Ethyl 5-methyl­imidazo[1,2-a]pyridine-2-carboxyl­ate

Abstract

The title compound, C₁₁H₁₂N₂O₂, was synthesized from the reaction of 6-methyl­pyridin-2-amine and ethyl 3-bromo-2-oxopropionate. In the mol­ecular structure, the six- and five-membered rings are individually almost planar with r.m.s. deviations of 0.003 and 0.002 Å, respectively. The two rings are almost coplanar, the dihedral angle between their planes being 1.4 (3)°. Inter­molecular C—H⋯O and C—H⋯N hydrogen bonds are present in the crystal structure.

Related literature

For the biological properties of related compounds, see: Xia et al. (2005 ▶); Warshakoon et al. (2006 ▶); Imaeda et al. (2008 ▶). For the synthetic procedure, see: Xia et al. (2005 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

• C₁₁H₁₂N₂O₂

• M _r = 204.23

• Monoclinic,

• a = 17.164 (3) Å

• b = 10.521 (2) Å

• c = 13.759 (3) Å

• β = 124.77 (3)°

• V = 2041 (1) ų

• Z = 8

• Mo Kα radiation

• μ = 0.09 mm⁻¹

• T = 293 K

• 0.30 × 0.20 × 0.10 mm

Data collection

• Enraf–Nonius CAD-4 diffractometer

• Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.973, T _max = 0.991

• 1923 measured reflections

• 1859 independent reflections

• 1360 reflections with I > 2σ(I)

• R _int = 0.028

• 3 standard reflections every 200 reflections intensity decay: 1%

Refinement

• R[F ² > 2σ(F ²)] = 0.051

• wR(F ²) = 0.152

• S = 1.00

• 1859 reflections

• 137 parameters

• H-atom parameters constrained

• Δρ_max = 0.24 e Å⁻³

• Δρ_min = −0.20 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

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
C2—H2A⋯N1i	0.93	2.59	3.461 (4)	155
C3—H3A⋯O1i	0.93	2.58	3.456 (4)	157

Symmetry code: (i) .

supplementary crystallographic information

Comment

Imidazo[1,2a]pyridine derivatives are of great interest because of their chemical and pharmaceutical properties. Some derivatives play a key role in preparing hypoxia inducible factor 1α prolyl hydroxylase inhibitors. And HIF-1α is of great potential value for treating ischemic diseases (Warshakoon et al.,2006). Some can be used as a material for preparing a series of FXa inhibitors, which can be used to cure various kinds of thromboembolic diseases (Imaeda et al.,2008). Herein we report the crystal structure of the title compound, (I). The molecular structure of (I) is shown in Fig.1. In this structure ring A (C1/C2/C3/C4/N2/C7) is a planar six-mermbered ring and the mean deviation from plane is 0.0027 Å, ring B(C4/N1/C5/C6/N2) is a planar five-mermbered ring with a mean deviation from planarity of 0.0018 Å. The dihedral angle between A and B ring is 1.4 (3)°. In the crystal structure, intermolecular C—H···O and C—H···N hydrogen bonds (Table 1) link the molecules to form a trimeric unit (Fig. 2).

Experimental

6-Methyl-pyridin-2-ylamine (8 mmol) and 3-bromo-2-oxo-propionic acid ethyl ester (12 mmol) were added to 50 mL ethanol. The mixture was refluxed for 6 h and then the solvent was totally evaporated. Solid anhydrous KHCO₃ was added until pH=8 had been reached. Set aside for 3 h led to the observation of a white, flocculent precipitate, which was filtered and dried (yield ca. 52.6%, Xia et al. (2005)). Crystals suitable for X-ray analysis were obtained by dissolving (I) (0.5 g) in ethyl acetate (20 ml) and evaporating the solvent slowly at room temperature for about 10 d.

Refinement

All H atoms were positioned geometrically, with C—H= 0.97, 0.96 and 0.93 Å for methylene, methyl and aromatic H atoms, respectively, and constrained to ride on their parent atoms, with U_iso(H)=xU_eq(C), where x=1.5 for methyl H atoms and x=1.2 for all other H atoms.

Figures

Fig. 1.

A view of the molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level.

Fig. 2.

A packing diagram for (I). Dashed lines indicate an intermolecular C—H···N hydrogen bond and an intermolecular C—H···O hydrogen bond.

