Ethyl 3-amino-6-phenyl-4-tolylthieno[2,3-b]pyridine-2-carboxylate

In the title compound, C₂₃H₂₀N₂O₂S, the central thieno­pyridine ring system is essentially planar, the dihedral angle between the planes of the two rings being 0.3 (2)°. The terminal ethyl carboxyl­ate group is twisted by 26.7 (3)° away from the central ring system. A short intramolecular hydrogen bond involving the amino N atom and the carbonyl O atom [N...O = 2.806 (4) Å] forms a pseudo-six-membered ring. Significant intermolecular C—H...N, C—H...O and C—H...π interactions contribute strongly to the stability of the structure, along with weak π–π-stacking interactions.

S1. Comment

Thienopyridines are bicyclic heterocycles in which a thiophene ring is fused to a pyridine ring. Being isoesters of classical quinolines (Friedrichsen, 1984), these compounds show a wide range of pharmaceutical activities, such as antihypertensive (Davis & Fraser, 1987), antimicrobial (Gills et al., 1980) and antiulcer (Briel, 1998) properties. In continuation of our recent studies of the 2-pyridine class of compounds (Patel et al., 2002) to investigate the influence of different substituents upon the structural parameters of the molecule, we report here the crystal and molecular structure of a fused system of a π-deficient pyridine ring and a π-rich thiophene ring, the title compound, (I). \sch

Fig. 1 shows the molecular structure of (I). The molecular dimensions of the thienopyridine ring system are normal, except for a slight deviation observed in the endocyclic angle at C1 of the pyridine ring; the C2—C1—N1 angle is enlarged to 126.7 (3)° (Kvick & Noordik, 1977). The C1—N1—C5 angle of 116.3 (2)° is as expected for a non-protonated ring system, being smaller than 120° (Ghosh & Simonsen, 1993). The C—S bonds [1.739 (3) and 1.742 (3) Å] of the thiophene ring are long compared with the values observed in the free thiophene structure, measured using electron diffraction (1.714 Å; Bonham & Momany, 1963), and in thieno[2,3-c]pyridine [1.728 (1) and 1.731 (1) Å; Nerenz et al., 1997]. The corresponding values in the non-fused system, 2-(2-thienyl)pyridine (Ghosh & Simonsen, 1993), are 1.712 (3) and 1.723 (3) Å to the substituted and non-substituted C atoms, respectively. The C—S—C angle of 90.1 (2)° in (I) is comparable with that observed in thieno[2,3-c]pyridine, but is slightly less than that observed in free thiophene [92.2 (2)°]. In general, the molecular dimensions of the fused ring system of (I) agree well with the corresponding values of other similar compounds (Nerenz et al., 1997).

The O-Csp² bond of the terminal ester group in (I) [1.360 (4) Å] is higher than the normal value but agrees well with the values found in other compounds containing this molecular fragment (Csöregh & Palm, 1977). The unusual C22—C23 bond distance [1.401 (7) Å] can probably be attributed to non-resolved disorder of the methyl terminus, as indicated by the unusual displacement parameters for atoms C22 and C23.

The C20—C21—O2—C22 torsional angle of 175.5 (4)° describes the trans configuration of the molecule about the C21—O2 bond. The central thienopyridine ring system is planar, the dihedral angle between these ring planes being 0.3 (2)°. Both phenyl rings are planar within themselves, with maximum deviations of 0.0035 and 0.0054 Å For which atoms? from their respective mean planes. However, the participation of two atoms (C10 and C11) of the phenyl ring at C3 in strong intermolecular interactions with the NH₂ group at C19 (see below) rotates the ring markedly, by 69.9 (1)° out of central ring system, whereas in the absence of any such interactions, the phenyl ring at C5 is almost coplanar with the central ring system [dihedral angle 5.2 (2)°].

