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

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ISSN: 2056-9890

7-Chloro-5-(chloro­meth­yl)pyrazolo­[1,5-a]pyrimidine-3-carbo­nitrile

aKey Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Xin Jie Kou Wai Street 19, 100875 Beijing, People's Republic of China
*Correspondence e-mail: qicmin@sohu.com

(Received 23 February 2012; accepted 18 March 2012; online 24 March 2012)

All non-H atoms of the title compound, C8H4Cl2N4, are essentially coplanar, with an r.m.s. deviation of 0.011 Å. In the crystal, weak C—H⋯N hydrogen bonds link the mol­ecules into infinite sheets parallel to the bc plane.

Related literature

For details of the synthesis, see: Li et al. (2006[Li, J., Zhao, Y., Zhao, X., Yuan, X. & Gong, P. (2006). Arch. Pharm. Chem. Life Sci. 339, 593-597.]). For applications of pyrazolo­[1,5-a]pyrimidines as pharmacophores or building blocks in anti-tumor drug design, see: Li et al. (2006[Li, J., Zhao, Y., Zhao, X., Yuan, X. & Gong, P. (2006). Arch. Pharm. Chem. Life Sci. 339, 593-597.]); Di Grandi et al. (2009[Di Grandi, M. J., Berger, D. M., Hopper, D. W., Zhang, C., Dutia, M., Dunnick, A. L., Torres, N., Levin, J. I., Diamantidis, G., Zapf, C. W., Bloom, J. D., Dennis Powell, Y. B. H., Wojciechowicz, D., Collins, K. & Frommer, E. (2009). Bioorg. Med. Chem. Lett. 19, 6957-6961.]); Powell et al. (2007[Powell, D., Gopalsamy, A., Wang, Y. D., Zhang, N., Miranda, M., McGinnis, J. P. & Rabindran, S. K. (2007). Bioorg. Med. Chem. Lett. 17, 1641-1645.]); Gopalsamy et al. (2005[Gopalsamy, A., Yang, H., Ellingboe, J. W., Tsou, H.-R., Zhang, N., Honores, E., Powell, D., Miranda, M., McGinnisb, J. P. & Rabindranb, S. K. (2005). Bioorg. Med. Chem. Lett. 15, 1591-1594.]).

[Scheme 1]

Experimental

Crystal data
  • C8H4Cl2N4

  • Mr = 227.05

  • Monoclinic, P 21 /c

  • a = 4.9817 (4) Å

  • b = 18.4025 (15) Å

  • c = 10.1526 (9) Å

  • β = 95.924 (1)°

  • V = 925.78 (13) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.66 mm−1

  • T = 301 K

  • 0.60 × 0.48 × 0.20 mm

Data collection
  • Bruker SMART APEX CCD area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2007[Bruker (2007). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.693, Tmax = 0.879

  • 5429 measured reflections

  • 2111 independent reflections

  • 1749 reflections with I > 2σ(I)

  • Rint = 0.017

Refinement
  • R[F2 > 2σ(F2)] = 0.038

  • wR(F2) = 0.104

  • S = 1.04

  • 2111 reflections

  • 127 parameters

  • H-atom parameters constrained

  • Δρmax = 0.46 e Å−3

  • Δρmin = −0.53 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C8—H8⋯N2i 0.93 2.50 3.337 (3) 150
C2—H2⋯N2ii 0.93 2.70 3.515 (3) 146
Symmetry codes: (i) -x+2, -y+1, -z; (ii) [x-1, -y+{\script{1\over 2}}, z+{\script{1\over 2}}].

Data collection: SMART (Bruker, 1998[Bruker (1998). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 1998[Bruker (2005). SAINT. 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: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

Pyrazolo[1,5-a]pyrimidines are widely applied as important pharmacophores or building blocks in anti-tumor drug design (Di Grandi et al., 2009; Powell et al., 2007; Gopalsamy et al., 2005; Li et al., 2006). Thus, the synthesis of the title compound may lead to the development of further pyrazolo[1,5-a]pyrimidine derivatives as new anti-tumor drugs. Here we report the crystal structure of the title compound.

The molecular structure of the title compound is shown in Fig. 1. The complete molecule is essentially planar, except the H atoms of the methylene group. Each molecule acts as a donor and a acceptor of weak intermolecular C—H···N hydrogen-bond interactions linking the molecules into infinite sheets (Fig. 2).

