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

El Hafi, M.; Boulhaoua, M.; Essaghouani, A.; Ramli, Y.; Essassi, E.M.; Mague, J.T.

doi:10.1107/S241431461701238X

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 9| September 2017| x171238

https://doi.org/10.1107/S241431461701238X

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

Mohamed El Hafi,^a ^* Mohammed Boulhaoua,^a Abdelhanine Essaghouani,^a Youssef Ramli,^b El Mokhtar Essassi ^a and Joel T. Mague ^c

^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 π–π stacking interactions between both portions of the pyrazolopyrimidine ring system.

Keywords: crystal structure; π–π stacking; pyrimidine.

CCDC reference: 1570983

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 ), antibacterial (Rostamizadeh et al., 2013 ) and antitumor agents (Intori et al., 2015 ). The present work is a continuation of the investigation of pyrazolo[3,4-d]pyrimidine derivatives reported by our team (Alsubari et al., 2011 ).

The fused heterobicyclic ring system (Fig. 1) 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 π–π stacking interactions of the bicyclic core (Fig. 2). 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).

Figure 1
The title molecule, with the atom-labelling scheme and 25% probability ellipsoids.

Figure 2
Detail of the π–π 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
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.

Table 1
Experimental details

Crystal data
Chemical formula	C₁₂H₁₀N₄
M_r	210.24
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	296
a, b, c (Å)	14.6205 (10), 7.1497 (5), 20.3532 (15)
V (Å³)	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 )
T_min, T_max	0.86, 0.99
No. of measured, independent and observed [I > 2σ(I)] reflections	18616, 2639, 1725
R_int	0.043
(sin θ/λ)_max (Å⁻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
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.14
Computer programs: APEX3 (Bruker, 2016), SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), DIAMOND (Brandenburg & Putz, 2012 ) and SHELXTL (Sheldrick, 2008 ).

Structural data

CCDC reference: 1570983

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S241431461701238X/vm4027sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S241431461701238X/vm4027Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S241431461701238X/vm4027Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S241431461701238X/vm4027Isup4.cml

checkCIF report

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

C₁₂H₁₀N₄	D_x = 1.313 Mg m⁻³
M_r = 210.24	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 4337 reflections
a = 14.6205 (10) Å	θ = 2.4–24.3°
b = 7.1497 (5) Å	µ = 0.08 mm⁻¹
c = 20.3532 (15) Å	T = 296 K
V = 2127.6 (3) Å³	Column, colourless
Z = 8	0.29 × 0.20 × 0.16 mm
F(000) = 880

Data collection top

Bruker SMART APEX CCD diffractometer	2639 independent reflections
Radiation source: fine-focus sealed tube	1725 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.043
Detector resolution: 8.3333 pixels mm^-1	θ_max = 28.3°, θ_min = 2.0°
φ and ω scans	h = −19→19
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −9→9
T_min = 0.86, T_max = 0.99	l = −27→26
18616 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.044	H-atom parameters constrained
wR(F²) = 0.139	w = 1/[σ²(F_o²) + (0.0655P)² + 0.1279P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
2639 reflections	Δρ_max = 0.20 e Å⁻³
147 parameters	Δρ_min = −0.14 e Å⁻³
0 restraints	Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction 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