The terminal ester group is twisted substantially out of the central ring system [dihedral angle 26.7 (3)°]. The carbonyl moiety is coplanar with the thiophene ring and has a cis orientation, characterized by the C19—C20—C21—O1 torsion angle of 1.1 (6)°, thereby placing the amino atom N2 in strong intramolecular contact with carbonyl atom O1 [N2—H2A···O1 2.806 (4) Å, H2A···O1 2.2 Å and N2—H2A···O1 128°] and forming a pseudo six-membered ring.

A network of intermolecular C—H···N and C—H···O interactions (Fig. 2.), as well as C—H···π and π–π interactions, provide a strong packing to the structure of (I). Phenyl ring atoms C10 and C11 are hydrogen bonded to atom N1 of two different symmetry-related molecules at (x + 1, y, z) and (1 − x, 1 − y, 1 − z), respectively (Table 2). Carbonyl atom O1 of one molecule acts as an acceptor in another hydrogen-bond interaction with phenyl atom C18 in a symmetry-related molecule at (1 − x, y − 1/2, 1/2 − z) (Table 2). In addition, methyl atom C12 is involved in two separate C—H···π interactions, with C12···Cg1 4.070 (4) Å, H12A···Cg1 3.1 Å and C12—H12A···Cg1 163°, and C12···Cg2 4.001 (5) Å, H12B···Cg2 3.1 Å and C12—H12B···Cg2 133°, where Cg1 is the centre of gravity of the pyridine ring of the molecule at (1 + x, y, z) and Cg2 is the centre of gravity of the phenyl ring of the molecule at (2 − x, 1 − y, z) Please check this has been rephrased correctly. A comparatively weak π–π interaction between the thiophene ring and a symmetry-related pyridine ring at (1 − x, −y, 2 − z), with their centroids seperated by 3.721 (2) Å, is also observed in the structure of (I).

S2. Experimental

The title compound was synthesized according to the method of Shah (2000); the details of the synthesis will be published elsewhere by Dave et al. Plate-like single crystals of (I) were grown from a solution in ethyl acetate under slow evaporation.

S3. Refinement

H atoms were treated as riding, with C—H distances in the range 0.93–0.97 Å and N—H distances of 0.86 Å. Is this added text correct?

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: Please provide missing information; data reduction: NRCVAX (Gabe et al., 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. A view of the molecular structure of (I), showing the atom-numbering scheme and 50% probability displacement ellipsoids. H atoms have been omitted for clarity.
	Fig. 2. The molecular packing of (I) viewed on the bc plane, with the C—H···O and C—H···N interactions shown as dashed lines.

Ethyl 3-amino-6-phenyl-4-tolylthieno[2,3-b]pyridine-2-carboxylate

Crystal data

C23H20N2O2S	F(000) = 816
Mr = 388.47	Dx = 1.289 Mg m^−3 Dm = 1.289 Mg m^−3 Dm measured by flotation in aqueous potassium iodide
Monoclinic, P21/c	Mo Kα1 radiation, λ = 0.70930 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 9.200 (3) Å	θ = 25–35°
b = 22.465 (5) Å	µ = 0.18 mm^−1
c = 9.708 (3) Å	T = 293 K
β = 94.06 (3)°	Plate-like, light yellow
V = 2001.4 (10) Å^3	0.2 × 0.2 × 0.1 mm
Z = 4

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.000
Radiation source: fine-focus sealed tube	θmax = 24.9°, θmin = 2.2°
Graphite monochromator	h = −10→10
ω/2θ scans	k = 0→26
3513 measured reflections	l = 0→11
3513 independent reflections	2 standard reflections every 60 min
1922 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.058	w = 1/[σ^2(Fo^2) + (0.0763P)^2] where P is Please define
wR(F^2) = 0.156	(Δ/σ)max = 0.001
S = 0.98	Δρmax = 0.27 e Å^−3
3504 reflections	Δρmin = −0.23 e Å^−3
253 parameters

