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

Xu, J.; Liu, H.; Li, G.; Qi, C.

doi:10.1107/S160053681201166X

organic compounds

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ISSN: 2056-9890

Volume 68| Part 4| April 2012| Page o1161

doi:10.1107/S160053681201166X

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

Jingli Xu,^a Hang Liu,^a Guixia Li ^a and Chuanmin Qi ^a ^*

^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 ). 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

Crystal data

C₈H₄Cl₂N₄
M_r = 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 ) T_min = 0.693, T_max = 0.879
5429 measured reflections
2111 independent reflections
1749 reflections with I > 2σ(I)
R_int = 0.017

Refinement

R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.104
S = 1.04
2111 reflections
127 parameters
H-atom parameters constrained
Δρ_max = 0.46 e Å⁻³
Δρ_min = −0.53 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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 ); cell refinement: SAINT (Bruker, 1998 ); data reduction: SAINT; 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053681201166X/im2361sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681201166X/im2361Isup2.hkl

Supporting information file. DOI: 10.1107/S160053681201166X/im2361Isup3.cml

checkCIF report

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.

Structure description 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).

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

	Fig. 1. Molecular structure of the title compound showing displacement ellipsoids at the 45% probability level.
	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

C₈H₄Cl₂N₄	F(000) = 456
M_r = 227.05	D_x = 1.629 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2237 reflections
a = 4.9817 (4) Å	θ = 3.9–27.6°
b = 18.4025 (15) Å	µ = 0.66 mm⁻¹
c = 10.1526 (9) Å	T = 301 K
β = 95.924 (1)°	Block, red
V = 925.78 (13) Å³	0.60 × 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 tube	1749 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.017
phi and ω scans	θ_max = 27.6°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2007)	h = −6→6
T_min = 0.693, T_max = 0.879	k = −13→23
5429 measured reflections	l = −12→12

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.104	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.050P)² + 0.3703P] where P = (F_o² + 2F_c²)/3
2111 reflections	(Δ/σ)_max < 0.001
127 parameters	Δρ_max = 0.46 e Å⁻³
0 restraints	Δρ_min = −0.53 e Å⁻³

Crystal data top

C₈H₄Cl₂N₄	V = 925.78 (13) Å³
M_r = 227.05	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 4.9817 (4) Å	µ = 0.66 mm⁻¹
b = 18.4025 (15) Å	T = 301 K
c = 10.1526 (9) Å	0.60 × 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)
T_min = 0.693, T_max = 0.879	R_int = 0.017
5429 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	0 restraints
wR(F²) = 0.104	H-atom parameters constrained
S = 1.04	Δρ_max = 0.46 e Å⁻³
2111 reflections	Δρ_min = −0.53 e Å⁻³
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

	x	y	z	U_iso*/U_eq
Cl1	0.32935 (9)	0.26419 (3)	0.40816 (5)	0.04533 (17)
Cl2	0.73176 (14)	0.03358 (3)	0.13931 (8)	0.0784 (3)
N1	0.9223 (3)	0.23861 (8)	0.10690 (15)	0.0376 (3)
N2	1.2065 (4)	0.41634 (10)	−0.0585 (2)	0.0636 (5)
N3	0.5932 (4)	0.38077 (9)	0.26671 (18)	0.0503 (4)
N4	0.6551 (3)	0.31043 (8)	0.24035 (15)	0.0374 (3)
C1	0.5553 (4)	0.25052 (10)	0.29599 (18)	0.0363 (4)
C2	0.6391 (4)	0.18420 (10)	0.25839 (18)	0.0390 (4)
H2	0.5762	0.1420	0.2952	0.047*
C3	0.8249 (4)	0.18073 (10)	0.16175 (18)	0.0378 (4)
C4	0.9331 (5)	0.10975 (11)	0.1153 (2)	0.0554 (6)
H4A	1.1109	0.1018	0.1615	0.066*
H4B	0.9540	0.1138	0.0216	0.066*
C5	0.8380 (3)	0.30370 (10)	0.14617 (17)	0.0352 (4)
C6	0.8930 (4)	0.37484 (10)	0.11144 (19)	0.0423 (4)
C7	1.0677 (4)	0.39787 (10)	0.0175 (2)	0.0473 (5)
C8	0.7377 (5)	0.41835 (11)	0.1879 (2)	0.0520 (5)
H8	0.7362	0.4688	0.1837	0.062*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0409 (3)	0.0559 (3)	0.0418 (3)	−0.0012 (2)	0.01678 (19)	−0.0018 (2)
Cl2	0.0764 (4)	0.0456 (3)	0.1169 (6)	−0.0135 (3)	0.0270 (4)	−0.0184 (3)
N1	0.0376 (8)	0.0389 (8)	0.0378 (8)	0.0000 (6)	0.0108 (6)	0.0019 (6)
N2	0.0747 (13)	0.0502 (11)	0.0710 (13)	−0.0039 (10)	0.0321 (11)	0.0098 (10)
N3	0.0591 (11)	0.0374 (9)	0.0574 (10)	0.0019 (8)	0.0213 (8)	−0.0043 (8)
N4	0.0381 (8)	0.0379 (8)	0.0377 (8)	−0.0003 (6)	0.0110 (6)	−0.0009 (6)
C1	0.0323 (8)	0.0449 (10)	0.0328 (8)	−0.0023 (7)	0.0089 (7)	0.0012 (7)
C2	0.0403 (9)	0.0381 (10)	0.0398 (9)	−0.0032 (8)	0.0099 (8)	0.0035 (8)
C3	0.0403 (9)	0.0364 (9)	0.0376 (9)	−0.0009 (7)	0.0075 (7)	0.0007 (7)
C4	0.0654 (14)	0.0379 (11)	0.0676 (14)	0.0002 (10)	0.0292 (11)	−0.0003 (10)
C5	0.0333 (8)	0.0391 (9)	0.0341 (9)	−0.0023 (7)	0.0078 (7)	0.0007 (7)
C6	0.0458 (10)	0.0368 (10)	0.0458 (10)	−0.0045 (8)	0.0114 (8)	0.0033 (8)
C7	0.0549 (12)	0.0360 (10)	0.0527 (12)	−0.0045 (9)	0.0137 (10)	0.0047 (9)
C8	0.0621 (13)	0.0350 (10)	0.0612 (13)	−0.0022 (9)	0.0177 (11)	−0.0011 (9)

