6-Bromo-2-(4-meth­oxy­phen­yl)-3-methyl-3H-imidazo[4,5-b]pyridine

Bourichi, S.; Kandri Rodi, Y.; Jasinski, J.P.; Kaur, M.; El Hadrami, E.M.; Essassi, E.M.

doi:10.1107/S2414314617010719

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 7| July 2017| x171071

https://doi.org/10.1107/S2414314617010719

Open

access

6-Bromo-2-(4-methoxyphenyl)-3-methyl-3H-imidazo[4,5-b]pyridine

Selma Bourichi,^a ^* Youssef Kandri Rodi,^a Jerry P. Jasinski,^b Manpreet Kaur,^b El Mestafa El Hadrami ^a and El Mokhtar Essassi ^c

^aLaboratoire de Chimie Organique Appliquée, Faculté des Sciences et Techniques, Université Sidi Mohammed Ben Abdellah, Fès, Morocco, ^bDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA, and ^cLaboratoire de Chimie Organique Hétérocyclique URAC 21, Pôle de Compétence Pharmacochimie, Av. Ibn Battouta, BP 1014, Faculté des Sciences, Université Mohammed V, Rabat, Morocco
^*Correspondence e-mail: bourichiselma@hotmail.com

Edited by J. Simpson, University of Otago, New Zealand (Received 13 July 2017; accepted 20 July 2017; online 25 July 2017)

In the title compound, C₁₄H₁₂BrN₃O, the dihedral angle between the mean planes of the imidazo[4,5-b]pyridine ring system and the methoxyphenyl ring is 41.53 (12)°. In the crystal, weak C—H⋯N hydrogen bonds link the molecules into chains along the c-axis direction. Weak π–π stacking interactions involving the imidazole and the methoxyphenyl rings further stabilize the crystal packing.

Keywords: crystal structure; imidazo[4,5-b]pyridine; alkylation.

CCDC reference: 1563558

Structure description

Derivatives of imidazopyridine exhibit several remarkable pharmacological activities. For example they are used as antiviral (Scribner et al. 2007 ), antibacterial (Liang et al. 2007 ) and anti-neuroinflammatory agents (Ock et al., 2010 ). As a continuation of our research on the development of substituted imidazo[4,5-b]pyridine derivatives (Bourichi et al., 2017 ), we report here the synthesis and structure of a new imidazo[4,5-b]pyridine derivative synthesized by the reaction of methyl iodide and 6-bromo-2-(4-methoxyphenyl)-3H-imidazopyridine in the presence of a catalytic quantity of tetra-n-butylammonium bromide under phase transfer catalysis conditions.

The title compound crystallizes with one independent molecule in the asymmetric unit (Fig. 1). The molecule is slightly twisted, as is evident from the dihedral angle of 41.53 (12)° between the mean planes of the imidazo[4,5-b]pyridine ring system and the methoxyphenyl ring. In the crystal, a single weak C13—H13C⋯N1 intermolecular interaction links the molecules into chains along the c-axis direction (Table 1, Fig. 2). In addition, weak π–π stacking interactions involving the imidazole and the methoxyphenyl rings further stabilize the crystal packing [intercentroid distance, Cg1⋯Cg3ⁱⁱ = 3.8289 (2) Å, symmetry code: (ii) = 1 − x, − $[{1\over 2}]$ + y, $[{1\over 2}]$ − z; Cg1 and Cg3 are the centroids of the N1/C1/N2/C2/C6 and C7–C12 rings, respectively].

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13C⋯N1ⁱ	0.96	2.53	3.480 (3)	169
Symmetry code: (i) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Figure 1
Structure of the title compound, showing the atom-numbering scheme and ellipsoids drawn at the 30% probability level.

Figure 2
Molecular packing for the title compound, viewed along the b axis. Hydrogen bonds are drawn as dashed lines and H atoms not involved in these interactions have been omitted for clarity.