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.25735 (9)	0.57982 (4)	0.36908 (10)	0.0541 (3)
N1	0.2743 (3)	0.46300 (11)	0.4170 (3)	0.0452 (7)
N2	0.6155 (3)	0.58257 (14)	0.1697 (3)	0.0693 (9)
H2A	0.6281	0.6186	0.1432	0.083*
H2B	0.6761	0.5553	0.1497	0.083*
C5	0.3419 (3)	0.41030 (14)	0.4051 (3)	0.0450 (8)
O2	0.2873 (3)	0.70191 (11)	0.2975 (3)	0.0869 (9)
C4	0.4708 (3)	0.40581 (15)	0.3351 (4)	0.0529 (9)
H4	0.5131	0.3685	0.3262	0.063*
C2	0.4666 (3)	0.50964 (14)	0.2910 (3)	0.0439 (8)
C6	0.6786 (3)	0.44665 (14)	0.2154 (3)	0.0453 (8)
C19	0.4995 (3)	0.56869 (15)	0.2435 (3)	0.0512 (9)
O1	0.4894 (3)	0.69617 (12)	0.1767 (3)	0.0896 (9)
C1	0.3369 (3)	0.50983 (14)	0.3606 (3)	0.0439 (8)
C13	0.2755 (3)	0.35870 (14)	0.4729 (4)	0.0514 (9)
C3	0.5368 (3)	0.45445 (15)	0.2792 (3)	0.0469 (8)
C9	0.9478 (4)	0.42671 (16)	0.1046 (4)	0.0558 (9)
C18	0.3346 (4)	0.30191 (17)	0.4688 (5)	0.0761 (12)
H18	0.4161	0.2953	0.4194	0.091*
C7	0.6872 (4)	0.41533 (17)	0.0949 (4)	0.0625 (10)
H7	0.6026	0.4007	0.0488	0.075*
C8	0.8201 (4)	0.40528 (18)	0.0413 (4)	0.0690 (11)
H8	0.8233	0.3834	−0.0398	0.083*
C14	0.1542 (4)	0.36607 (16)	0.5475 (4)	0.0702 (11)
H14	0.1120	0.4036	0.5518	0.084*
C20	0.3974 (3)	0.61012 (15)	0.2797 (4)	0.0524 (9)
C11	0.8065 (3)	0.46833 (16)	0.2796 (4)	0.0582 (10)
H11	0.8032	0.4902	0.3606	0.070*
C10	0.9391 (4)	0.45808 (17)	0.2256 (4)	0.0612 (10)
H10	1.0239	0.4726	0.2716	0.073*
C15	0.0941 (4)	0.31918 (18)	0.6156 (5)	0.0856 (14)
H15	0.0118	0.3252	0.6642	0.103*
C21	0.3994 (4)	0.67236 (17)	0.2442 (4)	0.0666 (11)
C17	0.2745 (5)	0.25545 (18)	0.5366 (5)	0.0927 (15)
H17	0.3151	0.2177	0.5316	0.111*
C12	1.0942 (4)	0.41519 (19)	0.0452 (4)	0.0810 (13)
H12A	1.1704	0.4333	0.1035	0.122*
H12B	1.0935	0.4319	−0.0458	0.122*
H12C	1.1109	0.3731	0.0406	0.122*
C16	0.1559 (5)	0.26394 (18)	0.6114 (5)	0.0869 (13)
H16	0.1176	0.2324	0.6591	0.104*
C22	0.2800 (6)	0.76597 (19)	0.2798 (7)	0.1182 (19)
H22A	0.2418	0.7837	0.3609	0.142*
H22B	0.3777	0.7813	0.2723	0.142*
C23	0.1921 (7)	0.7829 (2)	0.1625 (6)	0.133 (2)
H23A	0.1909	0.8255	0.1553	0.200*
H23B	0.0947	0.7686	0.1703	0.200*
