6-Amino-3-methyl-1-phenyl-1H-pyrazolo­[3,4-b]pyrazine-5-carboxamide

Kaur, M.; Mohamed, S.K.; Akkurt, M.; Jasinski, J.P.; El-Emary, T.I.; Albayati, M.R.

doi:10.1107/S2414314616017429

organic compounds

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ISSN: 2414-3146

Volume 1| Part 11| November 2016| x161742

https://doi.org/10.1107/S2414314616017429

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6-Amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyrazine-5-carboxamide

Manpreet Kaur,^a Shaaban K. Mohamed,^b,^c Mehmet Akkurt,^d Jerry P. Jasinski,^a Talaat I. El-Emary ^e and Mustafa R. Albayati ^f ^*

^aDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA, ^bChemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, ^cChemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt, ^dDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, ^eDepartment of Chemistry, Faculty of Science, Assiut University, 71515 Assiut, Egypt, and ^fKirkuk University, College of Science, Department of Chemistry, Kirkuk, Iraq
^*Correspondence e-mail: shaabankamel@yahoo.com

Edited by E. R. T. Tiekink, Sunway University, Malaysia (Received 30 October 2016; accepted 31 October 2016; online 4 November 2016)

In the title compound, C₁₃H₁₂N₆O, the pyrazolo[3,4-b]pyrazine ring system is planar (r.m.s. deviation for the nine fitted atoms = 0.024 Å) and makes a dihedral angle of 5.72 (6)° with the pendent phenyl ring. The molecular conformation is stabilized by intramolecular N—H⋯O and C—H⋯N hydrogen bonds, each generating an S(6) loop. In the crystal, pairs of molecules are connected into inversion dimers by strong N—H⋯O hydrogen bonds, forming R₂²(8) ring motifs. These are linked into sheets parallel to (100) via N—H⋯N hydrogen bonds; π–π interactions between symmetry-related pyrazole and phenyl rings [centroid–centroid distances = 3.4453 (9) Å] within the sheets are also noted.

Keywords: crystal structure; 1H-pyrazole; pyrazine; 1H-pyrazolo[3,4-b]pyrazine.

CCDC reference: 1513135

Structure description

Pyrazole-containing compounds have been shown to exhibit numerous biological activities such as anti-inflammatory (Süküroğlu et al., 2005 ), antimalarial (Cunico et al., 2006 ), antitumor (Naito, et al., 2002 ), antibacterial, antifungal (Akbas et al., 2005 ; El-Emary, 2006 ), antiparasitic (El-Kashef et al., 2000 ; Rathelot et al., 2002 ) and antiviral (Ding et al., 1994 ). This led to the structure determination of the title compound (Fig. 1).

Figure 1
The title compound, with 50% probability displacement ellipsoids.

The pyrazolo[3,4-b]pyrazine ring system of the title compound is essentially planar with puckering parameters Q(2) = 0.0552 (15) Å and φ(2) = 251.1 (15)°. It is inclined to the phenyl ring with a dihedral angle of 5.72 (6)°. The bond lengths and bond angles of the title compound are normal and are in agreement with those reported for a similar compound (Mague et al., 2014 ). Intramolecular C—H⋯N and N—H⋯O hydrogen bonds form S(6) loop systems (Table 1, Fig. 2), stabilizing the molecular conformation.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2B⋯O1	0.93 (2)	1.97 (2)	2.6878 (18)	132.1 (17)
C13—H13⋯N3	0.95	2.31	2.985 (2)	127
N1—H1A⋯O1ⁱ	0.88	2.07	2.9488 (18)	175
N2—H2A⋯N2ⁱⁱ	0.86	2.50	3.345 (2)	167
Symmetry codes: (i) -x+1, -y+3, -z+1; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Figure 2
A view down the b axis of the unit-cell contents of the title compound. Dashed lines indicate hydrogen bonds.

In the crystal, pairs of molecules are connected into inversion dimers by N—H⋯O hydrogen bonds, leading to $[R_{2}^{2}]$ (8) ring motifs. These dimers are linked by N—H⋯N hydrogen bonds, leading to the formation of sheets parallel to the bc plane. Further connections within sheets are via π–π interactions between symmetry-related pyrazole and phenyl rings [centroid–centroid distances = 3.4453 (9) Å; symmetry operation: x, 1 + y, z].

