3-Amino-4,6-dimethyl­thieno[2,3-b]pyridine-2-carbonitrile

Zeng, X.-X.; Ye, T.-H.; Lun, D.-W.; Yu, L.-T.; Yang, L.

doi:10.1107/S1600536809048132

organic compounds

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ISSN: 2056-9890

Volume 65| Part 12| December 2009| Page o3138

doi:10.1107/S1600536809048132

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3-Amino-4,6-dimethylthieno[2,3-b]pyridine-2-carbonitrile

Xiu-Xiu Zeng,^a Ting-Hong Ye,^b Dong-Wen Lun,^a Luo-Ting Yu ^b and Li Yang ^b ^*

^aDepartment of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, People's Republic of China, and ^bState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China
^*Correspondence e-mail: yangli@scu.edu.cn

(Received 5 November 2009; accepted 13 November 2009; online 21 November 2009)

The molecule of the title compound, C₁₀H₉N₃S, is almost planar, with a dihedral angle of 1.38 (4)° between the thiophene and pyridine rings. In the crystal packing, molecules are linked into layers parallel to the ab plane by intermolecular N—H⋯N hydrogen bonds and by π⋯π stacking interactions involving adjacent pyridine and thiophene rings with a centroid–centroid distance of 3.537 (3) Å.

Related literature

For the biological properties of thieno[2,3-b]pyridine derivatives, see: Litvinov et al. (2005 ).

Experimental

Crystal data

C₁₀H₉N₃S
M_r = 203.26
Orthorhombic, P b c a
a = 14.562 (3) Å
b = 8.1252 (16) Å
c = 16.211 (3) Å
V = 1918.1 (7) Å³
Z = 8
Mo Kα radiation
μ = 0.30 mm⁻¹
T = 113 K
0.26 × 0.25 × 0.20 mm

Data collection

Rigaku Saturn CCD area detector diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ) T_min = 0.927, T_max = 0.943
16095 measured reflections
2280 independent reflections
2047 reflections with I > 2σ(I)
R_int = 0.038

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.101
S = 1.04
2280 reflections
137 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N⋯N1ⁱ	0.881 (19)	2.180 (19)	3.0361 (17)	163.9 (17)
N2—H2N⋯N3ⁱⁱ	0.89 (2)	2.35 (2)	3.0900 (18)	141.1 (16)
Symmetry codes: (i) $[x+{\script{1\over 2}}, y, -z+{\script{3\over 2}}]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: CrystalClear (Rigaku/MSC,2005 ); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ); software used to prepare material for publication: PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablock I. DOI: 10.1107/S1600536809048132/rz2391sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809048132/rz2391Isup2.hkl

checkCIF report

Comment top

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 research aimed at the synthesis and investigation of new antitumor drugs. We report here its crystal structure.

The thieno[2,3-b]pyridine ring system of the title molecule (Fig. 1) is almost planar, the dihedral angle formed by the thiophene and pyridine rings being 1.38 (4)°. The N2 amine atom, the C8/N3 nitrile atoms and the C9/C10 methyl atoms are displaced from the mean plane through the dimethylthieno[2,3-b]pyridine ring system by 0.0761 (13), 0.0478 (14), 0.0922 (13), 0.0934 (15) and 0.0680 (15) Å, respectively. In the crystal structure (Fig. 2), the molecules are linked into layers parallel to the ab plane by intermolecular N—H···N hydrogen bonds (Table 1) and by π···π stacking interactions involving adjacent pyridine and thiophene rings, with a centroid-to-centroid distance of 3.537 (3) Å.

Related literature top

For the biological properties of thieno[2,3-b]pyridine derivatives, see: Litvinov et al. (2005).