H23C	0.2306	0.7662	0.0817	0.200*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0481 (5)	0.0486 (5)	0.0678 (6)	0.0000 (4)	0.0187 (4)	0.0019 (5)
N1	0.0405 (15)	0.0437 (16)	0.0526 (17)	−0.0028 (12)	0.0118 (13)	−0.0063 (13)
N2	0.0526 (17)	0.072 (2)	0.086 (2)	−0.0038 (16)	0.0268 (16)	0.0185 (18)
C5	0.0387 (17)	0.054 (2)	0.043 (2)	−0.0044 (15)	0.0079 (15)	−0.0085 (15)
O2	0.0843 (19)	0.0505 (16)	0.130 (3)	0.0037 (14)	0.0339 (18)	0.0105 (16)
C4	0.0442 (18)	0.052 (2)	0.064 (2)	0.0027 (15)	0.0104 (17)	−0.0072 (17)
C2	0.0313 (16)	0.056 (2)	0.045 (2)	−0.0038 (15)	0.0049 (14)	0.0020 (16)
C6	0.0412 (18)	0.053 (2)	0.043 (2)	0.0018 (15)	0.0115 (15)	−0.0017 (16)
C19	0.0395 (17)	0.066 (2)	0.049 (2)	−0.0090 (16)	0.0063 (15)	0.0051 (17)
O1	0.0770 (19)	0.0750 (19)	0.120 (3)	−0.0176 (15)	0.0274 (17)	0.0302 (17)
C1	0.0380 (17)	0.051 (2)	0.043 (2)	−0.0022 (15)	0.0056 (14)	−0.0047 (16)
C13	0.0475 (19)	0.049 (2)	0.059 (2)	−0.0039 (16)	0.0125 (17)	−0.0068 (17)
C3	0.0378 (17)	0.060 (2)	0.043 (2)	−0.0004 (16)	0.0065 (15)	−0.0033 (16)
C9	0.047 (2)	0.064 (2)	0.058 (2)	0.0085 (18)	0.0207 (17)	0.0088 (19)
C18	0.073 (3)	0.060 (3)	0.101 (3)	0.001 (2)	0.042 (2)	0.001 (2)
C7	0.0463 (19)	0.087 (3)	0.055 (2)	−0.0020 (19)	0.0069 (17)	−0.014 (2)
C8	0.068 (3)	0.086 (3)	0.056 (2)	0.001 (2)	0.021 (2)	−0.014 (2)
C14	0.064 (2)	0.052 (2)	0.099 (3)	−0.0006 (18)	0.038 (2)	−0.001 (2)
C20	0.0465 (19)	0.051 (2)	0.060 (2)	−0.0046 (16)	0.0091 (17)	0.0080 (17)
C11	0.048 (2)	0.072 (2)	0.057 (2)	−0.0026 (18)	0.0130 (18)	−0.0120 (18)
C10	0.0401 (19)	0.083 (3)	0.061 (2)	−0.0060 (18)	0.0073 (17)	−0.005 (2)
C15	0.075 (3)	0.065 (3)	0.123 (4)	−0.009 (2)	0.051 (3)	0.002 (3)
C21	0.060 (2)	0.054 (2)	0.085 (3)	−0.010 (2)	0.007 (2)	0.007 (2)
C17	0.094 (3)	0.053 (2)	0.137 (4)	0.004 (2)	0.047 (3)	0.004 (3)
C12	0.059 (2)	0.092 (3)	0.097 (3)	0.015 (2)	0.037 (2)	0.004 (2)
C16	0.087 (3)	0.059 (3)	0.120 (4)	−0.006 (2)	0.043 (3)	0.012 (2)
C22	0.137 (5)	0.046 (3)	0.172 (6)	−0.004 (3)	0.017 (4)	0.012 (3)
C23	0.178 (6)	0.085 (4)	0.133 (5)	−0.010 (4)	−0.026 (5)	0.035 (4)

