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

Journal logoIUCrDATA
ISSN: 2414-3146

1-Methyl-4-phenyl-1H-pyrazolo­[3,4-d]pyrimidine

aLaboratoire de Chimie Organique Hétérocyclique, Centre de Recherche Des Sciences des Médicaments, Pôle de Compétence Pharmacochimie, Av Ibn Battouta, BP 1014, Faculté des Sciences, Université Mohammed V, Rabat, Morocco, bLaboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco, and cDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
*Correspondence e-mail: elhafi.mohamed1@gmail.com

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 25 August 2017; accepted 26 August 2017; online 5 September 2017)

In the crystal, mol­ecules of the title compound, C12H10N4, stack in a head-to-tail manner along the b direction through ππ stacking inter­actions between both portions of the pyrazolo­pyrimidine ring system.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

During the last decade, considerable inter­est has been paid to the chemistry of pyrazolo­[3,4-d]pyrimidines. This is undoubtedly due to a broad variety of biological activities of pyrazolo­[3,4-d]pyrimidine derivatives, such as their action as anti­tubercular (Trivedi et al., 2012[Trivedi, A. R., Dholariya, B. H., Vakhariya, C. P., Dodiya, D. K., Ram, H. K., Kataria, V. B., Siddiqui, A. B. & Shah, V. H. (2012). Med. Chem. Res. 21, 1887-1891.]), anti­bacterial (Rostamizadeh et al., 2013[Rostamizadeh, S., Nojavan, M., Aryan, R., Sadeghian, H. & Davoodnejad, M. (2013). Chin. Chem. Lett. 24, 629-632.]) and anti­tumor agents (Intori et al., 2015[Intori, C., Fallacara, A. L., Radi, M., Zamperini, C., Dreassi, E., Crespan, E., Maga, G., Schenone, S., Musumeci, F. & Brullo, C. (2015). J. Med. Chem. 58, 347-361.]). The present work is a continuation of the investigation of pyrazolo­[3,4-d]pyrimidine derivatives reported by our team (Alsubari et al., 2011[Alsubari, A., Ramli, Y., Essassi, E. M. & Zouihri, H. (2011). Acta Cryst. E67, o1926.]).

The fused heterobicyclic ring system (Fig. 1[link]) shows maximum deviations of 0.0257 (1) and −0.0270 (1) Å from the least-squares plane through the nine atoms (r.m.s. deviation = 0.0209 Å). The dihedral angle between this plane and that of the phenyl ring is 33.43 (4)°. In the crystal, mol­ecules stack along the b-axis direction in a head-to-tail fashion through ππ stacking inter­actions of the bicyclic core (Fig. 2[link]). The dihedral angle between the five- and six-membered rings in each inter­action is 2.30 (7)°, while the centroid–centroid distances alternate between 3.509 (1) and 3.645 (1) Å along the stack. In addition, there are C8—H8⋯π(ring) (ring = C7–C12, H⋯centroid = 2.93 Å and C—H⋯centroid = 148°) inter­actions on the outside of the stacks which are responsible in part for the orientation of the phenyl ring relative to the bicyclic core (Fig. 3[link]).

[Figure 1]
Figure 1
The title mol­ecule, with the atom-labelling scheme and 25% probability ellipsoids.
[Figure 2]
Figure 2
Detail of the ππ stacking (orange dotted lines) and the C—H⋯π(ring) (purple dotted lines) inter­actions forming stacks along the b direction. H atoms not involved in the inter­actions have been omitted for clarity.
[Figure 3]
Figure 3
Packing viewed along the b direction. H atoms have been omitted for clarity.

Synthesis and crystallization

To a microwave vial was added 1-methyl-4-chloro-1H-pyra­zolo­[3,4-d]pyrimidine (50 mg, 0.3 mmol), phenyl­boronic acid (40.23 mg, 0.33 mmol), K2CO3 (124.38 mg, 0.9 mmol), [1,1′-bis­(di­phenyl­phosphino)ferrocene]di­chloro­palladium(II) or PdCl2(dppf) (22 mg, 0.03 mmol), THF (3 ml) and H2O (10 µl). The reaction mixture was heated with stirring in a microwave reactor at 443 K for 10 min. The crude reaction mixture was passed through a small silica-gel plug, eluting with EtOAc, and the crude material was purified by silica-gel chromatography (0 to 10% EtOAc gradient in hexa­nes). The title compound was recrystallized from ethanol, at room temperature, giving colourless crystals (yield 80%; m.p. 388–390 K).