Synthesis and crystallization

To a solution of 6-bromo-2-(4-methoxyphenyl)-3H-imidazopyridine (0.2 g, 0.65 mmol) in DMF (25 ml) was added potassium carbonate (0.12 g, 0.9 mmol). The mixture was stirred magnetically for 5 min and then tetra-n-butylammonium bromide (0.032 g, 0.1 mmol) and methyl iodide (0.10 ml, 0.78 mmol) were added. Stirring was continued at room temperature for 6 h. After removing the salts by filtration, the DMF was evaporated under reduced pressure and the residue obtained was dissolved in dichloromethane. The remaining salts were extracted with distilled water and the resulting mixture was chromatographed on a silica-gel column (eluent: ethyl acetate/hexane, 1:3). Colourless crystals were isolated when the solvent was allowed to evaporate (yield 67%, m.p. 164–165° C).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₄H₁₂BrN₃O
M_r	318.18
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	14.8643 (6), 7.6795 (4), 12.0690 (5)
β (°)	108.465 (4)
V (Å³)	1306.75 (11)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	4.25
Crystal size (mm)	0.26 × 0.24 × 0.12

Data collection
Diffractometer	Rigaku Oxford Diffraction
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku Oxford Diffraction, 2015 $[Rigaku Oxford Diffraction (2015). CrysAlis PRO. Rigaku Americas, The Woodlands, Texas, USA.]$ )
T_min, T_max	0.354, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	4519, 2477, 2015
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.614

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.107, 1.05
No. of reflections	2477
No. of parameters	175
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.37
Computer programs: CrysAlis PRO (Rigaku Oxford Diffraction, 2015 $[Rigaku Oxford Diffraction (2015). CrysAlis PRO. Rigaku Americas, The Woodlands, Texas, USA.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1563558

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314617010719/sj4128sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617010719/sj4128Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617010719/sj4128Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2414314617010719/sj4128Isup4.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku Oxford Diffraction, 2015); cell refinement: CrysAlis PRO (Rigaku Oxford Diffraction, 2015); data reduction: CrysAlis PRO (Rigaku Oxford Diffraction, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

6-Bromo-2-(4-methoxyphenyl)-3-methyl-3H-imidazo[4,5-b]pyridine top

Crystal data top

C₁₄H₁₂BrN₃O	F(000) = 640
M_r = 318.18	D_x = 1.617 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 14.8643 (6) Å	Cell parameters from 1624 reflections
b = 7.6795 (4) Å	θ = 3.8–71.4°
c = 12.0690 (5) Å	µ = 4.25 mm⁻¹
β = 108.465 (4)°	T = 293 K
V = 1306.75 (11) Å³	Prism, colourless
Z = 4	0.26 × 0.24 × 0.12 mm

Data collection top

Rigaku Oxford diffraction diffractometer	2477 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Cu) X-ray Source	2015 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.026
Detector resolution: 16.0416 pixels mm^-1	θ_max = 71.3°, θ_min = 6.3°
ω scans	h = −17→18
Absorption correction: multi-scan (CrysAlis PRO; Rigaku Oxford Diffraction, 2015)	k = −9→7
T_min = 0.354, T_max = 1.000	l = −14→12
4519 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.039	w = 1/[σ²(F_o²) + (0.0523P)² + 0.0898P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.107	(Δ/σ)_max = 0.001
S = 1.05	Δρ_max = 0.39 e Å⁻³
2477 reflections	Δρ_min = −0.37 e Å⁻³
175 parameters	Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0104 (5)
Primary atom site location: dual

