • Z = 1
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 113 K
  • 0.34 × 0.29 × 0.19 mm

Data collection

  • Rigaku Saturn CCD area-detector diffractometer
  • Absorption correction: multi-scan (ABSCOR; Higashi, 1995 [triangle]) T min = 0.968, T max = 0.982
  • 3733 measured reflections
  • 2108 independent reflections
  • 1811 reflections with I > 2σ(I)
  • R int = 0.026

Refinement

  • R[F 2 > 2σ(F 2)] = 0.035
  • wR(F 2) = 0.085
  • S = 1.10
  • 2108 reflections
  • 263 parameters
  • 3 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.24 e Å−3

Data collection: CrystalClear (Rigaku/MSC, 2005 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809055688/om2308sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809055688/om2308Isup2.hkl

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

Acknowledgments

The project was sponsored by the Scientific Research Foundation for Returned Overseas Chinese Scholars (No. 20071108–18–14), State Education Ministry. We thank the Analytical and Testing Center of Sichuan University for the X-ray measurements.

supplementary crystallographic information

Comment

Sorafenib is of great importance owing to its antitumor properties (Khire et al., 2004; Dominguez et al., 2007). The title compound, as one of its derivatives, possessed even better in vitro anticancer activity against both two tumor cell lines (HCT116 and HEPG2). As a potent antitumor drug, we report here its crystal structure.

In the title molecule, C21H19N3O4, (Fig.1), the phenyl ring makes dihedral angles of 78.54 (6)° and 75.30 (6)° with the pyridine ring and the 3-methoxyphenyl ring, respectively. In the crystal structure, intermolecular N—H···O hydrogen-bonding interactions between the N—H and O atoms of 3-methoxyphenyl ring and carbonyl groups of the amide functionalities form an infinite three-dimensional structure (Table 1 and Fig. 2).

Experimental

To the suspension of anhydrous potassium carbonate (1.635 g,12.5 mmol) and 4-(4-aminophenoxy)-N-methylpicolinamide (1.22 g, 5 mmol) in 11.4 ml THF was added dropwise 3-methoxybenzoyl chloride(1.28 g,7.5 mmol). After being stirred at room temperature for 2 h, the mixture was extracted with 90 ml EA and 30 ml water for three times and the combined organic layers were dried over anhydrous Na2SO4. Then the solution was concentrated under vacuum, and the residue was recrystallized from ethanol to give the title compound. Crystals suitable for X-ray analysis were obtained by slow evaporation from a solution of ethanol.

Refinement

The two H atoms of N1 and N3 were located in a difference map and refined isotropically. The reminaing H atoms were positioned geometrically (C—H = 0.95–0.98 Å) and refined using a riding model, with Uiso(H) = 1.2–1.5Ueq(C). In the final stages of refinement, Friedel-pair reflections were merged.

Figures

Fig. 1.
The molecular structure of the title compound, with displacement ellipsoids drawn at the 30% probability level.
Fig. 2.
The cell packing of the title compound.

Crystal data

C21H19N3O4Z = 1
Mr = 377.39F(000) = 198
Triclinic, P1Dx = 1.386 Mg m3
a = 5.0915 (10) ÅMo Kα radiation, λ = 0.71073 Å
b = 8.3251 (17) ÅCell parameters from 1652 reflections
c = 11.611 (2) Åθ = 2.7–27.8°
α = 71.29 (3)°µ = 0.10 mm1
β = 87.74 (3)°T = 113 K
γ = 76.10 (3)°Block, colourless
V = 452.14 (16) Å30.34 × 0.29 × 0.19 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer2108 independent reflections
Radiation source: rotating anode1811 reflections with I > 2σ(I)
confocalRint = 0.026
Detector resolution: 7.31 pixels mm-1θmax = 27.8°, θmin = 2.7°
ω and [var phi] scansh = −6→4
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)k = −10→10
Tmin = 0.968, Tmax = 0.982l = −14→15
3733 measured reflections