Synthesis and crystallization

The title compound was prepared according to our reported method (El-Emary, 2007 ). Crystals for X-ray diffraction analysis were obtained by slow evaporation of a dimethyl sulfoxide solution of the compound.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₃H₁₂N₆O
M_r	268.29
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	173
a, b, c (Å)	14.7907 (5), 4.80351 (15), 17.1203 (8)
β (°)	92.067 (4)
V (Å³)	1215.57 (8)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.83
Crystal size (mm)	0.38 × 0.08 × 0.08

Data collection
Diffractometer	Rigaku Oxford Diffraction
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2014 )
T_min, T_max	0.909, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4156, 2307, 2011
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.615

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.112, 1.06
No. of reflections	2307
No. of parameters	187
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.27
Computer programs: CrysAlis PRO (Agilent, 2014), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1513135

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314616017429/tk4024sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314616017429/tk4024Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314616017429/tk4024Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

6-Amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyrazine-5-carboxamide top

Crystal data top

C₁₃H₁₂N₆O	F(000) = 560
M_r = 268.29	D_x = 1.466 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 14.7907 (5) Å	Cell parameters from 1708 reflections
b = 4.80351 (15) Å	θ = 3.9–71.0°
c = 17.1203 (8) Å	µ = 0.83 mm⁻¹
β = 92.067 (4)°	T = 173 K
V = 1215.57 (8) Å³	Needle, yellow
Z = 4	0.38 × 0.08 × 0.08 mm

Data collection top

Rigaku Oxford Diffraction diffractometer	2307 independent reflections
Radiation source: Enhance (Cu) X-ray Source	2011 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.030
Detector resolution: 16.0416 pixels mm^-1	θ_max = 71.4°, θ_min = 5.2°
ω scans	h = −13→18
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −5→3
T_min = 0.909, T_max = 1.000	l = −18→20
4156 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.112	w = 1/[σ²(F_o²) + (0.0562P)² + 0.3905P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max = 0.001
2307 reflections	Δρ_max = 0.22 e Å⁻³
187 parameters	Δρ_min = −0.27 e Å⁻³
0 restraints

