N-(2-Bromo-4-methyl­phen­yl)-2-(5-methyl-2-phenyl­pyrazolo­[1,5-a]pyrimidin-7-yl)acetamide

Ibtissam Bassoude; Sabine Berteina-Raboin; El Mokhtar Essassi; Gérald Guillaumet; Lahcen El Ammari

doi:10.1107/S1600536813011811

. 2013 May 4;69(Pt 6):o829. doi: 10.1107/S1600536813011811

N-(2-Bromo-4-methylphenyl)-2-(5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-yl)acetamide

Ibtissam Bassoude ^a,^b,^*, Sabine Berteina-Raboin ^b, El Mokhtar Essassi ^a,^c, Gérald Guillaumet ^b, Lahcen El Ammari ^d

PMCID: PMC3684917 PMID: 23795019

Abstract

The fused pyrazole and pyrimidine rings in the title compound, C₂₂H₁₉BrN₄O, are almost coplanar, their planes being inclined to one another by 2.08 (13)°. The dihedral angles formed by the mean plane of the fused ring system and the phenyl and benzene rings are 16.21 (4) and 82.84 (4)°, respectively. An intramolecular N—H⋯N hydrogen bond is observed. In the crystal, molecules form inversion dimers via pairs of C—H⋯O hydrogen bonds. π–π interactions, with centroid–centroid distances of 3.4916 (9) Å, connect the dimers into a three-dimensional network.

Related literature

For pharmacological and biochemical properties of pyrazolo[1,5-a]pyrimidine derivatives, see: Selleri et al. (2005 ▶); Almansa et al. (2001 ▶); Suzuki et al. (2001 ▶); Chen et al. (2004 ▶). For related structures, see: Bassoude et al. (2013a ▶,b ▶). graphic file with name e-69-0o829-scheme1.jpg

Experimental

Crystal data

C₂₂H₁₉BrN₄O
M _r = 435.32
Monoclinic,
a = 9.8102 (6) Å
b = 7.2915 (4) Å
c = 27.0162 (14) Å
β = 92.942 (3)°
V = 1929.95 (19) Å³
Z = 4
Mo Kα radiation
μ = 2.15 mm⁻¹
T = 296 K
0.42 × 0.33 × 0.25 mm

Data collection

Bruker X8 APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.739, T _max = 0.867
29996 measured reflections
6371 independent reflections
3830 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.107
S = 1.02
6371 reflections
253 parameters
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.62 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; 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 ▶).

Supplementary Material

Click here for additional data file.^{(25.6KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813011811/rz5060sup1.cif

e-69-0o829-sup1.cif^{(25.6KB, cif)}

Click here for additional data file.^{(311.9KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813011811/rz5060Isup2.hkl

e-69-0o829-Isup2.hkl^{(311.9KB, hkl)}

Click here for additional data file.^{(7.4KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813011811/rz5060Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4A⋯N2	0.86	2.17	2.927 (2)	147
C14—H14⋯O1ⁱ	0.93	2.43	3.189 (2)	139

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

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

supplementary crystallographic information

Comment

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 development of heterocycles with a bridgehead nitrogen atom such the title compound and related compounds recently published (Bassoude et al. 2013a, 2013b).

The crystal structure of the title compound is built up from two fused five (N2/N3/C3–C5) and six-membered (N1/N3/C1–C3/C6) rings linked to one phenyl ring (C17–C22) and to a 2-bromo-4-methylphenyl ring (Br1/C9–C14) through an acetamide group as shown in Fig. 1. The pyrazole and pyrimidine rings are essentially planar with the maximum deviation of 0.0039 (15) and 0.0076 (15) Å for atom C3. The plane through the fused ring system makes a dihedral angles of 16.21 (4)° and 82.84 (4)° with the phenyl ring and with the 2-bromo-4-methylphenyl ring, respectively.

In the crystal (Fig. 2) molecules form inversion dimers via pairs of C14—H14···O1 hydrogen bonds. In addition, π–π interactions connect the dimers into a three-dimensional network, with centroid–centroid distances of 3.4916 (9) Å. An intramolecular N4—H4A···N2 hydrogen bond my help to define the conformation of the molecule.

Experimental

To a solution of 2-bromo-4-methylaniline (0.1 ml, 0.78 mmol) in 4 ml dichloromethane, under argon and at 273 K, were added 0.8 ml of trimethylaluminium in toluene (2M, 1.6 mmol), then the mixture was stirred for 15 min followed by addition of 0.2 g (0.68 mmol) of 7-ethoxycarbonyl-methyl-5-methylpyrazolo[1,5-a]pyrimidine. The reaction mixture was stirred to room temperature for 30 min then heated to reflux for 5 h. After evaporation of solvent under reduced pressure, the residue was extracted with CH₂Cl₂ and washed with a saturated NaCl solution. The combined organic layers were dried with MgSO₄ and concentrated under vacuum. The residue was purified on silica gel by column chromatography using mixture of petroleum ether and ethyl acetate (9:1 v/v) as eluent. The compound was recrystallized from a mixture of cyclohexane/ diethyl ether (1:1 v/v) to give colourless crystals.