Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Previous article
Next article
Previous article
Issue contents
Download PDF of article
Download CIF
3D view
Navigation
Highlighting
Dictionary of Crystallography reference
IUPAC Gold Book reference
more ...
Download citation
FormatBIBTeX
EndNote
RefMan
Refer
Medline
CIF
SGML
Plain Text
share
Next article

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 69| Part 5| May 2013| Page o749
https://doi.org/10.1107/S1600536813009896

7-Chloro-5-methyl-2-phenyl­pyrazolo­[1,5-a]pyrimidine

Ibtissam Bassoude,a,b* Sabine Berteina-Raboin,b El Mokhtar Essassi,a,c Gérald Guillaumetb and Lahcen El Ammarid

aLaboratoire de Chimie Organique Hétérocyclique URAC21, Pôle de Compétences Pharmacochimie, Université Mohammed V-Agdal, Avenue Ibn Battouta, BP 1014, Rabat, Morocco, bInstitut de Chimie Organique et Analytique, Université d'Orléans, UMR CNRS 6005, BP 6759, 45067 Orléans Cedex 2, France, cInstitute of Nanmaterials and Nanotechnology, MASCIR, Rabat, Morocco, and dLaboratoire de Chimie du Solide Appliquée, Université Mohammed V-Agdal, Faculté des Sciences, Avenue Ibn Battouta, BP 1014, Rabat, Morocco
*Correspondence e-mail: i_bassoude@yahoo.fr

(Received 3 April 2013; accepted 10 April 2013; online 17 April 2013)

The fused pyrazole and pyrimidine rings in the title compound, C13H10ClN3, are almost coplanar, their planes being inclined to one another by 0.8 (2)°. The mean plane of the fused ring system is nearly coplanar with the phenyl ring, as indicated by the dihedral angle between their planes of 9.06 (7)°.

Related literature

For pharmacological and biochemical properties of pyra­zolo­[1,5-a]pyrimidine derivatives, see: Selleri et al. (2005[Selleri, S., Gratteri, P., Costagli, C., Bonaccini, C., Costanzo, A., Melani, F., Guerrini, G., Ciciani, G., Costa, B., Spinetti, F., Martini, C. & Bruni, F. (2005). Bioorg. Med. Chem. 13, 4821-4834.]); Almansa et al. (2001[Almansa, C. A., Alberto, F., Cavalcanti, F. L., Gomez, L. A., Miralles, A., Merlos, M., Garcia-Rafanell, J. & Forn, J. (2001). J. Med. Chem. 44, 350-361.]); Suzuki et al. (2001[Suzuki, M., Iwasaki, H., Fujikawa, Y., Sakashita, M., Kitahara, M. & Sakoda, R. (2001). Bioorg. Med. Chem. Lett. 11, 1285-1288.]), Chen et al. (2004[Chen, C., Wilcoxen, K. M., Huang, C. Q., Xie, Y.-F., McCarthy, J. R., Webb, T. R., Zhu, Y.-F., Saunders, J., Liu, X.-J., Chen, T.-K., Bozigian, H. & Grigoriadis, D. E. (2004). J. Med. Chem. 47, 4787-4798.]). For related structures, see: Senga et al. (1981[Senga, K., Navinson, T. & Wilson, H. R. (1981). J. Med. Chem. 24, 610-613.]).

[Scheme 1]

Experimental

Crystal data

  • C13H10ClN3

  • Mr = 243.69

  • Monoclinic, P 21 /n

  • a = 6.5993 (2) Å

  • b = 12.6166 (4) Å

  • c = 13.8702 (5) Å

  • β = 100.131 (2)°

  • V = 1136.84 (6) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.31 mm−1

  • T = 296 K

  • 0.41 × 0.32 × 0.21 mm
Data collection

  • Bruker X8 APEXII area-detector diffractometer

  • 16957 measured reflections

  • 2925 independent reflections

  • 2521 reflections with I > 2σ(I)

  • Rint = 0.024
Refinement

  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 0.103

  • S = 1.06

  • 2925 reflections

  • 154 parameters

  • H-atom parameters constrained

  • Δρmax = 0.23 e Å−3

  • Δρmin = −0.23 e Å−3

Data collection: APEX2 (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]); software used to prepare material for publication: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536813009896/rz5056sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536813009896/rz5056Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536813009896/rz5056Isup3.cml

checkCIF report


Comment top

Pyrazolo[1,5-a]pyrimidines have attracted considerable interest because of their biological activity. For instance, they are known for their potent utility as selective peripheral benzodiazepine receptor ligands (Selleri et al., 2005), COX-2 selective inhibitors (Almansa et al., 2001), HMG-CoA reductase inhibitors (Suzuki et al., 2001) and CRF1 antagonists (Chen et al., 2004). Our research group targeted at the synthesis of heterocycles with a bridgehead nitrogen atom such as the title compound (Senga et al. 1981).