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)] = 0.035Hydrogen site location: mixed
wR(F2) = 0.085H atoms treated by a mixture of independent and constrained refinement
S = 1.10w = 1/[σ2(Fo2) + (0.0481P)2] where P = (Fo2 + 2Fc2)/3
2108 reflections(Δ/σ)max < 0.001
263 parametersΔρmax = 0.22 e Å3
3 restraintsΔρmin = −0.24 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
O1−0.3679 (3)1.5504 (2)0.23318 (15)0.0212 (4)
O2−0.1469 (3)0.9491 (2)0.56055 (17)0.0249 (4)
O30.4394 (3)0.1895 (2)0.81518 (15)0.0220 (4)
O41.1345 (3)0.2263 (2)1.10678 (16)0.0230 (4)
N10.3007 (3)0.9089 (2)0.60459 (17)0.0154 (4)
H1N0.443 (6)0.954 (4)0.579 (3)0.031 (8)*
N21.0377 (4)−0.1617 (2)1.06587 (18)0.0197 (4)
N31.3326 (4)−0.0601 (3)1.20340 (18)0.0202 (4)
H3N1.353 (6)−0.166 (4)1.208 (3)0.025 (7)*
C10.0404 (4)1.1969 (3)0.48677 (19)0.0138 (4)
C2−0.1555 (4)1.2811 (3)0.3920 (2)0.0157 (4)
H2−0.26831.21790.37130.019*
C3−0.1849 (4)1.4569 (3)0.3282 (2)0.0166 (5)
C4−0.0230 (4)1.5503 (3)0.3610 (2)0.0186 (5)
H4−0.04411.67110.31810.022*
C50.1675 (4)1.4670 (3)0.4559 (2)0.0196 (5)
H50.27541.53160.47840.024*
C60.2036 (4)1.2891 (3)0.5190 (2)0.0167 (5)
H60.33771.23180.58300.020*
C7−0.4855 (5)1.4516 (3)0.1769 (2)0.0240 (5)
H7A−0.60351.39020.23400.036*
H7B−0.34101.36630.15490.036*
H7C−0.59191.53100.10340.036*
C80.0553 (4)1.0091 (3)0.5533 (2)0.0163 (4)
C90.3486 (4)0.7259 (3)0.66625 (19)0.0145 (4)
C100.5761 (4)0.6131 (3)0.6406 (2)0.0162 (4)
H100.70460.65890.58650.019*
C110.6152 (4)0.4336 (3)0.6942 (2)0.0190 (5)
H110.76890.35600.67630.023*
C120.4271 (4)0.3690 (3)0.7740 (2)0.0174 (5)
C130.2105 (4)0.4795 (3)0.8055 (2)0.0213 (5)
H130.08920.43360.86400.026*
C140.1710 (4)0.6586 (3)0.7512 (2)0.0204 (5)
H140.02150.73560.77230.025*
C150.6403 (4)0.0792 (3)0.8978 (2)0.0169 (5)
C160.6760 (5)−0.0977 (3)0.9182 (2)0.0194 (5)
H160.5661−0.13940.87570.023*
C170.8763 (5)−0.2126 (3)1.0024 (2)0.0210 (5)
H170.9012−0.33411.01610.025*
C180.9936 (4)0.0107 (3)1.0450 (2)0.0163 (4)
C190.8000 (4)0.1369 (3)0.9625 (2)0.0161 (4)
H190.77770.25780.95090.019*
C201.1623 (4)0.0692 (3)1.1206 (2)0.0172 (5)
C211.4960 (5)−0.0250 (3)1.2878 (2)0.0220 (5)
H21A1.39160.07331.31220.033*
H21B1.65980.00431.24840.033*
H21C1.5470−0.12881.35990.033*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0201 (8)0.0162 (9)0.0232 (9)−0.0018 (6)−0.0079 (6)−0.0016 (7)
O20.0138 (7)0.0175 (8)0.0376 (10)−0.0063 (6)−0.0052 (7)0.0017 (7)
O30.0228 (8)0.0134 (8)0.0260 (9)−0.0053 (6)−0.0103 (7)0.0010 (7)
O40.0243 (8)0.0170 (9)0.0262 (9)−0.0024 (6)−0.0048 (7)−0.0060 (7)
N10.0118 (8)0.0135 (9)0.0184 (9)−0.0030 (7)0.0003 (7)−0.0017 (8)
N20.0229 (10)0.0139 (10)0.0209 (10)−0.0021 (7)−0.0008 (8)−0.0053 (8)
N30.0245 (10)0.0165 (11)0.0183 (10)−0.0019 (8)−0.0045 (8)−0.0054 (8)
C10.0115 (9)0.0125 (10)0.0163 (11)−0.0010 (7)0.0023 (8)−0.0047 (8)
C20.0125 (9)0.0155 (11)0.0195 (11)−0.0034 (8)0.0000 (8)−0.0059 (9)
C30.0138 (10)0.0149 (11)0.0180 (11)−0.0004 (8)−0.0001 (8)−0.0032 (9)
C40.0187 (11)0.0121 (11)0.0227 (12)−0.0029 (8)0.0017 (9)−0.0032 (9)
C50.0179 (11)0.0174 (12)0.0260 (13)−0.0069 (8)0.0007 (9)−0.0085 (10)
C60.0136 (10)0.0171 (12)0.0189 (11)−0.0029 (8)−0.0014 (8)−0.0056 (9)
C70.0237 (12)0.0198 (12)0.0272 (12)0.0009 (9)−0.0095 (10)−0.0088 (10)
C80.0139 (10)0.0159 (11)0.0174 (11)−0.0024 (8)0.0000 (8)−0.0038 (9)
C90.0134 (9)0.0137 (11)0.0142 (10)−0.0016 (8)−0.0038 (8)−0.0021 (8)
C100.0129 (10)0.0169 (11)0.0179 (11)−0.0037 (8)0.0012 (8)−0.0043 (9)
C110.0168 (10)0.0166 (11)0.0217 (11)−0.0005 (8)−0.0025 (9)−0.0057 (9)
C120.0200 (11)0.0130 (11)0.0164 (11)−0.0055 (8)−0.0073 (9)0.0010 (9)
C130.0188 (11)0.0206 (12)0.0206 (12)−0.0061 (8)0.0018 (9)−0.0006 (9)
C140.0177 (11)0.0209 (12)0.0185 (11)−0.0017 (8)0.0027 (8)−0.0031 (9)
C150.0168 (10)0.0147 (11)0.0146 (11)−0.0018 (8)−0.0010 (8)0.0002 (9)
C160.0229 (11)0.0179 (12)0.0190 (11)−0.0069 (9)0.0001 (8)−0.0064 (9)
C170.0276 (12)0.0116 (10)0.0220 (12)−0.0034 (8)0.0005 (9)−0.0040 (9)
C180.0182 (11)0.0152 (11)0.0143 (10)−0.0053 (8)0.0034 (8)−0.0027 (9)
C190.0189 (10)0.0131 (10)0.0147 (10)−0.0043 (8)0.0014 (8)−0.0021 (9)
C200.0155 (10)0.0195 (12)0.0162 (11)−0.0034 (8)0.0022 (8)−0.0060 (9)
C210.0206 (11)0.0253 (13)0.0203 (11)−0.0024 (9)−0.0031 (9)−0.0091 (10)