Geometric parameters (Å, º)

S1—C1	1.739 (3)	C18—C17	1.371 (5)
S1—C20	1.742 (3)	C18—H18	0.9300
N1—C1	1.335 (4)	C7—C8	1.381 (5)
N1—C5	1.346 (4)	C7—H7	0.9300
N2—C19	1.362 (4)	C8—H8	0.9300
N2—H2A	0.8600	C14—C15	1.380 (5)
N2—H2B	0.8600	C14—H14	0.9300
C5—C4	1.412 (4)	C20—C21	1.441 (5)
C5—C13	1.486 (4)	C11—C10	1.381 (4)
O2—C21	1.360 (4)	C11—H11	0.9300
O2—C22	1.450 (5)	C10—H10	0.9300
C4—C3	1.379 (4)	C15—C16	1.367 (5)
C4—H4	0.9300	C15—H15	0.9300
C2—C3	1.406 (4)	C17—C16	1.366 (5)
C2—C1	1.413 (4)	C17—H17	0.9300
C2—C19	1.444 (4)	C12—H12A	0.9600
C6—C7	1.372 (4)	C12—H12B	0.9600
C6—C11	1.380 (4)	C12—H12C	0.9600
C6—C3	1.494 (4)	C16—H16	0.9300
C19—C20	1.385 (5)	C22—C23	1.401 (7)
O1—C21	1.215 (4)	C22—H22A	0.9700
C13—C14	1.383 (4)	C22—H22B	0.9700
C13—C18	1.388 (5)	C23—H23A	0.9600
C9—C8	1.373 (5)	C23—H23B	0.9600
C9—C10	1.377 (5)	C23—H23C	0.9600
C9—C12	1.524 (4)
C1—S1—C20	90.07 (15)	C15—C14—C13	121.7 (4)
C1—N1—C5	116.3 (2)	C15—C14—H14	119.2
C19—N2—H2A	120.0	C13—C14—H14	119.2
C19—N2—H2B	120.0	C19—C20—C21	124.8 (3)
H2A—N2—H2B	120.0	C19—C20—S1	113.8 (2)
N1—C5—C4	120.9 (3)	C21—C20—S1	121.4 (3)
N1—C5—C13	116.2 (3)	C6—C11—C10	121.1 (3)
C4—C5—C13	122.9 (3)	C6—C11—H11	119.4
C21—O2—C22	118.0 (3)	C10—C11—H11	119.4
C3—C4—C5	122.7 (3)	C9—C10—C11	121.0 (3)
C3—C4—H4	118.6	C9—C10—H10	119.5
C5—C4—H4	118.6	C11—C10—H10	119.5
C3—C2—C1	116.7 (3)	C16—C15—C14	119.8 (4)
C3—C2—C19	132.6 (3)	C16—C15—H15	120.1
C1—C2—C19	110.7 (3)	C14—C15—H15	120.1
C7—C6—C11	117.8 (3)	O1—C21—O2	123.7 (4)
C7—C6—C3	121.2 (3)	O1—C21—C20	125.2 (4)
C11—C6—C3	120.8 (3)	O2—C21—C20	111.1 (3)
N2—C19—C20	123.4 (3)	C16—C17—C18	120.9 (4)
N2—C19—C2	124.6 (3)	C16—C17—H17	119.6
C20—C19—C2	112.0 (3)	C18—C17—H17	119.6
N1—C1—C2	126.7 (3)	C9—C12—H12A	109.5
N1—C1—S1	119.9 (2)	C9—C12—H12B	109.5
C2—C1—S1	113.4 (2)	H12A—C12—H12B	109.5
C14—C13—C18	117.2 (3)	C9—C12—H12C	109.5
C14—C13—C5	120.7 (3)	H12A—C12—H12C	109.5
C18—C13—C5	122.0 (3)	H12B—C12—H12C	109.5
C4—C3—C2	116.7 (3)	C17—C16—C15	119.5 (4)
C4—C3—C6	119.4 (3)	C17—C16—H16	120.3
C2—C3—C6	123.8 (3)	C15—C16—H16	120.3
C8—C9—C10	117.5 (3)	C23—C22—O2	112.6 (5)
C8—C9—C12	121.5 (3)	C23—C22—H22A	109.1