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.49400 (7)	1.2243 (2)	0.57401 (7)	0.0261 (3)
N1	0.61528 (9)	1.3370 (3)	0.50430 (8)	0.0259 (3)
H1A	0.5852	1.4680	0.4785	0.031*
H1B	0.6724	1.3050	0.4945	0.031*
N2	0.51127 (9)	0.8234 (3)	0.68305 (9)	0.0264 (3)
H2A	0.4974	0.6859	0.7128	0.032*
N3	0.64619 (8)	0.5919 (3)	0.69322 (7)	0.0188 (3)
N4	0.71717 (8)	0.9523 (3)	0.57703 (7)	0.0186 (3)
N5	0.88003 (8)	0.4818 (3)	0.66020 (7)	0.0203 (3)
N6	0.80080 (8)	0.4173 (3)	0.69785 (7)	0.0185 (3)
C1	0.57451 (10)	1.1873 (3)	0.55802 (9)	0.0201 (3)
C2	0.63173 (10)	0.9704 (3)	0.59852 (8)	0.0187 (3)
C3	0.59627 (10)	0.7917 (3)	0.65810 (9)	0.0189 (3)
C4	0.73170 (10)	0.5843 (3)	0.67103 (8)	0.0170 (3)
C5	0.76778 (10)	0.7588 (3)	0.61399 (9)	0.0182 (3)
C6	0.86115 (10)	0.6839 (3)	0.61053 (9)	0.0200 (3)
C7	0.93157 (10)	0.8105 (4)	0.56164 (10)	0.0275 (4)
H7A	0.9917	0.7674	0.5844	0.041*
H7B	0.9232	1.0128	0.5598	0.041*
H7C	0.9261	0.7346	0.5085	0.041*
C8	0.80259 (10)	0.2105 (3)	0.75710 (9)	0.0188 (3)
C9	0.88429 (10)	0.0839 (3)	0.77948 (10)	0.0246 (4)
H9	0.9388	0.1388	0.7562	0.030*
C10	0.88520 (11)	−0.1224 (4)	0.83593 (10)	0.0291 (4)
H10	0.9408	−0.2087	0.8512	0.035*
C11	0.80605 (12)	−0.2052 (3)	0.87057 (10)	0.0281 (4)
H11	0.8072	−0.3483	0.9089	0.034*
C12	0.72548 (11)	−0.0761 (3)	0.84836 (9)	0.0257 (4)
H12	0.6710	−0.1311	0.8718	0.031*
C13	0.72332 (10)	0.1325 (3)	0.79237 (9)	0.0223 (3)
H13	0.6678	0.2218	0.7782	0.027*
H2B	0.4722 (14)	0.939 (4)	0.6543 (13)	0.036 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0188 (5)	0.0262 (6)	0.0333 (6)	0.0053 (4)	0.0009 (5)	0.0035 (5)
N1	0.0220 (6)	0.0268 (7)	0.0289 (7)	0.0044 (6)	0.0004 (5)	0.0080 (6)
N2	0.0169 (6)	0.0288 (7)	0.0338 (8)	0.0048 (6)	0.0065 (6)	0.0094 (6)
N3	0.0142 (6)	0.0202 (6)	0.0219 (6)	0.0006 (5)	0.0015 (5)	−0.0010 (5)
N4	0.0156 (6)	0.0200 (6)	0.0201 (6)	−0.0005 (5)	−0.0004 (5)	−0.0020 (5)
N5	0.0135 (6)	0.0255 (7)	0.0221 (6)	0.0001 (5)	0.0024 (5)	−0.0011 (5)
N6	0.0133 (6)	0.0205 (6)	0.0216 (6)	0.0010 (5)	0.0012 (5)	0.0010 (5)
C1	0.0191 (7)	0.0182 (7)	0.0229 (7)	0.0009 (6)	−0.0021 (6)	−0.0029 (6)
C2	0.0171 (7)	0.0182 (7)	0.0208 (7)	0.0000 (6)	−0.0005 (6)	−0.0021 (6)
C3	0.0155 (7)	0.0195 (7)	0.0218 (7)	−0.0002 (5)	0.0004 (6)	−0.0034 (6)
C4	0.0157 (7)	0.0175 (7)	0.0177 (7)	0.0002 (5)	−0.0006 (5)	−0.0027 (5)
C5	0.0151 (7)	0.0195 (7)	0.0201 (7)	−0.0003 (5)	0.0013 (5)	−0.0016 (6)
C6	0.0151 (7)	0.0238 (7)	0.0212 (7)	0.0001 (6)	0.0011 (6)	−0.0012 (6)
C7	0.0177 (7)	0.0356 (9)	0.0295 (8)	0.0003 (6)	0.0049 (6)	0.0057 (7)
C8	0.0185 (7)	0.0183 (7)	0.0195 (7)	0.0008 (6)	−0.0006 (6)	−0.0016 (6)
C9	0.0173 (7)	0.0285 (8)	0.0280 (8)	0.0019 (6)	−0.0007 (6)	0.0017 (7)
C10	0.0236 (8)	0.0312 (8)	0.0319 (9)	0.0038 (7)	−0.0052 (7)	0.0048 (7)
C11	0.0335 (9)	0.0270 (8)	0.0236 (8)	−0.0014 (7)	−0.0025 (7)	0.0039 (7)
C12	0.0262 (8)	0.0277 (8)	0.0235 (8)	−0.0044 (7)	0.0045 (6)	−0.0007 (6)
C13	0.0179 (7)	0.0243 (7)	0.0248 (8)	0.0004 (6)	0.0016 (6)	−0.0004 (6)

Geometric parameters (Å, º) top

O1—C1	1.2444 (18)	C4—C5	1.407 (2)
N1—H1A	0.8800	C5—C6	1.430 (2)
N1—H1B	0.8800	C6—C7	1.489 (2)
N1—C1	1.329 (2)	C7—H7A	0.9800
N2—H2A	0.8636	C7—H7B	0.9800
N2—C3	1.3509 (19)	C7—H7C	0.9800
N2—H2B	0.93 (2)	C8—C9	1.394 (2)
N3—C3	1.340 (2)	C8—C13	1.389 (2)
N3—C4	1.3341 (18)	C9—H9	0.9500
N4—C2	1.3316 (19)	C9—C10	1.384 (2)
N4—C5	1.338 (2)	C10—H10	0.9500
N5—N6	1.3927 (16)	C10—C11	1.389 (2)
N5—C6	1.314 (2)	C11—H11	0.9500
N6—C4	1.3656 (19)	C11—C12	1.384 (2)
N6—C8	1.4193 (19)	C12—H12	0.9500
C1—C2	1.497 (2)	C12—C13	1.386 (2)
C2—C3	1.446 (2)	C13—H13	0.9500