Refinement

Crystal and refinement data are presented in Table 1[link].

Table 1
Experimental details

Crystal data
Chemical formula C12H10N4
Mr 210.24
Crystal system, space group Orthorhombic, Pbca
Temperature (K) 296
a, b, c (Å) 14.6205 (10), 7.1497 (5), 20.3532 (15)
V3) 2127.6 (3)
Z 8
Radiation type Mo Kα
μ (mm−1) 0.08
Crystal size (mm) 0.29 × 0.20 × 0.16
 
Data collection
Diffractometer Bruker SMART APEX CCD
Absorption correction Multi-scan (SADABS; Bruker, 2016[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.86, 0.99
No. of measured, independent and observed [I > 2σ(I)] reflections 18616, 2639, 1725
Rint 0.043
(sin θ/λ)max−1) 0.667
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.139, 1.06
No. of reflections 2639
No. of parameters 147
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.20, −0.14
Computer programs: APEX3 (Bruker, 2016[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SAINT (Bruker, 2016[Bruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), DIAMOND (Brandenburg & Putz, 2012[Brandenburg, K. & Putz, H. (2012). DIAMOND. Crystal Impact GbR, Bonn, Germany.]) and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]).

Structural data


Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Bruker, 2016).

1-Methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine top
Crystal data top
C12H10N4Dx = 1.313 Mg m3
Mr = 210.24Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PbcaCell parameters from 4337 reflections
a = 14.6205 (10) Åθ = 2.4–24.3°
b = 7.1497 (5) ŵ = 0.08 mm1
c = 20.3532 (15) ÅT = 296 K
V = 2127.6 (3) Å3Column, colourless
Z = 80.29 × 0.20 × 0.16 mm
F(000) = 880
Data collection top
Bruker SMART APEX CCD
diffractometer
2639 independent reflections
Radiation source: fine-focus sealed tube1725 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.043
Detector resolution: 8.3333 pixels mm-1θmax = 28.3°, θmin = 2.0°
φ and ω scansh = 1919
Absorption correction: multi-scan
(SADABS; Bruker, 2016)
k = 99
Tmin = 0.86, Tmax = 0.99l = 2726
18616 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.044H-atom parameters constrained
wR(F2) = 0.139 w = 1/[σ2(Fo2) + (0.0655P)2 + 0.1279P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
2639 reflectionsΔρmax = 0.20 e Å3
147 parametersΔρmin = 0.14 e Å3
0 restraintsExtinction correction: SHELXL2014 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0053 (13)
Special details top

