supplementary materials


rz5057 scheme

Acta Cryst. (2013). E69, o740    [ doi:10.1107/S1600536813009902 ]

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

I. Bassoude, S. Berteina-Raboin, E. M. Essassi, G. Guillaumet and L. El Ammari

Abstract top

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, [pi]-[pi] contacts are observed, with centroid-centroid distances of 3.426 (2) Å.

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).

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 ππ contacts, with centroid–centroid distances of 3.426 (2) Å.

Related literature top

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).

Experimental top

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.

Refinement top

All H atoms could be located in a difference Fourier map and treated as riding with C—H = 0.93 Å (aromatic), C—H = 0.97 Å (methylene) and C—H = 0.96 Å (methyl), and with Uiso(H) = 1.2 Ueq(aromatic, methylene) or Uiso(H) = 1.5 Ueq (methyl).

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.
[Figure 2] Fig. 2. Crystal packing of the title compound showing C12–H12···O1 and C6–H6···N3 hydrogen bonds as blue dashed lines, with C—H···π interactions and a ππ contact (red lines). The red spheres represent the centroids of the C5–C10 and N2/N3/C1/C2/C11/C12 rings and their symmetry partners.
Ethyl 7-methyl-2-phenylpyrazolo[1,5-a]pyrimidine-5-carboxylate top
Crystal data top
C16H15N3O2F(000) = 1184
Mr = 281.31Dx = 1.307 Mg m3
Orthorhombic, PbcaMo Kα radiation, λ = 0.71073 Å
Hall symbol: -p 2ac 2abCell parameters from 2783 reflections
a = 8.0542 (8) Åθ = 2.5–26.0°
b = 16.4104 (19) ŵ = 0.09 mm1
c = 21.635 (2) ÅT = 296 K
V = 2859.5 (5) Å3Block, colourless
Z = 80.41 × 0.32 × 0.21 mm
Data collection top
Bruker X8 APEXII area-detector
diffractometer
1919 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.033
Graphite monochromatorθmax = 26.0°, θmin = 2.5°
φ and ω scansh = 99
12894 measured reflectionsk = 2019
2783 independent reflectionsl = 2526
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)] = 0.052Hydrogen site location: difference Fourier map
wR(F2) = 0.170H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0849P)2 + 1.249P]
where P = (Fo2 + 2Fc2)/3
2783 reflections(Δ/σ)max < 0.001
190 parametersΔρmax = 0.35 e Å3
0 restraintsΔρmin = 0.36 e Å3
Crystal data top
C16H15N3O2V = 2859.5 (5) Å3
Mr = 281.31Z = 8
Orthorhombic, PbcaMo Kα radiation
a = 8.0542 (8) ŵ = 0.09 mm1
b = 16.4104 (19) ÅT = 296 K
c = 21.635 (2) Å0.41 × 0.32 × 0.21 mm
Data collection top
Bruker X8 APEXII area-detector
diffractometer
1919 reflections with I > 2σ(I)
12894 measured reflectionsRint = 0.033
2783 independent reflectionsθmax = 26.0°
Refinement top
R[F2 > 2σ(F2)] = 0.052H-atom parameters constrained
wR(F2) = 0.170Δρmax = 0.35 e Å3
S = 1.04Δρmin = 0.36 e Å3
2783 reflectionsAbsolute structure: ?
190 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
C10.7015 (3)0.59846 (13)0.00919 (11)0.0423 (5)
