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Acta Crystallogr Sect E Struct Rep Online. 2010 January 1; 66(Pt 1): o205.
Published online 2009 December 19. doi:  10.1107/S1600536809054014
PMCID: PMC2980089

N-(3-Bromo-5-methyl-2-pyrid­yl)-4-methyl­benzene­sulfonamide

Abstract

In the mol­ecule of the title compound, C13H13BrN2O2S, the dihedral angle formed by the pyridine and benzene rings is 66.87 (3)°. An intra­molecular N—H(...)Br hydrogen bond is observed. In the crystal structure, N—H(...)O hydrogen bonds, C—H(...)π inter­actions and aromatic π–π stacking inter­actions [centroid–centroid distance = 3.757 (14) Å] link the mol­ecules into a three-dimensional network.

Related literature

The title compound is a key inter­mediate in the synthesis of new anti­tumor drugs including TGX221 [systematic name 7-methyl-2-(4-morpholinyl)-9-[1-(phenylamino)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one]. For the biological activity of TGX221, see: Jackson et al. (2005 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o205-scheme1.jpg

Experimental

Crystal data

  • C13H13BrN2O2S
  • M r = 341.22
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o205-efi1.jpg
  • a = 11.832 (2) Å
  • b = 13.305 (3) Å
  • c = 8.6263 (17) Å
  • β = 105.52 (3)°
  • V = 1308.5 (5) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 3.30 mm−1
  • T = 113 K
  • 0.22 × 0.21 × 0.18 mm

Data collection

  • Rigaku Saturn CCD area-detector diffractometer
  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 [triangle]) T min = 0.531, T max = 0.588
  • 10637 measured reflections
  • 3102 independent reflections
  • 2455 reflections with I > 2σ(I)
  • R int = 0.037

Refinement

  • R[F 2 > 2σ(F 2)] = 0.028
  • wR(F 2) = 0.071
  • S = 1.03
  • 3102 reflections
  • 178 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.38 e Å−3
  • Δρmin = −0.66 e Å−3

Data collection: DIFRAC (Gabe & White, 1993 [triangle]); cell refinement: DIFRAC; data reduction: NRCVAX (Gabe et al., 1989 [triangle]); 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]) and Mercury (Macrae et al., 2006 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809054014/rz2394sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809054014/rz2394Isup2.hkl

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

Acknowledgments

The authors thank Mr·Zhi-Hua Mao of Sichuan University for the X-ray data collection.

supplementary crystallographic information

Comment

TGX221, a selective inhibitor of PI3K p110β, and its derivatives are of great importance owing to their wide biological properties (Jackson et al., 2005). We report herein the crystal structure of the title compound, which is one of the key intermediates in our synthetic investigations of new antitumor drugs.

The molecular structure of the title compound is shown in Fig. 1. The dihedral angle between the benzene and pyridine is 66.87 (3)°. The molecular conformation is stabilized by an intramolecular N—H···Br hydrogen bond (Table 1). In the crystal, molecules are linked into a three-dimensional network by intermolecular N—H···O hydrogen bonds and aromatic π–π stacking interactions involving centrosymmetrically related pyridine and benzene rings, with a centroid-to-centroid distance of 3.757 (14) Å. In addition, C—H···π interactions are also present (Table 1; Cg1 is the centroid of the C7–C12 benzene ring).

Experimental

A mixture of 3-bromo-5-methylpyridin-2-amine (18.6 g, 0.1 mol), 4-methylbenzene-1-sulfonyl chloride (38.2 g, 0.2 mol), and pyridine (7.9 g, 0.10 mol), as a catalyst were charged into a three-necked round-bottomed flask fitted with a mechanical stirrer, a thermometer and a nitrogen inlet. The mixture was stirred vigorously at 100°C for 3 h. After the reactor was cooled to room temperature, the reaction solution was poured into water. The resulting solid was filtered, washed with water, dried and recrystallized from the mixture of hexane:ethyl acetate (3:1 v(v) to get colourless crystals suitable for X-ray analysis.