Related literature top

For details of the synthesis, see: Li et al. (2006). For applications of pyrazolo[1,5-a]pyrimidines as pharmacophores or building blocks in anti-tumor drug design, see: Li et al. (2006); Di Grandi et al. (2009); Powell et al. (2007); Gopalsamy et al. (2005).

Experimental top

The title compound can prepared by the reaction of 5-(chloromethyl)-7-hydroxypyrazolo[1,5-a]pyrimidine-3-carbonitrile with phosphorus oxychloride (Li et al., 2006). Crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution of the crude product in ethyl acetate at ambient temperature.

Refinement top

All H atoms attached to C atoms were fixed geometrically and treated as riding with C—H = 0.93 Å (CH) and C—H = 0.97 Å (CH2) with Uiso(H) =1.2Ueq(C).

Structure description top

Pyrazolo[1,5-a]pyrimidines are widely applied as important pharmacophores or building blocks in anti-tumor drug design (Di Grandi et al., 2009; Powell et al., 2007; Gopalsamy et al., 2005; Li et al., 2006). Thus, the synthesis of the title compound may lead to the development of further pyrazolo[1,5-a]pyrimidine derivatives as new anti-tumor drugs. Here we report the crystal structure of the title compound.

The molecular structure of the title compound is shown in Fig. 1. The complete molecule is essentially planar, except the H atoms of the methylene group. Each molecule acts as a donor and a acceptor of weak intermolecular C—H···N hydrogen-bond interactions linking the molecules into infinite sheets (Fig. 2).

For details of the synthesis, see: Li et al. (2006). For applications of pyrazolo[1,5-a]pyrimidines as pharmacophores or building blocks in anti-tumor drug design, see: Li et al. (2006); Di Grandi et al. (2009); Powell et al. (2007); Gopalsamy et al. (2005).