Geometric parameters (Å, °)

O1—C31.369 (3)C7—H7A0.9800
O1—C71.440 (3)C7—H7B0.9800
O2—C81.237 (3)C7—H7C0.9800
O3—C151.368 (3)C9—C141.387 (3)
O3—C121.402 (3)C9—C101.394 (3)
O4—C201.239 (3)C10—C111.389 (3)
N1—C81.360 (3)C10—H100.9500
N1—C91.424 (3)C11—C121.387 (3)
N1—H1N0.89 (3)C11—H110.9500
N2—C181.340 (3)C12—C131.376 (3)
N2—C171.346 (3)C13—C141.387 (3)
N3—C201.337 (3)C13—H130.9500
N3—C211.450 (3)C14—H140.9500
N3—H3N0.85 (3)C15—C161.382 (3)
C1—C61.391 (3)C15—C191.387 (3)
C1—C21.397 (3)C16—C171.386 (3)
C1—C81.491 (3)C16—H160.9500
C2—C31.386 (3)C17—H170.9500
C2—H20.9500C18—C191.387 (3)
C3—C41.397 (3)C18—C201.510 (3)
C4—C51.380 (3)C19—H190.9500
C4—H40.9500C21—H21A0.9800
C5—C61.396 (3)C21—H21B0.9800
C5—H50.9500C21—H21C0.9800
C6—H60.9500
C3—O1—C7116.81 (17)C11—C10—C9120.1 (2)
C15—O3—C12119.17 (17)C11—C10—H10120.0
C8—N1—C9122.98 (18)C9—C10—H10120.0
C8—N1—H1N116 (2)C12—C11—C10119.2 (2)
C9—N1—H1N118 (2)C12—C11—H11120.4
C18—N2—C17116.25 (18)C10—C11—H11120.4
C20—N3—C21121.4 (2)C13—C12—C11121.2 (2)
C20—N3—H3N122 (2)C13—C12—O3118.26 (19)
C21—N3—H3N117 (2)C11—C12—O3120.3 (2)
C6—C1—C2120.42 (19)C12—C13—C14119.4 (2)
C6—C1—C8122.61 (19)C12—C13—H13120.3
C2—C1—C8116.91 (19)C14—C13—H13120.3
C3—C2—C1119.96 (19)C13—C14—C9120.4 (2)
C3—C2—H2120.0C13—C14—H14119.8
C1—C2—H2120.0C9—C14—H14119.8
O1—C3—C2124.4 (2)O3—C15—C16116.9 (2)
O1—C3—C4115.84 (19)O3—C15—C19123.2 (2)
C2—C3—C4119.77 (19)C16—C15—C19119.86 (19)
C5—C4—C3120.0 (2)C15—C16—C17118.2 (2)
C5—C4—H4120.0C15—C16—H16120.9
C3—C4—H4120.0C17—C16—H16120.9
C4—C5—C6120.8 (2)N2—C17—C16123.7 (2)
C4—C5—H5119.6N2—C17—H17118.1
C6—C5—H5119.6C16—C17—H17118.1
C1—C6—C5119.04 (19)N2—C18—C19124.8 (2)
C1—C6—H6120.5N2—C18—C20116.87 (18)
C5—C6—H6120.5C19—C18—C20118.32 (19)
O1—C7—H7A109.5C18—C19—C15117.2 (2)
O1—C7—H7B109.5C18—C19—H19121.4
H7A—C7—H7B109.5C15—C19—H19121.4
O1—C7—H7C109.5O4—C20—N3124.1 (2)
H7A—C7—H7C109.5O4—C20—C18120.93 (19)
H7B—C7—H7C109.5N3—C20—C18115.0 (2)
O2—C8—N1122.4 (2)N3—C21—H21A109.5
O2—C8—C1120.97 (19)N3—C21—H21B109.5
N1—C8—C1116.65 (19)H21A—C21—H21B109.5
C14—C9—C10119.6 (2)N3—C21—H21C109.5