Experimental. The diffraction data were collected in three sets of 363 frames (0.5° width in ω) at φ = 0, 120 and 240°. A scan time of 40 sec/frame was used.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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. H-atoms attached to carbon were placed in calculated positions (C—H = 0.93 - 0.97 Å). All were included as riding contributions with isotropic displacement parameters 1.2 times those of the attached atoms.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.40768 (7)0.80901 (19)0.41811 (6)0.0650 (4)
N20.31476 (8)0.87710 (17)0.51276 (6)0.0621 (3)
N30.15455 (7)0.85635 (16)0.49050 (6)0.0582 (3)
N40.09970 (8)0.8116 (2)0.43846 (6)0.0670 (4)
C10.24717 (8)0.80131 (17)0.40626 (6)0.0475 (3)
C20.33514 (9)0.78419 (17)0.37892 (7)0.0505 (3)
C30.39276 (10)0.8529 (2)0.48141 (8)0.0704 (4)
H30.44510.86850.50680.084*
C40.24321 (8)0.84873 (17)0.47294 (7)0.0493 (3)
C50.15443 (9)0.77896 (19)0.38832 (7)0.0574 (4)
H50.13460.74550.34650.069*
C60.11689 (12)0.8901 (3)0.55525 (7)0.0776 (5)
H6A0.06360.96780.55150.116*
H6B0.16170.95190.58200.116*
H6C0.10040.77310.57510.116*
C70.35299 (10)0.73913 (17)0.30951 (6)0.0546 (4)
C80.29471 (11)0.7977 (2)0.26000 (7)0.0671 (4)
H80.24270.86640.27050.081*
C90.31320 (15)0.7549 (3)0.19521 (8)0.0852 (6)
H90.27410.79610.16220.102*
C100.38869 (16)0.6522 (3)0.17949 (9)0.0936 (6)
H100.40030.62190.13580.112*
C110.44746 (14)0.5936 (2)0.22764 (9)0.0861 (5)
H110.49900.52420.21660.103*
C120.43046 (10)0.6371 (2)0.29249 (7)0.0665 (4)
H120.47090.59810.32500.080*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0461 (7)0.0821 (9)0.0667 (7)0.0000 (5)0.0014 (5)0.0019 (6)
N20.0523 (7)0.0758 (8)0.0583 (7)0.0049 (5)0.0055 (5)0.0033 (6)
N30.0458 (6)0.0708 (7)0.0580 (7)0.0006 (5)0.0031 (5)0.0006 (5)
N40.0459 (7)0.0877 (9)0.0675 (8)0.0034 (6)0.0042 (5)0.0008 (6)
C10.0454 (7)0.0433 (6)0.0538 (7)0.0003 (5)0.0030 (5)0.0033 (5)
C20.0474 (7)0.0452 (7)0.0588 (7)0.0016 (5)0.0006 (6)0.0041 (5)
C30.0483 (8)0.0932 (11)0.0697 (9)0.0054 (7)0.0108 (7)0.0041 (8)
C40.0459 (7)0.0468 (7)0.0553 (7)0.0011 (5)0.0017 (6)0.0032 (5)
C50.0494 (7)0.0650 (9)0.0578 (8)0.0032 (6)0.0061 (6)0.0011 (6)
C60.0628 (9)0.1040 (13)0.0661 (10)0.0007 (9)0.0138 (7)0.0065 (8)
C70.0588 (8)0.0477 (7)0.0573 (8)0.0024 (5)0.0073 (6)0.0046 (6)
C80.0747 (10)0.0648 (9)0.0619 (9)0.0045 (7)0.0022 (7)0.0096 (7)
C90.1075 (15)0.0887 (13)0.0592 (10)0.0010 (10)0.0010 (9)0.0129 (9)
C100.1308 (17)0.0880 (12)0.0620 (10)0.0013 (12)0.0268 (11)0.0010 (9)
C110.1003 (13)0.0744 (11)0.0835 (11)0.0083 (9)0.0372 (10)0.0005 (9)
C120.0638 (9)0.0646 (9)0.0712 (10)0.0051 (7)0.0152 (7)0.0054 (7)
Geometric parameters (Å, º) top
N1—C21.3388 (17)C6—H6A0.9600
N1—C31.344 (2)C6—H6B0.9600
N2—C31.3181 (18)C6—H6C0.9600
N2—C41.3387 (17)C7—C81.385 (2)
N3—C41.3458 (16)C7—C121.391 (2)
N3—N41.3665 (16)C8—C91.380 (2)
N3—C61.4486 (18)C8—H80.9300
N4—C51.3176 (18)C9—C101.363 (3)
C1—C41.4001 (19)C9—H90.9300
C1—C21.4068 (18)C10—C111.369 (3)
C1—C51.4132 (18)C10—H100.9300
C2—C71.4722 (19)C11—C121.379 (2)
C3—H30.9300C11—H110.9300
C5—H50.9300C12—H120.9300
C2—N1—C3118.27 (11)H6A—C6—H6B109.5
C3—N2—C4111.29 (12)N3—C6—H6C109.5
C4—N3—N4110.49 (11)H6A—C6—H6C109.5
C4—N3—C6127.91 (12)H6B—C6—H6C109.5
N4—N3—C6121.42 (12)C8—C7—C12118.58 (13)
C5—N4—N3106.58 (11)C8—C7—C2121.55 (13)
C4—C1—C2116.25 (11)C12—C7—C2119.87 (13)
C4—C1—C5103.78 (11)C9—C8—C7120.51 (16)
C2—C1—C5139.92 (13)C9—C8—H8119.7
N1—C2—C1118.49 (12)C7—C8—H8119.7
N1—C2—C7117.41 (12)C10—C9—C8120.14 (18)
C1—C2—C7124.10 (12)C10—C9—H9119.9
N2—C3—N1129.43 (13)C8—C9—H9119.9
N2—C3—H3115.3C9—C10—C11120.32 (17)
N1—C3—H3115.3C9—C10—H10119.8
N2—C4—N3125.86 (12)C11—C10—H10119.8
N2—C4—C1126.24 (12)C10—C11—C12120.20 (17)
N3—C4—C1107.88 (11)C10—C11—H11119.9
N4—C5—C1111.26 (12)C12—C11—H11119.9
N4—C5—H5124.4C11—C12—C7120.24 (16)
C1—C5—H5124.4C11—C12—H12119.9
N3—C6—H6A109.5C7—C12—H12119.9
N3—C6—H6B109.5
C4—N3—N4—C50.93 (16)C2—C1—C4—N3179.22 (11)
C6—N3—N4—C5176.30 (14)C5—C1—C4—N31.27 (13)
C3—N1—C2—C11.3 (2)N3—N4—C5—C10.09 (16)
C3—N1—C2—C7179.06 (13)C4—C1—C5—N40.73 (15)
C4—C1—C2—N11.71 (18)C2—C1—C5—N4177.88 (15)
C5—C1—C2—N1175.20 (15)N1—C2—C7—C8147.81 (14)
C4—C1—C2—C7178.72 (11)C1—C2—C7—C832.62 (19)
C5—C1—C2—C74.4 (2)N1—C2—C7—C1231.51 (18)
C4—N2—C3—N11.1 (2)C1—C2—C7—C12148.06 (13)
C2—N1—C3—N20.2 (3)C12—C7—C8—C90.2 (2)
C3—N2—C4—N3177.61 (13)C2—C7—C8—C9179.54 (14)
C3—N2—C4—C10.6 (2)C7—C8—C9—C100.8 (3)
N4—N3—C4—N2177.11 (13)C8—C9—C10—C111.1 (3)
C6—N3—C4—N22.1 (2)C9—C10—C11—C120.4 (3)
N4—N3—C4—C11.41 (14)C10—C11—C12—C70.7 (3)
C6—N3—C4—C1176.39 (14)C8—C7—C12—C111.0 (2)
C2—C1—C4—N20.72 (19)C2—C7—C12—C11179.70 (14)
C5—C1—C4—N2177.24 (13)
 