The crystal structure of the title compound is built up from two fused five and six-membered rings (N1/N2/C4–C6 and N1/N3/C1–C4) linked to a methyl group and to a phenyl ring (C7–C12) as shown in Fig. 1. The pyrazole and pyrimidine rings are essentially planar with maximum deviations of 0.0010 (13) Å and 0.0052 (13) Å for C6 and C1, respectively, and form a dihedral angle of 0.8 (2)°. The mean plane through the fused ring system makes a dihedral angle of 9.06 (7)° with the phenyl ring.

Related literature top

For pharmacological and biochemical properties of pyrazolo[1,5-a]pyrimidines derivatives, see: Selleri et al. (2005); Almansa et al. (2001); Suzuki et al. (2001), Chen et al. (2004). For related structures, see: Senga et al. (1981).

Experimental top

Under argon, a mixture of 7-hydroxy-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine (0.8 g, 3.5 mmol), phosphorus oxychloride (0.8 ml, 8.89 mmol) and triethylamine (1 mL, 7 mmol) in 1,4-dioxane (2 ml) was heated to reflux for 3 h. The reaction mixture was allowed to cool to room temperature. After evaporation of the solvent under reduced pressure and addition of a NaHCO3 saturated solution at 273 K (pH = 8), the residue was extracted with CH2Cl2. The combined organic layers were dried with MgSO4, concentrated under vacuum and the residue was purified on silica gel by column chromatography using a 9:1 (v/v) mixture of petroleum ether and ethyl acetate as eluent. The compound was recrystallized from a mixture of cyclohexane/CH2Cl2 (1:1 v/v) to give colourless crystals.

Refinement top

All H atoms could be located in a difference Fourier map and treated as riding with C—H = 0.93 Å (aromatic), and C—H = 0.96 Å (methyl) and with Uiso(H) = 1.2 Ueq(aromatic) or Uiso(H) = 1.5 Ueq (methyl).

Structure description top

Pyrazolo[1,5-a]pyrimidines have attracted considerable interest because of their biological activity. For instance, they are known for their potent utility as selective peripheral benzodiazepine receptor ligands (Selleri et al., 2005), COX-2 selective inhibitors (Almansa et al., 2001), HMG-CoA reductase inhibitors (Suzuki et al., 2001) and CRF1 antagonists (Chen et al., 2004). Our research group targeted at the synthesis of heterocycles with a bridgehead nitrogen atom such as the title compound (Senga et al. 1981).

The crystal structure of the title compound is built up from two fused five and six-membered rings (N1/N2/C4–C6 and N1/N3/C1–C4) linked to a methyl group and to a phenyl ring (C7–C12) as shown in Fig. 1. The pyrazole and pyrimidine rings are essentially planar with maximum deviations of 0.0010 (13) Å and 0.0052 (13) Å for C6 and C1, respectively, and form a dihedral angle of 0.8 (2)°. The mean plane through the fused ring system makes a dihedral angle of 9.06 (7)° with the phenyl ring.

For pharmacological and biochemical properties of pyrazolo[1,5-a]pyrimidines derivatives, see: Selleri et al. (2005); Almansa et al. (2001); Suzuki et al. (2001), Chen et al. (2004). For related structures, see: Senga et al. (1981).

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are represented as small circles of arbitrary radius.
7-Chloro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine top
Crystal data top
C13H10ClN3F(000) = 504
Mr = 243.69Dx = 1.418 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 2925 reflections
a = 6.5993 (2) Åθ = 3.0–28.7°
b = 12.6166 (4) ŵ = 0.31 mm−1
c = 13.8702 (5) ÅT = 296 K
β = 100.131 (2)°Block, colourless
V = 1136.84 (6) Å30.41 × 0.32 × 0.21 mm
Z = 4
Data collection top
Bruker X8 APEXII area-detector
diffractometer		2521 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.024
Graphite monochromatorθmax = 28.7°, θmin = 3.0°
φ and ω scansh = −6→8
16957 measured reflectionsk = −17→17
2925 independent reflectionsl = −18→18
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)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.103H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0523P)2 + 0.2738P]
where P = (Fo2 + 2Fc2)/3
2925 reflections(Δ/σ)max = 0.001
154 parametersΔρmax = 0.23 e Å−3
0 restraintsΔρmin = −0.23 e Å−3
Crystal data top
C13H10ClN3V = 1136.84 (6) Å3
Mr = 243.69Z = 4
Monoclinic, P21/nMo Kα radiation
a = 6.5993 (2) ŵ = 0.31 mm−1
b = 12.6166 (4) ÅT = 296 K
c = 13.8702 (5) Å0.41 × 0.32 × 0.21 mm
β = 100.131 (2)°
Data collection top
Bruker X8 APEXII area-detector
diffractometer		2521 reflections with I > 2σ(I)
16957 measured reflectionsRint = 0.024
2925 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.103H-atom parameters constrained
S = 1.06Δρmax = 0.23 e Å−3
2925 reflectionsΔρmin = −0.23 e Å−3
154 parameters
Special details top