C14—C9—N1120.77 (18)H21A—C21—H21C109.5
C10—C9—N1119.64 (19)H21B—C21—H21C109.5
C6—C1—C2—C31.0 (3)C15—O3—C12—C13−113.2 (2)
C8—C1—C2—C3178.42 (18)C15—O3—C12—C1172.9 (3)
C7—O1—C3—C2−16.6 (3)C11—C12—C13—C143.7 (3)
C7—O1—C3—C4164.13 (19)O3—C12—C13—C14−170.2 (2)
C1—C2—C3—O1179.13 (19)C12—C13—C14—C9−0.3 (3)
C1—C2—C3—C4−1.6 (3)C10—C9—C14—C13−3.6 (3)
O1—C3—C4—C5−180.0 (2)N1—C9—C14—C13176.2 (2)
C2—C3—C4—C50.7 (3)C12—O3—C15—C16−168.06 (19)
C3—C4—C5—C60.8 (3)C12—O3—C15—C1913.8 (3)
C2—C1—C6—C50.5 (3)O3—C15—C16—C17−179.4 (2)
C8—C1—C6—C5−176.77 (19)C19—C15—C16—C17−1.1 (3)
C4—C5—C6—C1−1.4 (3)C18—N2—C17—C160.8 (3)
C9—N1—C8—O22.7 (3)C15—C16—C17—N20.3 (4)
C9—N1—C8—C1−177.13 (19)C17—N2—C18—C19−1.2 (3)
C6—C1—C8—O2149.6 (2)C17—N2—C18—C20176.7 (2)
C2—C1—C8—O2−27.7 (3)N2—C18—C19—C150.3 (3)
C6—C1—C8—N1−30.6 (3)C20—C18—C19—C15−177.45 (19)
C2—C1—C8—N1152.10 (19)O3—C15—C19—C18178.95 (19)
C8—N1—C9—C14−46.8 (3)C16—C15—C19—C180.8 (3)
C8—N1—C9—C10133.0 (2)C21—N3—C20—O41.9 (3)
C14—C9—C10—C114.1 (3)C21—N3—C20—C18−176.19 (19)
N1—C9—C10—C11−175.67 (19)N2—C18—C20—O4179.9 (2)
C9—C10—C11—C12−0.7 (3)C19—C18—C20—O4−2.2 (3)
C10—C11—C12—C13−3.2 (3)N2—C18—C20—N3−2.0 (3)
C10—C11—C12—O3170.56 (18)C19—C18—C20—N3175.94 (19)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1N···O2i0.89 (3)2.08 (3)2.918 (2)155 (3)
N3—H3N···O1ii0.85 (3)2.38 (3)3.148 (3)151 (2)
N3—H3N···N20.85 (3)2.33 (3)2.681 (3)105 (2)
C7—H7B···O4iii0.982.553.475 (3)158
C14—H14···O20.952.562.887 (3)100

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: OM2308).

References

  • Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.
  • Dominguez, C., Smith, L., Huang, Q., Yuan, C. & Ouyang, X. H. (2007). Bioorg. Med. Chem. Lett.17, 6003–6008. [PubMed]
  • Higashi, T. (1995). ABSCOR Rigaku Corporation, Tokyo, Japan.
  • Khire, U. R., Bankston, D., Barbosa, J., Brittelli, D. R. & Caringal, Y. (2004). Bioorg. Med. Chem. Lett.14, 783–786. [PubMed]
  • Rigaku/MSC (2005). CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

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