Special details top

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

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

	x	y	z	U_iso*/U_eq
Br1	0.95243 (2)	0.30457 (6)	0.64922 (3)	0.0757 (2)
O1	0.14946 (16)	0.3891 (4)	0.0701 (2)	0.0741 (7)
N1	0.57950 (16)	0.3218 (3)	0.41193 (19)	0.0418 (5)
N2	0.60882 (15)	0.4032 (3)	0.24692 (17)	0.0367 (5)
N3	0.77969 (16)	0.4084 (3)	0.31660 (19)	0.0468 (5)
C1	0.54200 (18)	0.3648 (3)	0.3004 (2)	0.0371 (5)
C2	0.69556 (18)	0.3826 (3)	0.3305 (2)	0.0372 (5)
C3	0.8520 (2)	0.3820 (4)	0.4124 (3)	0.0506 (7)
H3	0.9130	0.3978	0.4088	0.061*
C4	0.8416 (2)	0.3316 (4)	0.5193 (2)	0.0476 (6)
C5	0.7541 (2)	0.3027 (4)	0.5315 (2)	0.0441 (6)
H5	0.7472	0.2658	0.6017	0.053*
C6	0.67646 (19)	0.3320 (3)	0.4325 (2)	0.0386 (6)
C7	0.43977 (18)	0.3688 (4)	0.2376 (2)	0.0403 (6)
C8	0.3766 (2)	0.4354 (4)	0.2917 (2)	0.0470 (6)
H8	0.3997	0.4782	0.3675	0.056*
C9	0.2809 (2)	0.4381 (4)	0.2341 (3)	0.0542 (7)
H9	0.2397	0.4818	0.2714	0.065*
C10	0.2451 (2)	0.3758 (4)	0.1202 (3)	0.0521 (7)
C11	0.3059 (2)	0.3046 (4)	0.0662 (3)	0.0499 (7)
H11	0.2822	0.2589	−0.0088	0.060*
C12	0.4027 (2)	0.3022 (3)	0.1251 (2)	0.0446 (6)
H12	0.4436	0.2551	0.0885	0.053*
C13	0.5959 (2)	0.4800 (4)	0.1325 (2)	0.0442 (6)
H13A	0.6519	0.5435	0.1341	0.066*
H13B	0.5425	0.5576	0.1131	0.066*
H13C	0.5846	0.3893	0.0749	0.066*
C15	0.1094 (3)	0.3397 (6)	−0.0496 (4)	0.0848 (13)
H15A	0.1385	0.4059	−0.0964	0.127*
H15B	0.0424	0.3621	−0.0749	0.127*
H15C	0.1202	0.2179	−0.0578	0.127*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.0492 (2)	0.1056 (4)	0.0576 (3)	−0.01003 (18)	−0.00400 (16)	0.0134 (2)
O1	0.0440 (11)	0.0872 (17)	0.0781 (16)	−0.0058 (12)	0.0008 (11)	0.0013 (15)
N1	0.0420 (11)	0.0494 (13)	0.0327 (10)	−0.0049 (9)	0.0100 (9)	0.0067 (9)
N2	0.0451 (11)	0.0371 (11)	0.0284 (9)	0.0023 (9)	0.0123 (8)	0.0014 (8)
N3	0.0477 (12)	0.0560 (14)	0.0403 (11)	0.0020 (11)	0.0190 (10)	0.0032 (11)
C1	0.0437 (13)	0.0341 (13)	0.0319 (11)	−0.0015 (10)	0.0097 (10)	0.0027 (10)
C2	0.0457 (13)	0.0356 (13)	0.0310 (11)	0.0022 (10)	0.0133 (10)	−0.0011 (10)
C3	0.0449 (14)	0.0584 (18)	0.0505 (15)	−0.0022 (13)	0.0179 (12)	0.0009 (14)
C4	0.0438 (14)	0.0534 (17)	0.0393 (13)	−0.0015 (12)	0.0040 (11)	0.0009 (12)
C5	0.0487 (14)	0.0497 (16)	0.0318 (12)	−0.0059 (12)	0.0095 (11)	0.0031 (11)
C6	0.0447 (13)	0.0389 (14)	0.0323 (12)	−0.0045 (10)	0.0124 (10)	0.0019 (10)
C7	0.0429 (13)	0.0383 (13)	0.0371 (12)	−0.0017 (11)	0.0091 (10)	0.0075 (11)
C8	0.0507 (15)	0.0496 (16)	0.0400 (13)	−0.0034 (12)	0.0134 (11)	−0.0010 (12)
C9	0.0485 (15)	0.0588 (18)	0.0569 (17)	−0.0002 (14)	0.0190 (13)	−0.0031 (15)
C10	0.0460 (15)	0.0474 (16)	0.0561 (17)	−0.0068 (12)	0.0067 (13)	0.0070 (14)
C11	0.0547 (16)	0.0498 (17)	0.0388 (13)	−0.0116 (13)	0.0058 (12)	0.0007 (12)
C12	0.0521 (15)	0.0422 (15)	0.0390 (13)	−0.0050 (12)	0.0136 (12)	0.0002 (12)
C13	0.0535 (14)	0.0510 (16)	0.0296 (11)	0.0045 (12)	0.0153 (10)	0.0041 (11)
C15	0.061 (2)	0.086 (3)	0.080 (3)	−0.012 (2)	−0.016 (2)	0.001 (2)