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
C10.07651 (19)0.69856 (10)0.25074 (9)0.0344 (3)
C2−0.0283 (2)0.72024 (10)0.32394 (10)0.0393 (3)
H2−0.14590.76220.31210.047*
C30.0426 (2)0.67836 (11)0.41889 (10)0.0420 (3)
C40.3143 (2)0.59912 (10)0.36620 (9)0.0369 (3)
C50.4894 (2)0.54075 (11)0.36126 (9)0.0398 (3)
H50.57080.50410.41200.048*
C60.51851 (19)0.54836 (10)0.26417 (9)0.0349 (3)
C70.68242 (19)0.49912 (10)0.21982 (9)0.0353 (3)
C80.8475 (2)0.44870 (11)0.27861 (11)0.0423 (3)
H80.85460.44680.34620.051*
C91.0010 (2)0.40136 (12)0.23699 (13)0.0502 (4)
H91.11120.36840.27680.060*
C100.9911 (2)0.40282 (13)0.13685 (13)0.0522 (4)
H101.09400.37060.10920.063*
C110.8287 (2)0.45210 (13)0.07785 (12)0.0521 (4)
H110.82150.45280.01030.063*
C120.6755 (2)0.50072 (12)0.11910 (11)0.0448 (3)
H120.56710.53470.07890.054*
C13−0.0778 (3)0.69939 (16)0.49944 (12)0.0599 (4)
H13A−0.19460.74300.47480.090*
H13B0.00840.73520.55250.090*
H13C−0.12390.63340.52240.090*
N10.24981 (16)0.63830 (8)0.27118 (7)0.0332 (2)
N20.37353 (16)0.60790 (9)0.20808 (8)0.0357 (2)
N30.20986 (19)0.61941 (10)0.43971 (8)0.0432 (3)
Cl10.00409 (5)0.74223 (3)0.13336 (2)0.04662 (13)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0348 (6)0.0302 (5)0.0367 (6)0.0020 (5)0.0021 (5)0.0041 (5)
C20.0389 (7)0.0361 (6)0.0427 (7)0.0089 (5)0.0061 (5)0.0022 (5)
C30.0462 (7)0.0413 (7)0.0385 (6)0.0091 (6)0.0078 (5)−0.0005 (5)
C40.0393 (6)0.0370 (6)0.0326 (6)0.0047 (5)0.0014 (5)0.0011 (5)
C50.0401 (7)0.0423 (7)0.0351 (6)0.0103 (5)0.0012 (5)0.0014 (5)
C60.0331 (6)0.0323 (6)0.0382 (6)0.0011 (5)0.0029 (5)−0.0004 (5)
C70.0318 (6)0.0319 (6)0.0421 (6)−0.0016 (5)0.0061 (5)−0.0006 (5)
C80.0379 (7)0.0412 (7)0.0459 (7)0.0033 (5)0.0021 (5)−0.0029 (5)
C90.0359 (7)0.0483 (8)0.0647 (10)0.0074 (6)0.0044 (6)−0.0021 (7)
C100.0412 (8)0.0508 (8)0.0691 (10)0.0031 (6)0.0219 (7)−0.0026 (7)
C110.0527 (8)0.0576 (9)0.0508 (8)0.0019 (7)0.0224 (7)0.0033 (7)
C120.0414 (7)0.0502 (8)0.0436 (7)0.0053 (6)0.0095 (6)0.0043 (6)
C130.0659 (10)0.0735 (11)0.0433 (8)0.0281 (9)0.0176 (7)0.0038 (7)
N10.0334 (5)0.0318 (5)0.0338 (5)0.0036 (4)0.0042 (4)0.0023 (4)
N20.0344 (5)0.0360 (5)0.0368 (5)0.0026 (4)0.0068 (4)0.0024 (4)
N30.0479 (6)0.0474 (6)0.0335 (5)0.0130 (5)0.0053 (5)0.0004 (5)
Cl10.0463 (2)0.0521 (2)0.04017 (19)0.00949 (14)0.00399 (14)0.01307 (13)
Geometric parameters (Å, º) top
C1—C21.3533 (18)C7—C81.3940 (18)
C1—N11.3610 (16)C8—C91.386 (2)
C1—Cl11.7055 (13)C8—H80.9300
C2—C31.4197 (19)C9—C101.379 (2)
C2—H20.9300C9—H90.9300
C3—N31.3201 (18)C10—C111.377 (2)
C3—C131.504 (2)C10—H100.9300
C4—N31.3519 (17)C11—C121.389 (2)
C4—C51.3818 (18)C11—H110.9300
C4—N11.4019 (16)C12—H120.9300
C5—C61.3966 (18)C13—H13A0.9600
C5—H50.9300C13—H13B0.9600
C6—N21.3503 (16)C13—H13C0.9600
C6—C71.4727 (17)N1—N21.3532 (15)
C7—C121.3897 (19)
C2—C1—N1118.58 (11)C10—C9—C8120.34 (14)
C2—C1—Cl1123.81 (10)C10—C9—H9119.8
N1—C1—Cl1117.61 (9)C8—C9—H9119.8
C1—C2—C3119.48 (12)C11—C10—C9119.88 (14)
C1—C2—H2120.3C11—C10—H10120.1
C3—C2—H2120.3C9—C10—H10120.1
N3—C3—C2122.62 (12)C10—C11—C12120.10 (15)
N3—C3—C13117.87 (12)C10—C11—H11119.9
C2—C3—C13119.50 (13)C12—C11—H11119.9
N3—C4—C5132.85 (12)C11—C12—C7120.65 (14)
N3—C4—N1122.10 (11)C11—C12—H12119.7
C5—C4—N1105.05 (11)C7—C12—H12119.7
C4—C5—C6105.62 (11)C3—C13—H13A109.5
C4—C5—H5127.2C3—C13—H13B109.5
C6—C5—H5127.2H13A—C13—H13B109.5
N2—C6—C5112.96 (11)C3—C13—H13C109.5
N2—C6—C7119.48 (11)H13A—C13—H13C109.5
C5—C6—C7127.56 (11)H13B—C13—H13C109.5
C12—C7—C8118.62 (12)N2—N1—C1127.17 (10)
C12—C7—C6121.13 (12)N2—N1—C4112.96 (10)
C8—C7—C6120.25 (12)C1—N1—C4119.86 (11)
C9—C8—C7120.39 (14)C6—N2—N1103.41 (10)
C9—C8—H8119.8C3—N3—C4117.35 (11)
C7—C8—H8119.8