C20.4533 (2)0.62909 (13)0.03355 (10)0.0392 (5)
C30.2988 (3)0.66217 (13)0.04562 (11)0.0431 (5)
H30.24640.70410.02430.052*
C40.2383 (3)0.61938 (13)0.09644 (10)0.0404 (5)
C50.0780 (3)0.63145 (14)0.12822 (10)0.0426 (5)
C60.0290 (3)0.69261 (15)0.10875 (12)0.0531 (6)
H60.00020.72550.07550.064*
C70.1796 (3)0.70489 (17)0.13873 (14)0.0660 (8)
H70.25110.74560.12520.079*
C80.2234 (4)0.65694 (18)0.18851 (14)0.0689 (8)
H80.32430.66500.20850.083*
C90.1158 (3)0.5968 (2)0.20843 (13)0.0681 (8)
H90.14380.56490.24240.082*
C100.0323 (3)0.58363 (17)0.17833 (12)0.0557 (7)
H100.10250.54220.19170.067*
C110.6159 (3)0.52087 (13)0.07911 (10)0.0423 (5)
C120.7310 (3)0.53683 (14)0.03464 (11)0.0455 (6)
H120.82910.50700.03320.055*
C130.6281 (3)0.45638 (16)0.12736 (12)0.0584 (7)
H13A0.53080.45780.15300.088*
H13B0.72470.46580.15230.088*
H13C0.63650.40400.10790.088*
C140.8285 (3)0.61382 (15)0.05871 (12)0.0493 (6)
C150.8726 (4)0.6665 (2)0.15930 (14)0.0784 (9)
H15A0.96320.62760.16010.094*
H15B0.91910.72080.15580.094*
C160.7733 (6)0.6597 (3)0.21607 (16)0.1145 (15)
H16A0.84270.67000.25130.172*
H16B0.68480.69890.21500.172*
H16C0.72760.60580.21900.172*
N10.3450 (2)0.56159 (11)0.11673 (9)0.0435 (5)
N20.4760 (2)0.56790 (11)0.07779 (8)0.0395 (5)
N30.5670 (2)0.64421 (11)0.01033 (9)0.0424 (5)
O10.9709 (2)0.59496 (15)0.05385 (11)0.0868 (7)
O20.76394 (19)0.65002 (11)0.10746 (8)0.0575 (5)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0374 (11)0.0394 (12)0.0500 (14)0.0004 (9)0.0033 (9)0.0011 (11)
C20.0402 (11)0.0342 (11)0.0432 (13)0.0002 (9)0.0029 (9)0.0031 (10)
C30.0424 (11)0.0386 (12)0.0484 (14)0.0045 (9)0.0018 (10)0.0049 (10)
C40.0398 (11)0.0401 (11)0.0411 (13)0.0031 (9)0.0021 (9)0.0020 (10)
C50.0410 (11)0.0439 (12)0.0429 (13)0.0096 (9)0.0017 (9)0.0050 (11)
C60.0491 (13)0.0494 (14)0.0607 (16)0.0019 (11)0.0115 (11)0.0015 (12)
C70.0535 (14)0.0578 (16)0.087 (2)0.0039 (12)0.0200 (14)0.0032 (16)
C80.0566 (16)0.074 (2)0.076 (2)0.0108 (14)0.0254 (14)0.0131 (17)
C90.0625 (16)0.083 (2)0.0586 (18)0.0192 (15)0.0127 (13)0.0060 (15)
C100.0517 (13)0.0662 (16)0.0492 (15)0.0084 (12)0.0017 (11)0.0072 (13)
C110.0392 (11)0.0382 (12)0.0496 (14)0.0004 (9)0.0137 (9)0.0017 (11)
C120.0359 (10)0.0436 (13)0.0570 (15)0.0039 (9)0.0077 (10)0.0002 (12)
C130.0522 (14)0.0578 (15)0.0650 (17)0.0032 (12)0.0134 (12)0.0171 (13)
C140.0387 (12)0.0475 (13)0.0618 (16)0.0016 (10)0.0021 (10)0.0024 (12)
C150.0669 (17)0.101 (2)0.068 (2)0.0081 (17)0.0267 (15)0.0040 (18)
C160.124 (3)0.146 (4)0.073 (3)0.013 (3)0.020 (2)0.028 (3)
N10.0415 (9)0.0463 (11)0.0428 (11)0.0036 (8)0.0023 (8)0.0023 (9)
N20.0384 (9)0.0375 (10)0.0425 (11)0.0020 (7)0.0056 (8)0.0024 (8)
N30.0388 (9)0.0402 (10)0.0482 (11)0.0021 (8)0.0031 (8)0.0030 (9)
O10.0407 (10)0.1158 (18)0.1039 (17)0.0204 (10)0.0123 (10)0.0295 (14)
O20.0442 (9)0.0723 (12)0.0561 (11)0.0020 (8)0.0098 (8)0.0099 (10)
Geometric parameters (Å, º) top
C1—N31.318 (3)C9—H90.9300
C1—C121.407 (3)C10—H100.9300
C1—C141.503 (3)C11—C121.361 (3)
C2—N31.342 (3)C11—N21.366 (3)