Refinement

The amine H atom was located in a difference Fourier map and refined freely. All other H atoms were positioned geometrically and refined using a riding model, with C—H = 0.95–0.98 Å and with Uiso(H) = 1.2 Ueq(C) or 1.5Ueq(C) for methyl H atoms.

Figures

Fig. 1.
The molecular structure of title compound showing 30% probability displacement ellipsoids and the atom-numbering scheme.

Crystal data

C13H13BrN2O2SF(000) = 688
Mr = 341.22Dx = 1.732 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4245 reflections
a = 11.832 (2) Åθ = 2.3–27.9°
b = 13.305 (3) ŵ = 3.30 mm1
c = 8.6263 (17) ÅT = 113 K
β = 105.52 (3)°Block, colourless
V = 1308.5 (5) Å30.22 × 0.21 × 0.18 mm
Z = 4

Data collection

Rigaku Saturn CCD area-detector diffractometer3102 independent reflections
Radiation source: rotating anode2455 reflections with I > 2σ(I)
confocalRint = 0.037
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 2.4°
[var phi] and ω scansh = −9→15
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)k = −17→17
Tmin = 0.531, Tmax = 0.588l = −10→11
10637 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)] = 0.028Hydrogen site location: mixed
wR(F2) = 0.071H atoms treated by a mixture of independent and constrained refinement
S = 1.03w = 1/[σ2(Fo2) + (0.0398P)2] where P = (Fo2 + 2Fc2)/3
3102 reflections(Δ/σ)max = 0.001
178 parametersΔρmax = 0.38 e Å3
0 restraintsΔρmin = −0.66 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
Br10.542001 (19)0.267131 (17)1.09928 (3)0.01935 (8)
S10.23555 (5)0.35572 (4)0.64144 (6)0.01313 (13)
O10.27402 (13)0.33591 (11)0.50006 (17)0.0180 (3)
O20.14905 (13)0.29181 (11)0.67992 (18)0.0174 (3)
N10.34782 (16)0.34723 (14)0.8024 (2)0.0142 (4)
H10.339 (2)0.312 (2)0.861 (3)0.026 (8)*
N20.46548 (15)0.46217 (13)0.7147 (2)0.0143 (4)
C10.45737 (17)0.39383 (15)0.8237 (2)0.0118 (4)
C20.55266 (18)0.36978 (14)0.9520 (2)0.0119 (4)
C30.65784 (18)0.42026 (15)0.9708 (2)0.0146 (4)
H30.72290.40561.05980.018*
C40.66762 (18)0.49303 (15)0.8579 (2)0.0137 (4)
C50.56853 (19)0.50966 (15)0.7326 (2)0.0146 (4)
