5,6-Dimethyl-4-(thio­phen-2-yl)-1H-pyrazolo­[3,4-b]pyridin-3-amine

Hatem A Abdel-Aziz; Khalid A Al-Rashood; Hazem A Ghabbour; Suchada Chantrapromma; Hoong-Kun Fun

doi:10.1107/S1600536812004126

. 2012 Feb 4;68(Pt 3):o612–o613. doi: 10.1107/S1600536812004126

5,6-Dimethyl-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

Hatem A Abdel-Aziz ^a, Khalid A Al-Rashood ^a, Hazem A Ghabbour ^a, Suchada Chantrapromma ^b,^‡, Hoong-Kun Fun ^c,^*,^§

PMCID: PMC3295413 PMID: 22412524

Abstract

In the title molecule, C₁₂H₁₂N₄S, the thiophene ring is disordered over two orientations with a refined site-occupancy ratio of 0.777 (4):0.223 (4). The pyrazolopyridine ring system is essentially planar with an r.m.s. deviation of 0.0069 (3) Å and makes dihedral angles of 82.8 (2) and 72.6 (5)°, respectively, with the major and minor components of the thiophene ring. In the crystal, molecules are linked into a chain along the a axis by a pair of N—H⋯N(pyrazole) hydrogen bonds and a pair of N—H⋯N(pyridine) hydrogen bonds, both having a centrosymmetric R ₂ ²(8) graph-set motif. A C—H⋯π interaction is also present.

Related literature

For bond-length data, see: Allen et al. (1987 ▶). For details of hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For background to and bioactivity of pyrazole derivatives, see: Ali (2009 ▶); Bharate et al. (2008 ▶); Fu et al. (2010 ▶); Thumar & Patel (2011 ▶). For a related structure, see: Fun et al. (2011 ▶).

Experimental

Crystal data

C₁₂H₁₂N₄S
M _r = 244.33
Monoclinic,
a = 10.0688 (2) Å
b = 8.0116 (2) Å
c = 15.7479 (3) Å
β = 106.809 (1)°
V = 1216.06 (5) Å³
Z = 4
Cu Kα radiation
μ = 2.22 mm⁻¹
T = 296 K
0.44 × 0.33 × 0.14 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.445, T _max = 0.746
15551 measured reflections
2379 independent reflections
2073 reflections with I > 2σ(I)
R _int = 0.040

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.139
S = 1.05
2379 reflections
185 parameters
8 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.46 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812004126/is5063sup1.cif

e-68-0o612-sup1.cif^{(25.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812004126/is5063Isup2.hkl

e-68-0o612-Isup2.hkl^{(116.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812004126/is5063Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the C1–C3/N1/C5/C6 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯N1ⁱ	0.86	2.08	2.937 (2)	171
N4—H1N4⋯N3ⁱⁱ	0.93 (2)	2.13 (2)	3.056 (3)	176 (2)
C12—H12B⋯Cg1ⁱⁱⁱ	0.96	2.94	3.717 (2)	139

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

Acknowledgments

The authors thank King Saud University and the Universiti Sains Malaysia for the Research University grant No. 1001/PFIZIK/811160. HKF thanks the King Saud University, Riyadn, Saudi Arabia, for the award of a visiting professorship (23 December 2011 to 14 January 2012). The authors also thank the Deanship of Scientific Research and Research Center, College of Pharmacy, King Saud University.

supplementary crystallographic information

Comment

The synthesis of pyrazole derivatives have attracted a lot of interests in medicinal chemistry owing to their biological properties such as anti-cancer (Fu et al., 2010), anti-inflammatory (Bharate et al., 2008) and antimicrobial activities (Ali, 2009; Thumar & Patel, 2011). Pyrazolopyridine, a fused heterocycle, is of interest as a component of potential bioactive molecules. Our on-going research on biological activity of pyrazolone Schiff bases led us to synthesize the title compound (I). Herein, its crystal structure was reported.

In the molecule, C₁₂H₁₂N₄S, the thiophene ring is disordered over two positions with the refined site-occupancy ratio of 0.777 (4):0.223 (4). The pyrazolo[3,4-b]pyridine moiety (C1–C6/N1–N3) is planar with an r.m.s. deviation of 0.0069 (3) Å and the dihedral angle between the pyrazole and pyridine rings is 1.16 (9)°. This planar unit makes dihedral angles of 82.8 (2) and 77.6 (5)° with the major and minor components of the thiophene rings, respectively. The amine and two methyl substituents are co-planar with the pyrazolo[3,4-b]pyridine with an r.m.s. deviation of 0.0122 (3) Å for the 12 non-H atoms (C1–C6/N1–N4/C11-C12). The bond distances in (I) are within normal ranges (Allen et al., 1987) and comparable to the related structure (Fun et al., 2011).

In the crystal packing, (Fig. 2), the molecules are linked by N2—H2A···N1 and N4—H1N4···N3 hydrogen bonds (Table 1) into cyclic centrosymmetric R²₂(8) dimers (Bernstein et al., 1995). These dimers are linked into a chain along the a axis (Fig. 2). A weak C—H···π interaction is also observed (Table 1).

Experimental

A mixture of 2-chloro-5,6-dimethyl-4-(thiophen-2-yl)nicotinonitrile (0.248 g, 1 mmol) and hydrazine hydrate (0.5 mL, 99%) in absolute ethanol (20 ml) was refluxed for 16 h. The reaction mixture was cooled and poured onto ice/water mixture. The precipitate that formed was filtered off, washed with water, dried and crystallized from EtOH/DMF to give yellow crystals of the title compound in 69% yield. Orange block-shaped single crystals of the title compound suitable for X-ray structure determination were recrystallized from ETOH/DMF (3:1 v/v) by the slow evaporation of the solvent at room temperature after several days.