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

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

doi:10.1107/S1600536813009902

. 2013 Apr 17;69(Pt 5):o740. doi: 10.1107/S1600536813009902

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

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

PMCID: PMC3648271 PMID: 23723891

Abstract

The fused pyrazole and pyrimidine rings in the title compound, C₁₆H₁₅N₃O₂, are almost coplanar, being inclined to one another by 1.31 (12)°. The mean plane of this fused ring system is nearly coplanar with the phenyl ring, as indicated by the dihedral angle between their planes of 1.31 (12)°. The fused-ring system and the phenyl ring are nearly coplanar, as indicated by the dihedral angle of 1.27 (10)°. In the crystal, molecules form inversion dimers via pairs of C—H⋯O hydrogen bonds. C—H⋯N interactions connect the dimers into a three-dimensional network. In addition, π–π contacts are observed, with centroid–centroid distances of 3.426 (2) Å.

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: Chimichi et al. (1992 ▶). graphic file with name e-69-0o740-scheme1.jpg

Experimental

Crystal data

C₁₆H₁₅N₃O₂
M _r = 281.31
Orthorhombic,
a = 8.0542 (8) Å
b = 16.4104 (19) Å
c = 21.635 (2) Å
V = 2859.5 (5) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 296 K
0.41 × 0.32 × 0.21 mm

Data collection

Bruker X8 APEXII area-detector diffractometer
12894 measured reflections
2783 independent reflections
1919 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.052
wR(F ²) = 0.170
S = 1.04
2783 reflections
190 parameters
H-atom parameters constrained
Δρ_max = 0.35 e Å⁻³
Δρ_min = −0.36 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.^{(24.1KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813009902/rz5057sup1.cif

e-69-0o740-sup1.cif^{(24.1KB, cif)}

Click here for additional data file.^{(136.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813009902/rz5057Isup2.hkl

e-69-0o740-Isup2.hkl^{(136.7KB, hkl)}

Click here for additional data file.^{(5.7KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813009902/rz5057Isup3.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
C12—H12⋯O1ⁱ	0.93	2.36	3.258 (3)	161
C6—H6⋯N3ⁱⁱ	0.93	2.62	3.507 (3)	161

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

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

The condensation of 5-amino-3-arylpyrazoles with ethyl 2,4-dioxopentanoate leads to the title compound ethyl-7-methyl-2-phenylpyrazolo[1,5-a]pyrimidine- 5-carboxylate and its isomeric ethyl 5-methyl-2-phenylpyrazolo[1,5-a]pyrimidine-7-carboxylate (Chimichi et al., 1992).

The crystal structure of the title compound is built up from two fused five and six-membered rings (N1/N2/C2–C4 and N2/N3/C1/C2/C11/C12) linked to a methyl, a phenyl (C5–C10) and to an ethylcarboxylate group (C14/O1/O2/C15/C16) as shown in Fig. 1. The pyrazole and pyrimidine rings are almost planar with a maximum deviation for atom C6 of 0.002 (2) Å and 0.004 (2) Å, respectively. The mean plane through the two fused rings is slightly folded around the common edge as indicated by the dihedral angle between them of 1.31 (12)°. The dihedral angle between the phenyl ring and the fused-ring system is 1.27 (10)°.

In the crystal structure C12–H12···O1 hydrogen bonds form inversion dimers. Intermolecular C6—H6···N3 interactions connect the dimers into a three dimensional network. In addition, the molecules are connected by π–π contacts, with centroid–centroid distances of 3.426 (2) Å.

Experimental

A solution of ethyl 2,4-dioxopentanoate (1.64 g, 10.4 mmol) and 5-amino-3-phenylpyrazole (1.5 g, 9.4 mmol) in 10 ml of EtOH was heated to reflux for 30 min. After evaporation of solvent under reduced pressure, the residue was purified on silica gel by column chromatography using a 8:2 (v/v) mixture of petroleum ether and ethyl acetate as eluent. Ethyl-7-methyl-2-phenylpyrazolo[1,5-a]pyrimidine-5-carboxylate was recrystallized from cyclohexane to give colourless crystals.