H1A—N1—H1B	120.0	N5—C6—C5	110.00 (13)
C1—N1—H1A	120.0	N5—C6—C7	121.93 (13)
C1—N1—H1B	120.0	C5—C6—C7	128.05 (14)
H2A—N2—H2B	127.9	C6—C7—H7A	109.5
C3—N2—H2A	110.1	C6—C7—H7B	109.5
C3—N2—H2B	117.8 (13)	C6—C7—H7C	109.5
C4—N3—C3	113.86 (12)	H7A—C7—H7B	109.5
C2—N4—C5	115.77 (12)	H7A—C7—H7C	109.5
C6—N5—N6	107.54 (12)	H7B—C7—H7C	109.5
N5—N6—C8	119.49 (12)	C9—C8—N6	119.68 (14)
C4—N6—N5	110.22 (12)	C13—C8—N6	120.33 (13)
C4—N6—C8	130.23 (13)	C13—C8—C9	119.98 (14)
O1—C1—N1	122.47 (14)	C8—C9—H9	120.3
O1—C1—C2	121.81 (14)	C10—C9—C8	119.38 (15)
N1—C1—C2	115.72 (13)	C10—C9—H9	120.3
N4—C2—C1	116.34 (13)	C9—C10—H10	119.5
N4—C2—C3	121.88 (13)	C9—C10—C11	121.07 (15)
C3—C2—C1	121.78 (13)	C11—C10—H10	119.5
N2—C3—C2	121.43 (13)	C10—C11—H11	120.5
N3—C3—N2	116.29 (13)	C12—C11—C10	118.98 (15)
N3—C3—C2	122.25 (13)	C12—C11—H11	120.5
N3—C4—N6	128.75 (13)	C11—C12—H12	119.6
N3—C4—C5	124.66 (13)	C11—C12—C13	120.79 (15)
N6—C4—C5	106.58 (13)	C13—C12—H12	119.6
N4—C5—C4	121.50 (13)	C8—C13—H13	120.1
N4—C5—C6	132.81 (14)	C12—C13—C8	119.78 (15)
C4—C5—C6	105.66 (13)	C12—C13—H13	120.1

O1—C1—C2—N4	−179.29 (13)	C2—N4—C5—C4	0.8 (2)
O1—C1—C2—C3	0.3 (2)	C2—N4—C5—C6	−176.75 (15)
N1—C1—C2—N4	0.6 (2)	C3—N3—C4—N6	176.55 (14)
N1—C1—C2—C3	−179.82 (13)	C3—N3—C4—C5	−2.4 (2)
N3—C4—C5—N4	0.4 (2)	C4—N3—C3—N2	−174.80 (13)
N3—C4—C5—C6	178.55 (13)	C4—N3—C3—C2	3.3 (2)
N4—C2—C3—N2	175.69 (14)	C4—N6—C8—C9	−173.91 (14)
N4—C2—C3—N3	−2.3 (2)	C4—N6—C8—C13	6.5 (2)
N4—C5—C6—N5	178.32 (15)	C4—C5—C6—N5	0.45 (17)
N4—C5—C6—C7	0.1 (3)	C4—C5—C6—C7	−177.76 (15)
N5—N6—C4—N3	−178.54 (13)	C5—N4—C2—C1	179.62 (12)
N5—N6—C4—C5	0.58 (16)	C5—N4—C2—C3	0.0 (2)
N5—N6—C8—C9	3.0 (2)	C6—N5—N6—C4	−0.30 (16)
N5—N6—C8—C13	−176.51 (13)	C6—N5—N6—C8	−177.82 (13)
N6—N5—C6—C5	−0.10 (16)	C8—N6—C4—N3	−1.4 (3)
N6—N5—C6—C7	178.24 (13)	C8—N6—C4—C5	177.75 (14)
N6—C4—C5—N4	−178.78 (13)	C8—C9—C10—C11	0.0 (3)
N6—C4—C5—C6	−0.61 (16)	C9—C8—C13—C12	−1.6 (2)
N6—C8—C9—C10	−178.44 (15)	C9—C10—C11—C12	−0.6 (3)
N6—C8—C13—C12	177.92 (14)	C10—C11—C12—C13	0.1 (2)
C1—C2—C3—N2	−3.9 (2)	C11—C12—C13—C8	1.0 (2)
C1—C2—C3—N3	178.17 (13)	C13—C8—C9—C10	1.1 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2B···O1	0.93 (2)	1.97 (2)	2.6878 (18)	132.1 (17)
C13—H13···N3	0.95	2.31	2.985 (2)	127
N1—H1A···O1ⁱ	0.88	2.07	2.9488 (18)	175
N2—H2A···N2ⁱⁱ	0.86	2.50	3.345 (2)	167

Symmetry codes: (i) −x+1, −y+3, −z+1; (ii) −x+1, y−1/2, −z+3/2.

Acknowledgements

JPJ would like to acknowledge the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

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