Experimental top

To a suspension of 4,6-dimethyl-3-cyanopyridine-2-(1H)-thione (1.7 g, 10 mmol) in DMF (20 ml) was added a 10% aqueous KOH solution (5.6 ml,10 mmol) followed by the addition of chloroacetonitrile (0.8 g, 10 mmol) at room temperature. After stirring for 10–15 min at r.t., a 10% aqueous KOH solution (5.6 ml,10 mmol) was added and the mixture heated to 358 K for 6 h. The reaction mixture was then allowed to cool to r.t., the precipitate was collected by filtration and washed with cold ethanol, then it was recrystallized from ethanol to give a white solid (1.6 g, 80% yield). Crystals suitable for X-ray analysis were obtained by slow evaporation of a methanol/dichloromethane (1:2 v/v) solution.

Computing details top

Data collection: CrystalClear (Rigaku/MSC,2005); cell refinement: CrystalClear (Rigaku/MSC,2005); data reduction: CrystalClear (Rigaku/MSC,2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. Packing diagram of the title compound. Hydrogen bonds are shown as dotted lines.

3-amino-4,6-dimethylthieno[2,3-b]pyridine-2-carbonitrile top

Crystal data top

C₁₀H₉N₃S	F(000) = 848
M_r = 203.26	D_x = 1.408 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 5470 reflections
a = 14.562 (3) Å	θ = 2.5–27.9°
b = 8.1252 (16) Å	µ = 0.30 mm⁻¹
c = 16.211 (3) Å	T = 113 K
V = 1918.1 (7) Å³	Block, colourless
Z = 8	0.26 × 0.25 × 0.20 mm

Data collection top

Rigaku Saturn CCD area detector diffractometer	2280 independent reflections
Radiation source: rotating anode	2047 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.038
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 3.1°
ω and ϕ scans	h = −19→18
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −10→8
T_min = 0.927, T_max = 0.943	l = −21→21
16095 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.037	Hydrogen site location: mixed
wR(F²) = 0.101	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.0627P)² + 0.6561P] where P = (F_o² + 2F_c²)/3
2280 reflections	(Δ/σ)_max = 0.001
137 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.34 e Å⁻³

Crystal data top

C₁₀H₉N₃S	V = 1918.1 (7) Å³
M_r = 203.26	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 14.562 (3) Å	µ = 0.30 mm⁻¹
b = 8.1252 (16) Å	T = 113 K
c = 16.211 (3) Å	0.26 × 0.25 × 0.20 mm

Data collection top

Rigaku Saturn CCD area detector diffractometer	2280 independent reflections
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	2047 reflections with I > 2σ(I)
T_min = 0.927, T_max = 0.943	R_int = 0.038
16095 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.101	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	Δρ_max = 0.33 e Å⁻³
2280 reflections	Δρ_min = −0.34 e Å⁻³
137 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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.