	x	y	z	U_iso*/U_eq
N1	0.40768 (7)	0.80901 (19)	0.41811 (6)	0.0650 (4)
N2	0.31476 (8)	0.87710 (17)	0.51276 (6)	0.0621 (3)
N3	0.15455 (7)	0.85635 (16)	0.49050 (6)	0.0582 (3)
N4	0.09970 (8)	0.8116 (2)	0.43846 (6)	0.0670 (4)
C1	0.24717 (8)	0.80131 (17)	0.40626 (6)	0.0475 (3)
C2	0.33514 (9)	0.78419 (17)	0.37892 (7)	0.0505 (3)
C3	0.39276 (10)	0.8529 (2)	0.48141 (8)	0.0704 (4)
H3	0.4451	0.8685	0.5068	0.084*
C4	0.24321 (8)	0.84873 (17)	0.47294 (7)	0.0493 (3)
C5	0.15443 (9)	0.77896 (19)	0.38832 (7)	0.0574 (4)
H5	0.1346	0.7455	0.3465	0.069*
C6	0.11689 (12)	0.8901 (3)	0.55525 (7)	0.0776 (5)
H6A	0.0636	0.9678	0.5515	0.116*
H6B	0.1617	0.9519	0.5820	0.116*
H6C	0.1004	0.7731	0.5751	0.116*
C7	0.35299 (10)	0.73913 (17)	0.30951 (6)	0.0546 (4)
C8	0.29471 (11)	0.7977 (2)	0.26000 (7)	0.0671 (4)
H8	0.2427	0.8664	0.2705	0.081*
C9	0.31320 (15)	0.7549 (3)	0.19521 (8)	0.0852 (6)
H9	0.2741	0.7961	0.1622	0.102*
C10	0.38869 (16)	0.6522 (3)	0.17949 (9)	0.0936 (6)
H10	0.4003	0.6219	0.1358	0.112*
C11	0.44746 (14)	0.5936 (2)	0.22764 (9)	0.0861 (5)
H11	0.4990	0.5242	0.2166	0.103*
C12	0.43046 (10)	0.6371 (2)	0.29249 (7)	0.0665 (4)
H12	0.4709	0.5981	0.3250	0.080*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0461 (7)	0.0821 (9)	0.0667 (7)	0.0000 (5)	−0.0014 (5)	−0.0019 (6)
N2	0.0523 (7)	0.0758 (8)	0.0583 (7)	−0.0049 (5)	−0.0055 (5)	−0.0033 (6)
N3	0.0458 (6)	0.0708 (7)	0.0580 (7)	−0.0006 (5)	0.0031 (5)	−0.0006 (5)
N4	0.0459 (7)	0.0877 (9)	0.0675 (8)	−0.0034 (6)	−0.0042 (5)	0.0008 (6)
C1	0.0454 (7)	0.0433 (6)	0.0538 (7)	−0.0003 (5)	−0.0030 (5)	0.0033 (5)
C2	0.0474 (7)	0.0452 (7)	0.0588 (7)	0.0016 (5)	−0.0006 (6)	0.0041 (5)
C3	0.0483 (8)	0.0932 (11)	0.0697 (9)	−0.0054 (7)	−0.0108 (7)	−0.0041 (8)
C4	0.0459 (7)	0.0468 (7)	0.0553 (7)	−0.0011 (5)	−0.0017 (6)	0.0032 (5)
C5	0.0494 (7)	0.0650 (9)	0.0578 (8)	−0.0032 (6)	−0.0061 (6)	0.0011 (6)
C6	0.0628 (9)	0.1040 (13)	0.0661 (10)	0.0007 (9)	0.0138 (7)	−0.0065 (8)
C7	0.0588 (8)	0.0477 (7)	0.0573 (8)	−0.0024 (5)	0.0073 (6)	0.0046 (6)
C8	0.0747 (10)	0.0648 (9)	0.0619 (9)	0.0045 (7)	0.0022 (7)	0.0096 (7)
C9	0.1075 (15)	0.0887 (13)	0.0592 (10)	−0.0010 (10)	0.0010 (9)	0.0129 (9)
C10	0.1308 (17)	0.0880 (12)	0.0620 (10)	−0.0013 (12)	0.0268 (11)	0.0010 (9)
C11	0.1003 (13)	0.0744 (11)	0.0835 (11)	0.0083 (9)	0.0372 (10)	0.0005 (9)
C12	0.0638 (9)	0.0646 (9)	0.0712 (10)	0.0051 (7)	0.0152 (7)	0.0054 (7)