Geometric parameters (Å, º) top

Cl1—C1	1.7006 (18)	C2—C3	1.418 (2)
Cl2—C4	1.755 (2)	C2—H2	0.9300
N1—C3	1.318 (2)	C3—C4	1.507 (3)
N1—C5	1.343 (2)	C4—H4A	0.9700
N2—C7	1.139 (3)	C4—H4B	0.9700
N3—C8	1.325 (3)	C5—C6	1.390 (3)
N3—N4	1.364 (2)	C6—C8	1.402 (3)
N4—C1	1.356 (2)	C6—C7	1.421 (3)
N4—C5	1.393 (2)	C8—H8	0.9300
C1—C2	1.357 (3)

C3—N1—C5	117.09 (15)	C3—C4—H4A	108.6
C8—N3—N4	103.25 (16)	Cl2—C4—H4A	108.6
C1—N4—N3	126.15 (15)	C3—C4—H4B	108.6
C1—N4—C5	120.50 (15)	Cl2—C4—H4B	108.6
N3—N4—C5	113.35 (15)	H4A—C4—H4B	107.5
N4—C1—C2	118.49 (16)	N1—C5—C6	133.52 (16)
N4—C1—Cl1	117.07 (14)	N1—C5—N4	121.99 (15)
C2—C1—Cl1	124.44 (14)	C6—C5—N4	104.50 (15)
C1—C2—C3	118.48 (16)	C5—C6—C8	105.24 (17)
C1—C2—H2	120.8	C5—C6—C7	126.97 (18)
C3—C2—H2	120.8	C8—C6—C7	127.79 (19)
N1—C3—C2	123.45 (17)	N2—C7—C6	179.6 (3)
N1—C3—C4	114.14 (16)	N3—C8—C6	113.67 (19)
C2—C3—C4	122.40 (16)	N3—C8—H8	123.2
C3—C4—Cl2	114.86 (15)	C6—C8—H8	123.2

C8—N3—N4—C1	−179.43 (19)	C3—N1—C5—C6	−179.6 (2)
C8—N3—N4—C5	0.3 (2)	C3—N1—C5—N4	−0.2 (3)
N3—N4—C1—C2	−179.90 (18)	C1—N4—C5—N1	0.0 (3)
C5—N4—C1—C2	0.4 (3)	N3—N4—C5—N1	−179.71 (17)
N3—N4—C1—Cl1	0.6 (3)	C1—N4—C5—C6	179.58 (16)
C5—N4—C1—Cl1	−179.05 (13)	N3—N4—C5—C6	−0.1 (2)
N4—C1—C2—C3	−0.6 (3)	N1—C5—C6—C8	179.4 (2)
Cl1—C1—C2—C3	178.78 (14)	N4—C5—C6—C8	0.0 (2)
C5—N1—C3—C2	−0.1 (3)	N1—C5—C6—C7	0.0 (4)
C5—N1—C3—C4	−178.66 (18)	N4—C5—C6—C7	−179.5 (2)
C1—C2—C3—N1	0.5 (3)	N4—N3—C8—C6	−0.3 (3)
C1—C2—C3—C4	178.98 (19)	C5—C6—C8—N3	0.2 (3)
N1—C3—C4—Cl2	−159.03 (16)	C7—C6—C8—N3	179.7 (2)
C2—C3—C4—Cl2	22.4 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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+1/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₈H₄Cl₂N₄
M_r	227.05
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	301
a, b, c (Å)	4.9817 (4), 18.4025 (15), 10.1526 (9)
β (°)	95.924 (1)
V (Å³)	925.78 (13)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.66
Crystal size (mm)	0.60 × 0.48 × 0.20

Data collection
Diffractometer	Bruker SMART APEX CCD area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2007)
T_min, T_max	0.693, 0.879
No. of measured, independent and observed [I > 2σ(I)] reflections	5429, 2111, 1749
R_int	0.017
(sin θ/λ)_max (Å⁻¹)	0.652

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.104, 1.04
No. of reflections	2111
No. of parameters	127
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	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···A	D—H	H···A	D···A	D—H···A
C8—H8···N2ⁱ	0.93	2.50	3.337 (3)	150.2
C2—H2···N2ⁱⁱ	0.93	2.70	3.515 (3)	146.0

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

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