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); 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: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound showing displacement ellipsoids at the 45% probability level.
[Figure 2] Fig. 2. Packing diagram of the title compound, viewed along the a axis. Dashed lines indicate hydrogen bonds.
7-Chloro-5-(chloromethyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile top
Crystal data top
C8H4Cl2N4F(000) = 456
Mr = 227.05Dx = 1.629 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2237 reflections
a = 4.9817 (4) Åθ = 3.9–27.6°
b = 18.4025 (15) ŵ = 0.66 mm1
c = 10.1526 (9) ÅT = 301 K
β = 95.924 (1)°Block, red
V = 925.78 (13) Å30.60 × 0.48 × 0.20 mm
Z = 4
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2111 independent reflections
Radiation source: fine-focus sealed tube1749 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.017
phi and ω scansθmax = 27.6°, θmin = 2.3°
Absorption correction: multi-scan
(SADABS; Bruker, 2007)
h = 66
Tmin = 0.693, Tmax = 0.879k = 1323
5429 measured reflectionsl = 1212
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)] = 0.038Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.104H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.050P)2 + 0.3703P]
where P = (Fo2 + 2Fc2)/3
2111 reflections(Δ/σ)max < 0.001
127 parametersΔρmax = 0.46 e Å3
0 restraintsΔρmin = 0.53 e Å3
Crystal data top
C8H4Cl2N4V = 925.78 (13) Å3
Mr = 227.05Z = 4
Monoclinic, P21/cMo Kα radiation
a = 4.9817 (4) ŵ = 0.66 mm1
b = 18.4025 (15) ÅT = 301 K
c = 10.1526 (9) Å0.60 × 0.48 × 0.20 mm
β = 95.924 (1)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2111 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2007)
1749 reflections with I > 2σ(I)
Tmin = 0.693, Tmax = 0.879Rint = 0.017
5429 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0380 restraints
wR(F2) = 0.104H-atom parameters constrained
S = 1.04Δρmax = 0.46 e Å3
2111 reflectionsΔρmin = 0.53 e Å3
127 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
Cl10.32935 (9)0.26419 (3)0.40816 (5)0.04533 (17)
Cl20.73176 (14)0.03358 (3)0.13931 (8)0.0784 (3)
N10.9223 (3)0.23861 (8)0.10690 (15)0.0376 (3)
N21.2065 (4)0.41634 (10)0.0585 (2)0.0636 (5)
N30.5932 (4)0.38077 (9)0.26671 (18)0.0503 (4)
N40.6551 (3)0.31043 (8)0.24035 (15)0.0374 (3)
C10.5553 (4)0.25052 (10)0.29599 (18)0.0363 (4)
C20.6391 (4)0.18420 (10)0.25839 (18)0.0390 (4)
H20.57620.14200.29520.047*
C30.8249 (4)0.18073 (10)0.16175 (18)0.0378 (4)
C40.9331 (5)0.10975 (11)0.1153 (2)0.0554 (6)
H4A1.11090.10180.16150.066*
H4B0.95400.11380.02160.066*
C50.8380 (3)0.30370 (10)0.14617 (17)0.0352 (4)
C60.8930 (4)0.37484 (10)0.11144 (19)0.0423 (4)
C71.0677 (4)0.39787 (10)0.0175 (2)0.0473 (5)
C80.7377 (5)0.41835 (11)0.1879 (2)0.0520 (5)
H80.73620.46880.18370.062*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0409 (3)0.0559 (3)0.0418 (3)0.0012 (2)0.01678 (19)0.0018 (2)
Cl20.0764 (4)0.0456 (3)0.1169 (6)0.0135 (3)0.0270 (4)0.0184 (3)
N10.0376 (8)0.0389 (8)0.0378 (8)0.0000 (6)0.0108 (6)0.0019 (6)
N20.0747 (13)0.0502 (11)0.0710 (13)0.0039 (10)0.0321 (11)0.0098 (10)
N30.0591 (11)0.0374 (9)0.0574 (10)0.0019 (8)0.0213 (8)0.0043 (8)
N40.0381 (8)0.0379 (8)0.0377 (8)0.0003 (6)0.0110 (6)0.0009 (6)
C10.0323 (8)0.0449 (10)0.0328 (8)0.0023 (7)0.0089 (7)0.0012 (7)
C20.0403 (9)0.0381 (10)0.0398 (9)0.0032 (8)0.0099 (8)0.0035 (8)
C30.0403 (9)0.0364 (9)0.0376 (9)0.0009 (7)0.0075 (7)0.0007 (7)
C40.0654 (14)0.0379 (11)0.0676 (14)0.0002 (10)0.0292 (11)0.0003 (10)
C50.0333 (8)0.0391 (9)0.0341 (9)0.0023 (7)0.0078 (7)0.0007 (7)
C60.0458 (10)0.0368 (10)0.0458 (10)0.0045 (8)0.0114 (8)0.0033 (8)
C70.0549 (12)0.0360 (10)0.0527 (12)0.0045 (9)0.0137 (10)0.0047 (9)
C80.0621 (13)0.0350 (10)0.0612 (13)0.0022 (9)0.0177 (11)0.0011 (9)
Geometric parameters (Å, º) top
Cl1—C11.7006 (18)C2—C31.418 (2)
Cl2—C41.755 (2)C2—H20.9300
N1—C31.318 (2)C3—C41.507 (3)
N1—C51.343 (2)C4—H4A0.9700
N2—C71.139 (3)C4—H4B0.9700
N3—C81.325 (3)C5—C61.390 (3)
N3—N41.364 (2)C6—C81.402 (3)
N4—C11.356 (2)C6—C71.421 (3)
N4—C51.393 (2)C8—H80.9300
C1—C21.357 (3)
C3—N1—C5117.09 (15)C3—C4—H4A108.6
C8—N3—N4103.25 (16)Cl2—C4—H4A108.6
C1—N4—N3126.15 (15)C3—C4—H4B108.6
C1—N4—C5120.50 (15)Cl2—C4—H4B108.6
N3—N4—C5113.35 (15)H4A—C4—H4B107.5
N4—C1—C2118.49 (16)N1—C5—C6133.52 (16)
N4—C1—Cl1117.07 (14)N1—C5—N4121.99 (15)
C2—C1—Cl1124.44 (14)C6—C5—N4104.50 (15)
C1—C2—C3118.48 (16)C5—C6—C8105.24 (17)
C1—C2—H2120.8C5—C6—C7126.97 (18)
C3—C2—H2120.8C8—C6—C7127.79 (19)
N1—C3—C2123.45 (17)N2—C7—C6179.6 (3)
N1—C3—C4114.14 (16)N3—C8—C6113.67 (19)
C2—C3—C4122.40 (16)N3—C8—H8123.2
C3—C4—Cl2114.86 (15)C6—C8—H8123.2
C8—N3—N4—C1179.43 (19)C3—N1—C5—C6179.6 (2)
C8—N3—N4—C50.3 (2)C3—N1—C5—N40.2 (3)
N3—N4—C1—C2179.90 (18)C1—N4—C5—N10.0 (3)
C5—N4—C1—C20.4 (3)N3—N4—C5—N1179.71 (17)
N3—N4—C1—Cl10.6 (3)C1—N4—C5—C6179.58 (16)
C5—N4—C1—Cl1179.05 (13)N3—N4—C5—C60.1 (2)
N4—C1—C2—C30.6 (3)N1—C5—C6—C8179.4 (2)
Cl1—C1—C2—C3178.78 (14)N4—C5—C6—C80.0 (2)
C5—N1—C3—C20.1 (3)N1—C5—C6—C70.0 (4)
C5—N1—C3—C4178.66 (18)N4—C5—C6—C7179.5 (2)
C1—C2—C3—N10.5 (3)N4—N3—C8—C60.3 (3)
C1—C2—C3—C4178.98 (19)C5—C6—C8—N30.2 (3)
N1—C3—C4—Cl2159.03 (16)C7—C6—C8—N3179.7 (2)
C2—C3—C4—Cl222.4 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C8—H8···N2i0.932.503.337 (3)150
C2—H2···N2ii0.932.703.515 (3)146
Symmetry codes: (i) x+2, y+1, z; (ii) x1, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC8H4Cl2N4
Mr227.05
Crystal system, space groupMonoclinic, P21/c
Temperature (K)301
a, b, c (Å)4.9817 (4), 18.4025 (15), 10.1526 (9)
β (°) 95.924 (1)
V3)925.78 (13)
Z4
Radiation typeMo Kα
µ (mm1)0.66
Crystal size (mm)0.60 × 0.48 × 0.20
Data collection
DiffractometerBruker SMART APEX CCD area-detector
Absorption correctionMulti-scan
(SADABS; Bruker, 2007)
Tmin, Tmax0.693, 0.879
No. of measured, independent and
observed [I > 2σ(I)] reflections
5429, 2111, 1749
Rint0.017
(sin θ/λ)max1)0.652
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.104, 1.04
No. of reflections2111
No. of parameters127
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.46, 0.53