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

	x	y	z	U_iso*/U_eq
S1	0.20101 (2)	0.66501 (4)	0.69746 (2)	0.01744 (13)
N1	0.09825 (8)	0.51450 (14)	0.81134 (7)	0.0168 (3)
N2	0.43428 (8)	0.53762 (16)	0.80376 (7)	0.0197 (3)
H1N	0.4779 (13)	0.550 (2)	0.7666 (11)	0.030 (5)*
H2N	0.4479 (13)	0.463 (2)	0.8416 (12)	0.032 (5)*
N3	0.42910 (9)	0.79977 (16)	0.61222 (7)	0.0231 (3)
C1	0.09139 (9)	0.42573 (17)	0.88087 (8)	0.0175 (3)
C2	0.16908 (9)	0.37944 (17)	0.92658 (8)	0.0179 (3)
H2	0.1608	0.3189	0.9762	0.021*
C3	0.25762 (9)	0.41919 (17)	0.90166 (8)	0.0163 (3)
C4	0.26566 (9)	0.50818 (16)	0.82730 (8)	0.0150 (3)
C5	0.34563 (9)	0.56490 (16)	0.78168 (8)	0.0154 (3)
C6	0.31997 (10)	0.65374 (17)	0.71273 (9)	0.0170 (3)
C7	0.18349 (9)	0.55260 (17)	0.78720 (8)	0.0151 (3)
C8	0.38019 (9)	0.73372 (17)	0.65747 (8)	0.0175 (3)
C9	−0.00311 (9)	0.37597 (18)	0.90758 (9)	0.0222 (3)
H9A	−0.0352	0.4716	0.9305	0.033*
H9B	0.0013	0.2899	0.9497	0.033*
H9C	−0.0373	0.3338	0.8600	0.033*
C10	0.33843 (10)	0.36632 (19)	0.95308 (8)	0.0225 (3)
H10A	0.3165	0.3099	1.0027	0.034*
H10B	0.3743	0.4633	0.9690	0.034*
H10C	0.3772	0.2913	0.9210	0.034*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0131 (2)	0.0222 (2)	0.0170 (2)	0.00032 (12)	−0.00226 (11)	0.00211 (12)
N1	0.0128 (6)	0.0185 (6)	0.0190 (5)	0.0002 (4)	0.0006 (4)	−0.0026 (4)
N2	0.0116 (6)	0.0276 (7)	0.0198 (6)	0.0016 (5)	0.0007 (4)	0.0031 (5)
N3	0.0209 (6)	0.0269 (7)	0.0217 (6)	−0.0034 (5)	0.0009 (5)	0.0004 (5)
C1	0.0153 (7)	0.0178 (6)	0.0194 (6)	−0.0003 (5)	0.0022 (5)	−0.0038 (5)
C2	0.0175 (7)	0.0198 (7)	0.0165 (6)	0.0004 (5)	0.0025 (5)	−0.0011 (5)
C3	0.0154 (6)	0.0175 (6)	0.0159 (6)	0.0016 (5)	−0.0006 (5)	−0.0035 (5)
C4	0.0127 (6)	0.0158 (6)	0.0165 (6)	0.0001 (5)	0.0000 (5)	−0.0032 (5)
C5	0.0129 (6)	0.0166 (6)	0.0166 (6)	0.0003 (5)	−0.0008 (5)	−0.0031 (5)
C6	0.0131 (6)	0.0201 (7)	0.0178 (6)	−0.0005 (5)	−0.0003 (5)	−0.0011 (5)
C7	0.0140 (6)	0.0155 (6)	0.0157 (6)	0.0004 (5)	−0.0012 (5)	−0.0023 (5)
C8	0.0156 (6)	0.0194 (6)	0.0175 (6)	0.0004 (5)	−0.0026 (5)	−0.0019 (5)
C9	0.0141 (7)	0.0269 (8)	0.0255 (7)	−0.0019 (5)	0.0028 (5)	−0.0012 (6)
C10	0.0180 (7)	0.0316 (8)	0.0179 (6)	0.0027 (6)	−0.0012 (5)	0.0037 (6)

Geometric parameters (Å, º) top

S1—C7	1.7366 (14)	C3—C4	1.4104 (18)
S1—C6	1.7522 (15)	C3—C10	1.5047 (19)
N1—C7	1.3377 (17)	C4—C7	1.4088 (18)
N1—C1	1.3419 (17)	C4—C5	1.4546 (18)
N2—C5	1.3579 (17)	C5—C6	1.3820 (19)
N2—H1N	0.881 (19)	C6—C8	1.4121 (19)
N2—H2N	0.89 (2)	C9—H9A	0.9800
N3—C8	1.1547 (18)	C9—H9B	0.9800
C1—C2	1.4038 (19)	C9—H9C	0.9800
C1—C9	1.4982 (18)	C10—H10A	0.9800
C2—C3	1.3892 (19)	C10—H10B	0.9800
C2—H2	0.9500	C10—H10C	0.9800