H50.57360.55800.65370.018*
C60.77966 (19)0.55118 (16)0.8732 (3)0.0194 (5)
H6A0.77560.58620.77190.029*
H6B0.84630.50470.89710.029*
H6C0.78980.60040.96040.029*
C70.18506 (18)0.48129 (15)0.6312 (2)0.0131 (4)
C80.09300 (18)0.50427 (16)0.6980 (2)0.0135 (4)
H80.05810.45340.74710.016*
C90.05321 (18)0.60313 (16)0.6914 (2)0.0158 (4)
H9−0.00990.61930.73560.019*
C100.10400 (19)0.67832 (15)0.6215 (2)0.0150 (4)
C110.19340 (19)0.65226 (16)0.5508 (3)0.0166 (5)
H110.22690.70270.49900.020*
C120.23404 (18)0.55464 (16)0.5549 (2)0.0154 (4)
H120.29470.53800.50610.018*
C130.0635 (2)0.78579 (17)0.6201 (3)0.0216 (5)
H13A0.12960.82830.67550.032*
H13B0.00120.79030.67530.032*
H13C0.03320.80860.50870.032*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Br10.01556 (13)0.02025 (13)0.02032 (14)−0.00270 (9)0.00147 (9)0.00962 (9)
S10.0115 (3)0.0124 (2)0.0134 (3)0.0010 (2)−0.0002 (2)−0.00113 (19)
O10.0207 (8)0.0192 (8)0.0133 (8)0.0031 (7)0.0029 (7)−0.0030 (6)
O20.0123 (8)0.0144 (7)0.0235 (9)−0.0028 (6)0.0011 (7)0.0003 (6)
N10.0114 (9)0.0164 (9)0.0135 (10)−0.0018 (8)0.0009 (8)0.0047 (8)
N20.0138 (9)0.0157 (9)0.0130 (8)0.0020 (7)0.0026 (7)0.0018 (7)
C10.0119 (10)0.0119 (10)0.0124 (10)0.0006 (8)0.0047 (8)−0.0027 (8)
C20.0144 (10)0.0104 (9)0.0119 (10)−0.0005 (8)0.0051 (8)−0.0003 (8)
C30.0130 (10)0.0157 (10)0.0128 (11)0.0001 (9)−0.0005 (9)−0.0014 (8)
C40.0156 (11)0.0120 (10)0.0139 (10)−0.0011 (9)0.0049 (9)−0.0005 (8)
C50.0187 (11)0.0115 (10)0.0148 (10)−0.0006 (9)0.0063 (9)0.0027 (8)
C60.0170 (12)0.0192 (11)0.0218 (12)−0.0034 (10)0.0051 (9)0.0039 (9)
C70.0121 (10)0.0133 (10)0.0115 (10)0.0018 (8)−0.0008 (8)0.0001 (8)
C80.0108 (10)0.0167 (10)0.0123 (10)−0.0011 (9)0.0019 (8)0.0001 (8)
C90.0117 (10)0.0215 (11)0.0140 (11)0.0019 (9)0.0031 (9)−0.0023 (9)
C100.0141 (11)0.0141 (11)0.0138 (11)0.0017 (9)−0.0015 (9)−0.0011 (8)
C110.0138 (11)0.0173 (11)0.0177 (11)−0.0007 (9)0.0026 (9)0.0025 (9)
C120.0120 (10)0.0201 (11)0.0141 (11)0.0013 (9)0.0036 (9)0.0008 (8)
C130.0206 (12)0.0172 (12)0.0242 (13)0.0015 (9)0.0009 (10)−0.0009 (9)