Computer programs: SMART (Bruker, 1998), SAINT (Bruker, 1998), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C8—H8···N2i0.932.503.337 (3)150.2
C2—H2···N2ii0.932.703.515 (3)146.0
Symmetry codes: (i) x+2, y+1, z; (ii) x1, y+1/2, z+1/2.
 

Acknowledgements

This project was sponsored by the National Natural Science Foundation of China (No.21071022) and the Fundamental Research Funds for the Central Universities.

References

First citationBruker (1998). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBruker (2005). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBruker (2007). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationDi Grandi, M. J., Berger, D. M., Hopper, D. W., Zhang, C., Dutia, M., Dunnick, A. L., Torres, N., Levin, J. I., Diamantidis, G., Zapf, C. W., Bloom, J. D., Dennis Powell, Y. B. H., Wojciechowicz, D., Collins, K. & Frommer, E. (2009). Bioorg. Med. Chem. Lett. 19, 6957–6961.  Web of Science CrossRef PubMed CAS Google Scholar
First citationGopalsamy, A., Yang, H., Ellingboe, J. W., Tsou, H.-R., Zhang, N., Honores, E., Powell, D., Miranda, M., McGinnisb, J. P. & Rabindranb, S. K. (2005). Bioorg. Med. Chem. Lett. 15, 1591–1594.  Web of Science CrossRef PubMed CAS Google Scholar
First citationLi, J., Zhao, Y., Zhao, X., Yuan, X. & Gong, P. (2006). Arch. Pharm. Chem. Life Sci. 339, 593–597.  Web of Science CrossRef CAS Google Scholar
First citationPowell, D., Gopalsamy, A., Wang, Y. D., Zhang, N., Miranda, M., McGinnis, J. P. & Rabindran, S. K. (2007). Bioorg. Med. Chem. Lett. 17, 1641–1645.  Web of Science CrossRef PubMed CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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