C7—S1—C6	89.97 (7)	C5—C6—C8	125.84 (13)
C7—N1—C1	116.05 (11)	C5—C6—S1	114.14 (10)
C5—N2—H1N	119.1 (12)	C8—C6—S1	120.02 (11)
C5—N2—H2N	120.5 (12)	N1—C7—C4	126.42 (12)
H1N—N2—H2N	112.9 (16)	N1—C7—S1	120.21 (10)
N1—C1—C2	121.83 (12)	C4—C7—S1	113.36 (10)
N1—C1—C9	117.14 (12)	N3—C8—C6	179.64 (15)
C2—C1—C9	121.03 (12)	C1—C9—H9A	109.5
C3—C2—C1	122.15 (13)	C1—C9—H9B	109.5
C3—C2—H2	118.9	H9A—C9—H9B	109.5
C1—C2—H2	118.9	C1—C9—H9C	109.5
C2—C3—C4	116.41 (12)	H9A—C9—H9C	109.5
C2—C3—C10	119.88 (12)	H9B—C9—H9C	109.5
C4—C3—C10	123.71 (12)	C3—C10—H10A	109.5
C7—C4—C3	117.08 (12)	C3—C10—H10B	109.5
C7—C4—C5	111.36 (12)	H10A—C10—H10B	109.5
C3—C4—C5	131.56 (12)	C3—C10—H10C	109.5
N2—C5—C6	123.75 (13)	H10A—C10—H10C	109.5
N2—C5—C4	125.13 (12)	H10B—C10—H10C	109.5
C6—C5—C4	111.11 (12)

C7—N1—C1—C2	1.59 (19)	N2—C5—C6—C8	−2.6 (2)
C7—N1—C1—C9	−177.76 (12)	C4—C5—C6—C8	176.41 (13)
N1—C1—C2—C3	−1.6 (2)	N2—C5—C6—S1	178.35 (11)
C9—C1—C2—C3	177.76 (13)	C4—C5—C6—S1	−2.65 (15)
C1—C2—C3—C4	−0.4 (2)	C7—S1—C6—C5	1.57 (11)
C1—C2—C3—C10	−179.98 (13)	C7—S1—C6—C8	−177.55 (12)
C2—C3—C4—C7	2.05 (18)	C1—N1—C7—C4	0.3 (2)
C10—C3—C4—C7	−178.37 (12)	C1—N1—C7—S1	179.24 (10)
C2—C3—C4—C5	−177.59 (13)	C3—C4—C7—N1	−2.2 (2)
C10—C3—C4—C5	2.0 (2)	C5—C4—C7—N1	177.56 (13)
C7—C4—C5—N2	−178.43 (13)	C3—C4—C7—S1	178.83 (10)
C3—C4—C5—N2	1.2 (2)	C5—C4—C7—S1	−1.46 (15)
C7—C4—C5—C6	2.60 (16)	C6—S1—C7—N1	−179.09 (12)
C3—C4—C5—C6	−177.75 (14)	C6—S1—C7—C4	0.00 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1N···N1ⁱ	0.881 (19)	2.180 (19)	3.0361 (17)	163.9 (17)
N2—H2N···N3ⁱⁱ	0.89 (2)	2.35 (2)	3.0900 (18)	141.1 (16)

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

Experimental details

Crystal data
Chemical formula	C₁₀H₉N₃S
M_r	203.26
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	113
a, b, c (Å)	14.562 (3), 8.1252 (16), 16.211 (3)
V (Å³)	1918.1 (7)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.30
Crystal size (mm)	0.26 × 0.25 × 0.20

Data collection
Diffractometer	Rigaku Saturn CCD area detector diffractometer
Absorption correction	Multi-scan (ABSCOR; Higashi, 1995)
T_min, T_max	0.927, 0.943
No. of measured, independent and observed [I > 2σ(I)] reflections	16095, 2280, 2047
R_int	0.038
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.101, 1.04
No. of reflections	2280
No. of parameters	137
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.34

Computer programs: CrystalClear (Rigaku/MSC,2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEPIII (Burnett & Johnson, 1996), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1N···N1ⁱ	0.881 (19)	2.180 (19)	3.0361 (17)	163.9 (17)
N2—H2N···N3ⁱⁱ	0.89 (2)	2.35 (2)	3.0900 (18)	141.1 (16)

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

Acknowledgements

The project was sponsored by the Scientific Research Foundation for Returned Overseas Chinese Scholars (No. 20071108–18-14), State Education Ministry. We thank the Analytical and Testing Center of Sichuan University for the X-ray measurements.

References

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