C2—C31.383 (3)C11—C131.490 (3)
C2—N21.399 (3)C12—H120.9300
C3—C41.393 (3)C13—H13A0.9600
C3—H30.9300C13—H13B0.9600
C4—N11.353 (3)C13—H13C0.9600
C4—C51.476 (3)C14—O11.192 (3)
C5—C101.388 (3)C14—O21.318 (3)
C5—C61.389 (3)C15—O21.448 (3)
C6—C71.390 (3)C15—C161.470 (5)
C6—H60.9300C15—H15A0.9700
C7—C81.380 (4)C15—H15B0.9700
C7—H70.9300C16—H16A0.9600
C8—C91.382 (4)C16—H16B0.9600
C8—H80.9300C16—H16C0.9600
C9—C101.376 (4)N1—N21.354 (2)
N3—C1—C12124.1 (2)N2—C11—C13118.0 (2)
N3—C1—C14116.8 (2)C11—C12—C1120.0 (2)
C12—C1—C14119.09 (19)C11—C12—H12120.0
N3—C2—C3132.5 (2)C1—C12—H12120.0
N3—C2—N2121.83 (18)C11—C13—H13A109.5
C3—C2—N2105.69 (18)C11—C13—H13B109.5
C2—C3—C4105.43 (19)H13A—C13—H13B109.5
C2—C3—H3127.3C11—C13—H13C109.5
C4—C3—H3127.3H13A—C13—H13C109.5
N1—C4—C3112.77 (19)H13B—C13—H13C109.5
N1—C4—C5119.9 (2)O1—C14—O2124.6 (2)
C3—C4—C5127.3 (2)O1—C14—C1123.3 (2)
C10—C5—C6118.7 (2)O2—C14—C1112.16 (18)
C10—C5—C4121.3 (2)O2—C15—C16107.7 (3)
C6—C5—C4119.9 (2)O2—C15—H15A110.2
C5—C6—C7120.3 (2)C16—C15—H15A110.2
C5—C6—H6119.8O2—C15—H15B110.2
C7—C6—H6119.8C16—C15—H15B110.2
C8—C7—C6120.3 (3)H15A—C15—H15B108.5
C8—C7—H7119.8C15—C16—H16A109.5
C6—C7—H7119.8C15—C16—H16B109.5
C7—C8—C9119.4 (2)H16A—C16—H16B109.5
C7—C8—H8120.3C15—C16—H16C109.5
C9—C8—H8120.3H16A—C16—H16C109.5
C10—C9—C8120.5 (3)H16B—C16—H16C109.5
C10—C9—H9119.7C4—N1—N2103.87 (17)
C8—C9—H9119.7N1—N2—C11125.91 (18)
C9—C10—C5120.7 (3)N1—N2—C2112.24 (16)
C9—C10—H10119.6C11—N2—C2121.85 (18)
C5—C10—H10119.6C1—N3—C2116.24 (19)
C12—C11—N2115.98 (19)C14—O2—C15117.8 (2)
C12—C11—C13126.0 (2)
N3—C2—C3—C4178.2 (2)N3—C1—C14—O222.0 (3)
N2—C2—C3—C40.3 (2)C12—C1—C14—O2157.4 (2)
C2—C3—C4—N10.2 (3)C3—C4—N1—N20.1 (2)
C2—C3—C4—C5179.4 (2)C5—C4—N1—N2179.70 (18)
N1—C4—C5—C101.1 (3)C4—N1—N2—C11178.94 (19)
C3—C4—C5—C10179.3 (2)C4—N1—N2—C20.3 (2)
N1—C4—C5—C6177.8 (2)C12—C11—N2—N1178.77 (19)
C3—C4—C5—C61.8 (3)C13—C11—N2—N10.0 (3)
C10—C5—C6—C70.6 (4)C12—C11—N2—C20.4 (3)
C4—C5—C6—C7179.4 (2)C13—C11—N2—C2179.1 (2)
C5—C6—C7—C80.6 (4)N3—C2—N2—N1178.54 (18)
C6—C7—C8—C90.3 (4)C3—C2—N2—N10.4 (2)
C7—C8—C9—C101.2 (4)N3—C2—N2—C110.7 (3)
C8—C9—C10—C51.3 (4)C3—C2—N2—C11178.88 (19)
C6—C5—C10—C90.4 (4)C12—C1—N3—C20.4 (3)
C4—C5—C10—C9178.5 (2)C14—C1—N3—C2179.02 (19)
N2—C11—C12—C10.3 (3)C3—C2—N3—C1177.9 (2)
C13—C11—C12—C1178.3 (2)N2—C2—N3—C10.3 (3)
N3—C1—C12—C110.7 (3)O1—C14—O2—C151.4 (4)
C14—C1—C12—C11178.7 (2)C1—C14—O2—C15178.5 (2)
N3—C1—C14—O1158.1 (3)C16—C15—O2—C14147.1 (3)
C12—C1—C14—O122.5 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C12—H12···O1i0.932.363.258 (3)161
C6—H6···N3ii0.932.623.507 (3)161
Symmetry codes: (i) x+2, y+1, z; (ii) x1/2, y+3/2, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C12—H12···O1i0.932.363.258 (3)160.9
C6—H6···N3ii0.932.623.507 (3)160.6
Symmetry codes: (i) x+2, y+1, z; (ii) x1/2, y+3/2, z.
Acknowledgements top

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

references
References top

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