Experimental details

Crystal data
Chemical formulaC13H10ClN3
Mr243.69
Crystal system, space groupMonoclinic, P21/n
Temperature (K)296
a, b, c (Å)6.5993 (2), 12.6166 (4), 13.8702 (5)
β (°) 100.131 (2)
V (Å3)1136.84 (6)
Z4
Radiation typeMo Kα
µ (mm−1)0.31
Crystal size (mm)0.41 × 0.32 × 0.21
Data collection
DiffractometerBruker X8 APEXII area-detector
Absorption correction–
No. of measured, independent and
observed [I > 2σ(I)] reflections		16957, 2925, 2521
Rint0.024
(sin θ/λ)max (Å−1)0.675
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.103, 1.06
No. of reflections2925
No. of parameters154
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.23, −0.23

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

 

Acknowledgements

The authors thank the Unit of Support for Technical and Scientific Research (UATRS and CNRST) for the X-ray measurements.

References

First citationAlmansa, C. A., Alberto, F., Cavalcanti, F. L., Gomez, L. A., Miralles, A., Merlos, M., Garcia-Rafanell, J. & Forn, J. (2001). J. Med. Chem. 44, 350–361.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationBruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationChen, C., Wilcoxen, K. M., Huang, C. Q., Xie, Y.-F., McCarthy, J. R., Webb, T. R., Zhu, Y.-F., Saunders, J., Liu, X.-J., Chen, T.-K., Bozigian, H. & Grigoriadis, D. E. (2004). J. Med. Chem. 47, 4787–4798.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSelleri, S., Gratteri, P., Costagli, C., Bonaccini, C., Costanzo, A., Melani, F., Guerrini, G., Ciciani, G., Costa, B., Spinetti, F., Martini, C. & Bruni, F. (2005). Bioorg. Med. Chem. 13, 4821–4834.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationSenga, K., Navinson, T. & Wilson, H. R. (1981). J. Med. Chem. 24, 610–613.  CrossRef CAS PubMed Web of Science Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSuzuki, M., Iwasaki, H., Fujikawa, Y., Sakashita, M., Kitahara, M. & Sakoda, R. (2001). Bioorg. Med. Chem. Lett. 11, 1285–1288.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 69| Part 5| May 2013| Page o749
https://doi.org/10.1107/S1600536813009896
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS