3-Amino-N-benzyl-6-(4-fluoro­phen­yl)thieno[2,3-b]pyridine-2-carboxamide

Jin-Ni Zhao; Sheng-Yong Yang; Li Yang

doi:10.1107/S160053681202212X

. 2012 May 19;68(Pt 6):o1823. doi: 10.1107/S160053681202212X

3-Amino-N-benzyl-6-(4-fluorophenyl)thieno[2,3-b]pyridine-2-carboxamide

Jin-Ni Zhao ^a, Sheng-Yong Yang ^a, Li Yang ^a,^*

PMCID: PMC3379397 PMID: 22719595

Abstract

In the title compound, C₂₁H₁₆FN₃OS, the thieno[2,3-b]pyridine system forms dihedral angles of 10.57 (12) and 83.87 (5)° with the fluorophenyl ring at the 6-position and the phenyl ring of the benzyl group, respectively. In the crystal, molecules are linked by weak N—H⋯N anf N—H⋯O hydrogen bonds and π–π stacking interactions involving fluorophenyl rings of adjacent molecules, with a centroid–centroid distance of 3.648 (10) Å. In addition, intramolecular N—H⋯S and N—H⋯O hydrogen bonds contribute to the stability of the molecular conformation.

Related literature

For the biological activity of thieno[2,3-b]pyridine derivatives, see: Litvinov et al. (2005 ▶). graphic file with name e-68-o1823-scheme1.jpg

Experimental

Crystal data

C₂₁H₁₆FN₃OS
M _r = 377.43
Monoclinic,
a = 18.9008 (7) Å
b = 9.9828 (4) Å
c = 9.5924 (4) Å
β = 102.224 (4)°
V = 1768.89 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.40 × 0.30 × 0.10 mm

Data collection

Oxford Diffraction Xcalibur Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2006 ▶) T _min = 0.991, T _max = 1.000
7919 measured reflections
3609 independent reflections
2665 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.104
S = 1.03
3609 reflections
252 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: OLEX2.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681202212X/ds2191sup1.cif

e-68-o1823-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681202212X/ds2191Isup2.hkl

e-68-o1823-Isup2.hkl^{(177KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681202212X/ds2191Isup3.cml

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯S1	0.86	2.68	3.0897 (16)	111
N3—H3⋯N2ⁱ	0.86	2.51	3.253 (2)	146
N2—H2B⋯O1	0.90 (2)	2.15 (2)	2.741 (2)	122.7 (17)
N2—H2B⋯O1ⁱⁱ	0.90 (2)	2.20 (2)	3.015 (2)	150.0 (17)

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

Acknowledgments

We thank the Analytical and Testing Center of Sichuan University for the X-ray measurements.

supplementary crystallographic information

Comment

Thieno[2,3-b]pyridine derivatives are of great importance owing to their wide biological properties (Litvinov et al., 2005). The title compound is one of the key intermediates in our synthetic investigations of anticancer drugs. Herein we report its crystal structure.

As shown in Fig. 1, the thieno[2,3-b]pyridine ring forms dihedral angles of 10.57(0.12)° and 83.87(0.05)° with the monofluoro-benzene at 6-position and the phenyl rings at 2-position, respectively.In the crystal packing, stacking interactions involving phenyl rings containing fluorine atom of adjacent molecules are helpful for the stabilization of the crystal as well as intermolecular N—H···N hydrogen bonds.In addition,intramolecular N—H···O and N—H···S hydrogen bonds help to stabilize the molecular conformation (Table 1 and Fig.2).

Experimental

To a solution of 6-(4-fluorophenyl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile (2.30 g, 10 mmol) in DMF (15.00 ml) was added dropwise a solution of 10% sodium hydroxide (8.00 ml). After stirring at room temperature for 0.5 h and then the temperature was raised to 85 °C and then 10% sodium hydroxide (8.00 ml) and N-benzyl-2-chloroacetamide (2.20 g, 12.0 mmol) were added. The reaction mixture was stirred under reflux until complete conversion of the starting materials (6 h, monitored by TLC). The mixture was then cooled to room temperature and crystallized to give 3.17 g of an yellow solid (84% yield).The product was recrystallized from ethanol to afford the title compound as an off-yellow solid (yield: 60%). Crystals suitable for X-ray analysis were obtained by slow evaporation using dichloromethane methanol (2:1 v/v) as eluent.