Crystal data

C11H12N2O2	F(000) = 864
Mr = 204.23	Dx = 1.329 Mg m−3
Monoclinic, C2/c	Melting point = 425–426 K
Hall symbol: -C 2yc	Mo Kα radiation, λ = 0.71073 Å
a = 17.164 (3) Å	Cell parameters from 25 reflections
b = 10.521 (2) Å	θ = 9–13°
c = 13.759 (3) Å	µ = 0.09 mm−1
β = 124.77 (3)°	T = 293 K
V = 2041 (1) Å3	Block, colorless
Z = 8	0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	1360 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.028
graphite	θmax = 25.3°, θmin = 2.4°
ω/2θ scans	h = −20→0
Absorption correction: ψ scan (North et al., 1968)	k = −12→0
Tmin = 0.973, Tmax = 0.991	l = −13→16
1923 measured reflections	3 standard reflections every 200 reflections
1859 independent reflections	intensity decay: 1%

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.051	H-atom parameters constrained
wR(F2) = 0.152	w = 1/[σ2(Fo2) + (0.1P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
1859 reflections	Δρmax = 0.24 e Å−3
137 parameters	Δρmin = −0.20 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0117 (17)

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.

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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.12866 (11)	0.40243 (18)	0.19751 (15)	0.0466 (5)
O1	0.07064 (11)	0.13738 (15)	0.15389 (15)	0.0602 (5)
C1	0.06679 (17)	0.7803 (2)	0.15626 (19)	0.0523 (6)
H1B	0.0502	0.8658	0.1452	0.063*
N2	0.02673 (11)	0.56505 (15)	0.13920 (13)	0.0376 (4)
O2	−0.07427 (10)	0.20448 (14)	0.09371 (13)	0.0512 (5)
C2	0.16246 (17)	0.7466 (3)	0.2109 (2)	0.0582 (6)
H2A	0.2075	0.8102	0.2346	0.070*
C3	0.19016 (14)	0.6232 (2)	0.22978 (18)	0.0527 (6)
H3A	0.2537	0.6020	0.2665	0.063*
C4	0.12108 (13)	0.5273 (2)	0.19286 (17)	0.0422 (5)
C5	0.03813 (14)	0.3590 (2)	0.14702 (17)	0.0408 (5)
C6	−0.02457 (13)	0.45553 (19)	0.11134 (16)	0.0387 (5)
H6A	−0.0896	0.4487	0.0751	0.046*
C7	−0.00174 (15)	0.6916 (2)	0.11927 (17)	0.0432 (5)
C8	−0.10473 (15)	0.7154 (2)	0.05724 (19)	0.0509 (6)
H8A	−0.1164	0.8053	0.0480	0.076*
H8B	−0.1260	0.6807	0.1028	0.076*
H8C	−0.1385	0.6757	−0.0192	0.076*
C9	0.01645 (14)	0.2218 (2)	0.13352 (17)	0.0432 (5)
C10	−0.10735 (16)	0.0748 (2)	0.0699 (2)	0.0560 (6)
H10A	−0.0701	0.0241	0.1412	0.067*
H10B	−0.1011	0.0386	0.0098	0.067*
C11	−0.20816 (17)	0.0755 (3)	0.0283 (2)	0.0727 (8)
H11A	−0.2321	−0.0099	0.0114	0.109*
H11B	−0.2443	0.1261	−0.0421	0.109*
H11C	−0.2134	0.1109	0.0887	0.109*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
N1	0.0347 (9)	0.0568 (12)	0.0450 (10)	0.0026 (8)	0.0208 (8)	0.0007 (8)
O1	0.0514 (10)	0.0524 (10)	0.0734 (11)	0.0127 (8)	0.0335 (9)	0.0054 (8)
C1	0.0589 (14)	0.0472 (13)	0.0525 (13)	−0.0098 (11)	0.0328 (11)	−0.0024 (10)
N2	0.0335 (9)	0.0460 (10)	0.0347 (9)	−0.0019 (7)	0.0202 (7)	−0.0025 (7)
O2	0.0443 (9)	0.0417 (9)	0.0654 (10)	−0.0026 (6)	0.0301 (8)	−0.0048 (7)
C2	0.0540 (14)	0.0666 (16)	0.0554 (13)	−0.0196 (12)	0.0320 (11)	−0.0058 (12)
C3	0.0362 (11)	0.0717 (17)	0.0488 (13)	−0.0106 (10)	0.0234 (10)	−0.0027 (11)
C4	0.0330 (10)	0.0564 (14)	0.0360 (10)	−0.0003 (9)	0.0188 (8)	−0.0004 (9)
C5	0.0365 (10)	0.0492 (12)	0.0365 (10)	0.0012 (9)	0.0207 (9)	0.0003 (9)
C6	0.0327 (10)	0.0457 (12)	0.0372 (10)	−0.0037 (9)	0.0196 (8)	−0.0020 (9)
C7	0.0474 (12)	0.0466 (13)	0.0387 (11)	−0.0031 (10)	0.0264 (9)	−0.0024 (9)
C8	0.0498 (13)	0.0447 (13)	0.0588 (13)	0.0022 (10)	0.0313 (11)	−0.0019 (10)
C9	0.0397 (11)	0.0491 (13)	0.0401 (11)	0.0056 (9)	0.0223 (9)	0.0022 (9)
C10	0.0557 (14)	0.0427 (13)	0.0662 (15)	−0.0034 (10)	0.0327 (12)	−0.0038 (11)
C11	0.0557 (15)	0.0608 (17)	0.092 (2)	−0.0087 (12)	0.0369 (15)	−0.0109 (14)