Geometric parameters (Å, º) top

N1—C2	1.3388 (17)	C6—H6A	0.9600
N1—C3	1.344 (2)	C6—H6B	0.9600
N2—C3	1.3181 (18)	C6—H6C	0.9600
N2—C4	1.3387 (17)	C7—C8	1.385 (2)
N3—C4	1.3458 (16)	C7—C12	1.391 (2)
N3—N4	1.3665 (16)	C8—C9	1.380 (2)
N3—C6	1.4486 (18)	C8—H8	0.9300
N4—C5	1.3176 (18)	C9—C10	1.363 (3)
C1—C4	1.4001 (19)	C9—H9	0.9300
C1—C2	1.4068 (18)	C10—C11	1.369 (3)
C1—C5	1.4132 (18)	C10—H10	0.9300
C2—C7	1.4722 (19)	C11—C12	1.379 (2)
C3—H3	0.9300	C11—H11	0.9300
C5—H5	0.9300	C12—H12	0.9300

C2—N1—C3	118.27 (11)	H6A—C6—H6B	109.5
C3—N2—C4	111.29 (12)	N3—C6—H6C	109.5
C4—N3—N4	110.49 (11)	H6A—C6—H6C	109.5
C4—N3—C6	127.91 (12)	H6B—C6—H6C	109.5
N4—N3—C6	121.42 (12)	C8—C7—C12	118.58 (13)
C5—N4—N3	106.58 (11)	C8—C7—C2	121.55 (13)
C4—C1—C2	116.25 (11)	C12—C7—C2	119.87 (13)
C4—C1—C5	103.78 (11)	C9—C8—C7	120.51 (16)
C2—C1—C5	139.92 (13)	C9—C8—H8	119.7
N1—C2—C1	118.49 (12)	C7—C8—H8	119.7
N1—C2—C7	117.41 (12)	C10—C9—C8	120.14 (18)
C1—C2—C7	124.10 (12)	C10—C9—H9	119.9
N2—C3—N1	129.43 (13)	C8—C9—H9	119.9
N2—C3—H3	115.3	C9—C10—C11	120.32 (17)
N1—C3—H3	115.3	C9—C10—H10	119.8
N2—C4—N3	125.86 (12)	C11—C10—H10	119.8
N2—C4—C1	126.24 (12)	C10—C11—C12	120.20 (17)
N3—C4—C1	107.88 (11)	C10—C11—H11	119.9
N4—C5—C1	111.26 (12)	C12—C11—H11	119.9
N4—C5—H5	124.4	C11—C12—C7	120.24 (16)
C1—C5—H5	124.4	C11—C12—H12	119.9
N3—C6—H6A	109.5	C7—C12—H12	119.9
N3—C6—H6B	109.5

C4—N3—N4—C5	−0.93 (16)	C2—C1—C4—N3	−179.22 (11)
C6—N3—N4—C5	−176.30 (14)	C5—C1—C4—N3	−1.27 (13)
C3—N1—C2—C1	−1.3 (2)	N3—N4—C5—C1	0.09 (16)
C3—N1—C2—C7	179.06 (13)	C4—C1—C5—N4	0.73 (15)
C4—C1—C2—N1	1.71 (18)	C2—C1—C5—N4	177.88 (15)
C5—C1—C2—N1	−175.20 (15)	N1—C2—C7—C8	−147.81 (14)
C4—C1—C2—C7	−178.72 (11)	C1—C2—C7—C8	32.62 (19)
C5—C1—C2—C7	4.4 (2)	N1—C2—C7—C12	31.51 (18)
C4—N2—C3—N1	1.1 (2)	C1—C2—C7—C12	−148.06 (13)
C2—N1—C3—N2	−0.2 (3)	C12—C7—C8—C9	0.2 (2)
C3—N2—C4—N3	177.61 (13)	C2—C7—C8—C9	179.54 (14)
C3—N2—C4—C1	−0.6 (2)	C7—C8—C9—C10	0.8 (3)
N4—N3—C4—N2	−177.11 (13)	C8—C9—C10—C11	−1.1 (3)
C6—N3—C4—N2	−2.1 (2)	C9—C10—C11—C12	0.4 (3)
N4—N3—C4—C1	1.41 (14)	C10—C11—C12—C7	0.7 (3)
C6—N3—C4—C1	176.39 (14)	C8—C7—C12—C11	−1.0 (2)
C2—C1—C4—N2	−0.72 (19)	C2—C7—C12—C11	179.70 (14)
C5—C1—C4—N2	177.24 (13)

Acknowledgements

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

References

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