C10—C9—C12	121.0 (3)	O2—C22—H22A	109.1
C17—C18—C13	120.9 (3)	C23—C22—H22B	109.1
C17—C18—H18	119.5	O2—C22—H22B	109.1
C13—C18—H18	119.5	H22A—C22—H22B	107.8
C6—C7—C8	120.7 (3)	C22—C23—H23A	109.5
C6—C7—H7	119.6	C22—C23—H23B	109.5
C8—C7—H7	119.6	H23A—C23—H23B	109.5
C9—C8—C7	121.7 (3)	C22—C23—H23C	109.5
C9—C8—H8	119.1	H23A—C23—H23C	109.5
C7—C8—H8	119.1	H23B—C23—H23C	109.5
C1—N1—C5—C4	−0.7 (4)	C5—C13—C18—C17	177.5 (4)
C1—N1—C5—C13	177.6 (3)	C11—C6—C7—C8	0.9 (5)
N1—C5—C4—C3	2.0 (5)	C3—C6—C7—C8	−176.0 (3)
C13—C5—C4—C3	−176.1 (3)	C10—C9—C8—C7	1.0 (6)
C3—C2—C19—N2	1.0 (6)	C12—C9—C8—C7	179.7 (3)
C1—C2—C19—N2	−178.2 (3)	C6—C7—C8—C9	−0.9 (6)
C3—C2—C19—C20	179.9 (3)	C18—C13—C14—C15	0.2 (6)
C1—C2—C19—C20	0.8 (4)	C5—C13—C14—C15	−177.5 (4)
C5—N1—C1—C2	−0.5 (5)	N2—C19—C20—C21	0.3 (6)
C5—N1—C1—S1	179.5 (2)	C2—C19—C20—C21	−178.6 (3)
C3—C2—C1—N1	0.4 (5)	N2—C19—C20—S1	178.0 (3)
C19—C2—C1—N1	179.6 (3)	C2—C19—C20—S1	−0.9 (4)
C3—C2—C1—S1	−179.6 (2)	C1—S1—C20—C19	0.6 (3)
C19—C2—C1—S1	−0.3 (3)	C1—S1—C20—C21	178.4 (3)
C20—S1—C1—N1	179.9 (3)	C7—C6—C11—C10	−1.0 (5)
C20—S1—C1—C2	−0.2 (3)	C3—C6—C11—C10	175.9 (3)
N1—C5—C13—C14	−2.2 (5)	C8—C9—C10—C11	−1.1 (5)
C4—C5—C13—C14	176.0 (3)	C12—C9—C10—C11	−179.8 (3)
N1—C5—C13—C18	−179.8 (3)	C6—C11—C10—C9	1.1 (6)
C4—C5—C13—C18	−1.6 (5)	C13—C14—C15—C16	0.7 (7)
C5—C4—C3—C2	−2.0 (5)	C22—O2—C21—O1	−3.9 (6)
C5—C4—C3—C6	175.7 (3)	C22—O2—C21—C20	175.5 (4)
C1—C2—C3—C4	0.9 (4)	C19—C20—C21—O1	1.1 (6)
C19—C2—C3—C4	−178.2 (3)	S1—C20—C21—O1	−176.4 (3)
C1—C2—C3—C6	−176.8 (3)	C19—C20—C21—O2	−178.3 (3)
C19—C2—C3—C6	4.2 (5)	S1—C20—C21—O2	4.2 (4)
C7—C6—C3—C4	68.5 (4)	C13—C18—C17—C16	−0.8 (7)
C11—C6—C3—C4	−108.3 (4)	C18—C17—C16—C15	1.8 (8)
C7—C6—C3—C2	−113.9 (4)	C14—C15—C16—C17	−1.7 (8)
C11—C6—C3—C2	69.3 (4)	C21—O2—C22—C23	93.7 (6)
C14—C13—C18—C17	−0.2 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1	0.86	2.20	2.806 (4)	128
C14—H14···N1	0.93	2.45	2.787 (4)	101
C11—H11···N1^i	0.93	2.55	3.453 (4)	164
C18—H18···O1^ii	0.93	2.59	3.253 (5)	129
C10—H10···N1^iii	0.93	2.62	3.488 (4)	155

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