Geometric parameters (Å, °)

Br1—C21.8925 (19)C6—H6B0.9800
S1—O11.4357 (15)C6—H6C0.9800
S1—O21.4361 (15)C7—C121.388 (3)
S1—N11.649 (2)C7—C81.396 (3)
S1—C71.768 (2)C8—C91.393 (3)
N1—C11.404 (3)C8—H80.9500
N1—H10.72 (2)C9—C101.385 (3)
N2—C11.330 (2)C9—H90.9500
N2—C51.345 (3)C10—C111.399 (3)
C1—C21.389 (3)C10—C131.507 (3)
C2—C31.385 (3)C11—C121.382 (3)
C3—C41.400 (3)C11—H110.9500
C3—H30.9500C12—H120.9500
C4—C51.384 (3)C13—H13A0.9800
C4—C61.510 (3)C13—H13B0.9800
C5—H50.9500C13—H13C0.9800
C6—H6A0.9800
O1—S1—O2119.68 (9)C4—C6—H6C109.5
O1—S1—N1109.63 (9)H6A—C6—H6C109.5
O2—S1—N1103.19 (9)H6B—C6—H6C109.5
O1—S1—C7108.09 (9)C12—C7—C8120.86 (19)
O2—S1—C7108.59 (10)C12—C7—S1120.64 (16)
N1—S1—C7106.98 (9)C8—C7—S1118.48 (15)
C1—N1—S1125.99 (15)C9—C8—C7118.85 (19)
C1—N1—H1120 (2)C9—C8—H8120.6
S1—N1—H1113 (2)C7—C8—H8120.6
C1—N2—C5118.33 (18)C10—C9—C8121.23 (19)
N2—C1—C2121.59 (19)C10—C9—H9119.4
N2—C1—N1116.62 (18)C8—C9—H9119.4
C2—C1—N1121.79 (18)C9—C10—C11118.52 (19)
C3—C2—C1119.62 (18)C9—C10—C13120.96 (19)
C3—C2—Br1119.36 (15)C11—C10—C13120.53 (19)
C1—C2—Br1121.01 (15)C12—C11—C10121.4 (2)
C2—C3—C4119.51 (19)C12—C11—H11119.3
C2—C3—H3120.2C10—C11—H11119.3
C4—C3—H3120.2C11—C12—C7119.1 (2)
C5—C4—C3116.35 (19)C11—C12—H12120.5
C5—C4—C6121.78 (18)C7—C12—H12120.5
C3—C4—C6121.87 (19)C10—C13—H13A109.5
N2—C5—C4124.57 (19)C10—C13—H13B109.5
N2—C5—H5117.7H13A—C13—H13B109.5
C4—C5—H5117.7C10—C13—H13C109.5
C4—C6—H6A109.5H13A—C13—H13C109.5
C4—C6—H6B109.5H13B—C13—H13C109.5
H6A—C6—H6B109.5
O1—S1—N1—C149.3 (2)C6—C4—C5—N2−178.28 (18)
O2—S1—N1—C1177.92 (17)O1—S1—C7—C12−31.16 (19)
C7—S1—N1—C1−67.63 (19)O2—S1—C7—C12−162.43 (16)
C5—N2—C1—C2−1.2 (3)N1—S1—C7—C1286.82 (18)
C5—N2—C1—N1178.89 (17)O1—S1—C7—C8147.25 (15)
S1—N1—C1—N210.4 (3)O2—S1—C7—C815.98 (18)
S1—N1—C1—C2−169.47 (15)N1—S1—C7—C8−94.77 (17)
N2—C1—C2—C32.3 (3)C12—C7—C8—C9−2.0 (3)
N1—C1—C2—C3−177.83 (18)S1—C7—C8—C9179.57 (15)
N2—C1—C2—Br1−176.47 (15)C7—C8—C9—C10−0.6 (3)
N1—C1—C2—Br13.4 (3)C8—C9—C10—C112.8 (3)
C1—C2—C3—C4−1.7 (3)C8—C9—C10—C13−177.77 (19)
Br1—C2—C3—C4177.10 (14)C9—C10—C11—C12−2.4 (3)
C2—C3—C4—C50.1 (3)C13—C10—C11—C12178.16 (19)
C2—C3—C4—C6179.38 (19)C10—C11—C12—C7−0.2 (3)
C1—N2—C5—C4−0.4 (3)C8—C7—C12—C112.4 (3)
C3—C4—C5—N21.0 (3)S1—C7—C12—C11−179.22 (16)

Hydrogen-bond geometry (Å, °)

Cg2 is is the centroid of the N2, C1–C5 ring.
D—H···AD—HH···AD···AD—H···A
N1—H1···Br10.72 (3)2.78 (2)3.134 (2)114 (2)
N1—H1···O1i0.72 (3)2.53 (3)3.225 (2)164 (3)
C3—H3···Cg1ii0.952.763.648 (2)155

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: RZ2394).

References

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  • Gabe, E. J. & White, P. S. (1993). DIFRAC American Crystallographic Association Meeting, Pittsburgh, Abstract PA 104.
  • Jackson, S. P., Schoenwaelder, S. M., Goncalves, I., Nesbitt, W. S., Yap, C. L., Wright, C. E., Kenche, V., Anderson, K. E., Dopheide, S. M., Yuan, Y., Sturgeon, S. A., Prabaharan, H., Thompson P. E., Smith, G. D., Shepherd, P. R., Daniele, N., Kulkarni, S., Abbott, B., Saylik, D., Jones, C., Lu, L., Giuliano, S., Hughan, S. C., Angus, J. A., Robertson, A. D. & Salem, H. H. (2005). Nat. Med.11, 507–514. [PubMed]
  • Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst.39, 453–457.
  • Rigaku/MSC (2005). CrystalClear Rigaku/MSC, The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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