Geometric parameters (Å, °)

N1—C4	1.318 (3)	C3—H3A	0.9300
N1—C5	1.369 (2)	C5—C6	1.352 (3)
O1—C9	1.198 (2)	C5—C9	1.475 (3)
C1—C7	1.353 (3)	C6—H6A	0.9300
C1—C2	1.407 (3)	C7—C8	1.482 (3)
C1—H1B	0.9300	C8—H8A	0.9600
N2—C6	1.366 (2)	C8—H8B	0.9600
N2—C7	1.391 (3)	C8—H8C	0.9600
N2—C4	1.401 (2)	C10—C11	1.480 (3)
O2—C9	1.336 (2)	C10—H10A	0.9700
O2—C10	1.442 (3)	C10—H10B	0.9700
C2—C3	1.357 (4)	C11—H11A	0.9600
C2—H2A	0.9300	C11—H11B	0.9600
C3—C4	1.412 (3)	C11—H11C	0.9600
C4—N1—C5	104.84 (16)	C1—C7—C8	126.6 (2)
C7—C1—C2	121.8 (2)	N2—C7—C8	116.43 (18)
C7—C1—H1B	119.1	C7—C8—H8A	109.5
C2—C1—H1B	119.1	C7—C8—H8B	109.5
C6—N2—C7	130.90 (17)	H8A—C8—H8B	109.5
C6—N2—C4	105.97 (16)	C7—C8—H8C	109.5
C7—N2—C4	123.11 (16)	H8A—C8—H8C	109.5
C9—O2—C10	116.01 (17)	H8B—C8—H8C	109.5
C3—C2—C1	121.2 (2)	O1—C9—O2	124.2 (2)
C3—C2—H2A	119.4	O1—C9—C5	126.1 (2)
C1—C2—H2A	119.4	O2—C9—C5	109.67 (17)
C2—C3—C4	119.0 (2)	O2—C10—C11	107.8 (2)
C2—C3—H3A	120.5	O2—C10—H10A	110.2
C4—C3—H3A	120.5	C11—C10—H10A	110.2
N1—C4—N2	111.15 (17)	O2—C10—H10B	110.2
N1—C4—C3	130.93 (19)	C11—C10—H10B	110.2
N2—C4—C3	117.91 (19)	H10A—C10—H10B	108.5
C6—C5—N1	111.79 (19)	C10—C11—H11A	109.5
C6—C5—C9	126.71 (19)	C10—C11—H11B	109.5
N1—C5—C9	121.48 (18)	H11A—C11—H11B	109.5
C5—C6—N2	106.24 (17)	C10—C11—H11C	109.5
C5—C6—H6A	126.9	H11A—C11—H11C	109.5
N2—C6—H6A	126.9	H11B—C11—H11C	109.5
C1—C7—N2	117.0 (2)
C7—C1—C2—C3	−0.6 (3)	C4—N2—C6—C5	−0.42 (19)
C1—C2—C3—C4	0.4 (3)	C2—C1—C7—N2	0.9 (3)
C5—N1—C4—N2	−0.5 (2)	C2—C1—C7—C8	−177.8 (2)
C5—N1—C4—C3	−179.0 (2)	C6—N2—C7—C1	−178.96 (19)
C6—N2—C4—N1	0.6 (2)	C4—N2—C7—C1	−1.2 (3)
C7—N2—C4—N1	−177.71 (17)	C6—N2—C7—C8	−0.2 (3)
C6—N2—C4—C3	179.30 (17)	C4—N2—C7—C8	177.64 (16)
C7—N2—C4—C3	1.0 (3)	C10—O2—C9—O1	−2.8 (3)
C2—C3—C4—N1	177.8 (2)	C10—O2—C9—C5	176.75 (17)
C2—C3—C4—N2	−0.6 (3)	C6—C5—C9—O1	171.5 (2)
C4—N1—C5—C6	0.2 (2)	N1—C5—C9—O1	−6.9 (3)
C4—N1—C5—C9	178.87 (19)	C6—C5—C9—O2	−8.0 (3)
N1—C5—C6—N2	0.2 (2)	N1—C5—C9—O2	173.49 (16)
C9—C5—C6—N2	−178.43 (18)	C9—O2—C10—C11	179.40 (18)
C7—N2—C6—C5	177.67 (18)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2A···N1i	0.93	2.59	3.461 (4)	155
C3—H3A···O1i	0.93	2.58	3.456 (4)	157

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