Geometric parameters (Å, º) top

Br1—C4	1.892 (3)	C7—C8	1.399 (4)
O1—C10	1.361 (4)	C7—C12	1.392 (4)
O1—C15	1.428 (5)	C8—H8	0.9300
N1—C1	1.325 (3)	C8—C9	1.371 (4)
N1—C6	1.385 (3)	C9—H9	0.9300
N2—C1	1.377 (3)	C9—C10	1.393 (4)
N2—C2	1.371 (3)	C10—C11	1.383 (5)
N2—C13	1.457 (3)	C11—H11	0.9300
N3—C2	1.328 (3)	C11—C12	1.388 (4)
N3—C3	1.321 (4)	C12—H12	0.9300
C1—C7	1.468 (3)	C13—H13A	0.9600
C2—C6	1.404 (3)	C13—H13B	0.9600
C3—H3	0.9300	C13—H13C	0.9600
C3—C4	1.402 (4)	C15—H15A	0.9600
C4—C5	1.372 (4)	C15—H15B	0.9600
C5—H5	0.9300	C15—H15C	0.9600
C5—C6	1.392 (4)

C10—O1—C15	118.2 (3)	C7—C8—H8	119.6
C1—N1—C6	104.3 (2)	C9—C8—C7	120.8 (3)
C1—N2—C13	129.2 (2)	C9—C8—H8	119.6
C2—N2—C1	106.3 (2)	C8—C9—H9	119.8
C2—N2—C13	123.7 (2)	C8—C9—C10	120.4 (3)
C3—N3—C2	113.8 (2)	C10—C9—H9	119.8
N1—C1—N2	113.3 (2)	O1—C10—C9	115.6 (3)
N1—C1—C7	124.3 (2)	O1—C10—C11	124.5 (3)
N2—C1—C7	122.4 (2)	C11—C10—C9	119.9 (3)
N2—C2—C6	105.8 (2)	C10—C11—H11	120.3
N3—C2—N2	126.4 (2)	C10—C11—C12	119.3 (3)
N3—C2—C6	127.7 (2)	C12—C11—H11	120.3
N3—C3—H3	118.2	C7—C12—H12	119.3
N3—C3—C4	123.5 (3)	C11—C12—C7	121.4 (3)
C4—C3—H3	118.2	C11—C12—H12	119.3
C3—C4—Br1	118.2 (2)	N2—C13—H13A	109.5
C5—C4—Br1	120.0 (2)	N2—C13—H13B	109.5
C5—C4—C3	121.9 (3)	N2—C13—H13C	109.5
C4—C5—H5	122.0	H13A—C13—H13B	109.5
C4—C5—C6	116.0 (2)	H13A—C13—H13C	109.5
C6—C5—H5	122.0	H13B—C13—H13C	109.5
N1—C6—C2	110.3 (2)	O1—C15—H15A	109.5
N1—C6—C5	132.7 (2)	O1—C15—H15B	109.5
C5—C6—C2	117.1 (2)	O1—C15—H15C	109.5
C8—C7—C1	120.3 (2)	H15A—C15—H15B	109.5
C12—C7—C1	121.4 (3)	H15A—C15—H15C	109.5
C12—C7—C8	118.2 (3)	H15B—C15—H15C	109.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C13—H13C···N1ⁱ	0.96	2.53	3.480 (3)	169

Symmetry code: (i) x, −y+1/2, z−1/2.

Acknowledgements

JPJ acknowledges the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

References

Bourichi, S., Kandri Rodi, Y., Jasinski, J. P., Kaur, M., Ouzidan, Y. & Essassi, E. M. (2017). IUCrData, 2, x170899. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Liang, G. B., Qian, X., Feng, D., Fisher, M., Brown, C. M., Gurnett, A., Leavitt, P. S., Liberator, P. A., Misura, A. S., Tamas, T., Schmatz, D. M., Wyvratt, M. & Biftu, T. (2007). Bioorg. Med. Chem. Lett. 17, 3558–3561. Web of Science CrossRef PubMed CAS Google Scholar
Ock, J., Kim, S., Yi, K. Y., Kim, N. J., Han, H. S., Cho, J. Y. & Suk, K. (2010). Biochem. Pharmacol. 79, 596–609. CrossRef PubMed CAS Google Scholar
Rigaku Oxford Diffraction (2015). CrysAlis PRO. Rigaku Americas, The Woodlands, Texas, USA. Google Scholar
Scribner, A., Dennis, R., Hong, J., Lee, S., McIntyre, D., Perrey, D., Feng, D., Fisher, M., Wyvratt, M., Leavitt, M., Liberator, P., Gurnett, A., Brown, C., Mathew, J., Thompson, D., Schmatz, D. & Biftu, T. (2007). Eur. J. Med. Chem. 42, 1334–1357. CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.