Acknowledgements

JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.

References

First citationAlsubari, A., Ramli, Y., Essassi, E. M. & Zouihri, H. (2011). Acta Cryst. E67, o1926.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationBrandenburg, K. & Putz, H. (2012). DIAMOND. Crystal Impact GbR, Bonn, Germany.  Google Scholar
First citationBruker (2016). APEX3, SADABS and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationIntori, C., Fallacara, A. L., Radi, M., Zamperini, C., Dreassi, E., Crespan, E., Maga, G., Schenone, S., Musumeci, F. & Brullo, C. (2015). J. Med. Chem. 58, 347–361.  Web of Science PubMed Google Scholar
First citationRostamizadeh, S., Nojavan, M., Aryan, R., Sadeghian, H. & Davoodnejad, M. (2013). Chin. Chem. Lett. 24, 629–632.  Web of Science CrossRef CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationTrivedi, A. R., Dholariya, B. H., Vakhariya, C. P., Dodiya, D. K., Ram, H. K., Kataria, V. B., Siddiqui, A. B. & Shah, V. H. (2012). Med. Chem. Res. 21, 1887–1891.  Web of Science CrossRef CAS Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoIUCrDATA
ISSN: 2414-3146
Follow IUCr Journals
Sign up for e-alerts
Follow IUCr on Twitter
Follow us on facebook
Sign up for RSS feeds

[# https x2 cm 20170801 %]