2-(6-Bromo-3-pyrid­yl)-8-methyl­imidazo[1,2-a]pyrazine

Huang, B.; Rui, E.; Wythes, M.; Kung, P.-P.; Moore, C.; Rheingold, A.L.; Yanovsky, A.

doi:10.1107/S1600536810022993

organic compounds

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Volume 66| Part 7| July 2010| Page o1723

doi:10.1107/S1600536810022993

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2-(6-Bromo-3-pyridyl)-8-methylimidazo[1,2-a]pyrazine

Buwen Huang,^a Eugene Rui,^a Martin Wythes,^a Pei-Pei Kung,^a Curtis Moore,^b Arnold L. Rheingold ^b and Alex Yanovsky ^a ^*

^aPfizer Global Research and Development, La Jolla Labs, 10770 Science Center Drive, San Diego, CA 92121, USA, and ^bDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
^*Correspondence e-mail: alex.yanovsky@pfizer.com

(Received 1 June 2010; accepted 14 June 2010; online 23 June 2010)

The structure of the title compound, C₁₂H₉BrN₄, prepared by the reaction of 2-bromo-1-(6-bromo-3-pyridyl)ethanone with 2-amino-3-methylpyrazine indicates that the compound with the bromopyridyl substituent at position 2 of the imidazopyrazine fused-ring system represents the major product of this reaction. The plane of the pyridine ring forms a dihedral angle of 16.2 (2)° with the essentially planar (r.m.s. deviation = 0.006 Å) imidazopyrazine system. In the crystal, molecules are linked by weak C—H⋯N interactions.

Related literature

For the structure of the related imidazo(1,2-a)pyrazine deivative, see: Lumma & Springer (1981 ).

Experimental

Crystal data

C₁₂H₉BrN₄
M_r = 289.14
Monoclinic, P 2₁ /n
a = 3.9007 (14) Å
b = 13.545 (5) Å
c = 20.673 (8) Å
β = 93.059 (5)°
V = 1090.7 (7) Å³
Z = 4
Mo Kα radiation
μ = 3.75 mm⁻¹
T = 100 K
0.27 × 0.11 × 0.05 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.431, T_max = 0.835
19939 measured reflections
2668 independent reflections
1887 reflections with I > 2σ(I)
R_int = 0.085

Refinement

R[F² > 2σ(F²)] = 0.057
wR(F²) = 0.154
S = 1.05
2668 reflections
155 parameters
H-atom parameters constrained
Δρ_max = 1.23 e Å⁻³
Δρ_min = −1.30 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7⋯N1ⁱ	0.95	2.52	3.438 (6)	163
C10—H10⋯N2ⁱⁱ	0.95	2.60	3.484 (7)	156
Symmetry codes: (i) -x+1, -y+2, -z+2; (ii) $[-x+{\script{5\over 2}}, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: APEX2 (Bruker, 2007 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; 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: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810022993/hb5478sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810022993/hb5478Isup2.hkl

checkCIF report

Comment top

The reaction of 2-bromo-1-(6-bromo3-pyridyl)ethanone with 2-amino-3-methylpyrazine may potentially produce either 2- or 3-(6-bromo3-pyridyl)-8-methylimidazo[1,2-a]pyrazine. The present study shows that the compound with bromopyridyl substituent in position 2 of imidazopyrazine represents the major product of this reaction (Fig. 1).

The plane of the pyridine ring N1, C1—C5 forms the dihedral angle of 16.2 (2)° with the essentially planar imidazopyrazine system N2, N3, N4, C6—C11. Strange though it may seem, only one purely organic structure with non-protontated non-fused imidazo(1,2 - a)pyrazine system with only carbon substituents has been published heretofore (Lumma & Springer, 1981). The geometry of the bicyclic fragment in this structure is in good agreement with that of the title compound.

Related literature top

For the structure of the related imidazo(1,2-a)pyrazine deivative, see: Lumma & Springer (1981).

Experimental top

A mixture of 2-bromo-1-(6-bromo-3-pyridyl)-ethanone (2.70 g, 9.68 mmol), 2-amino-3-methylpyrazine (1.06 g, 9.68 mmol), and sodium bicarbonate (1.22 g, 14.5 mmol) in 40 ml of 2-propanol was heated at 80°C overnight. After cooling down to rt, the reaction mixture was concentrated to dryness. The resulting residue was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with brine (1 × 100 ml), dried over sodium sulfate, concentrated to dryness, and purified by column chromatography with 0 --> 5% MeOH/EA to afford the desired product as a solid (1.25 g, 44.7% yield).

Colourless needles of (I) were grown by slow evaporation of an ethanol/dichloroethane solution.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); 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: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. Molecular structure of the title compound, showing 50% probability displacement ellipsoids. H atoms are drawn as circles of arbitrary small radius.

2-(6-Bromo-3-pyridyl)-8-methylimidazo[1,2-a]pyrazine top

Crystal data top

C₁₂H₉BrN₄	F(000) = 576
M_r = 289.14	D_x = 1.761 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 6098 reflections
a = 3.9007 (14) Å	θ = 3.3–27.2°
b = 13.545 (5) Å	µ = 3.75 mm⁻¹
c = 20.673 (8) Å	T = 100 K
β = 93.059 (5)°	Needle, colorless
V = 1090.7 (7) Å³	0.27 × 0.11 × 0.05 mm
Z = 4

Data collection top

Bruker APEXII CCD diffractometer	2668 independent reflections
Radiation source: fine-focus sealed tube	1887 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.085
ϕ and ω scans	θ_max = 28.7°, θ_min = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −5→5
T_min = 0.431, T_max = 0.835	k = −17→17
19939 measured reflections	l = −27→26

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.154	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0701P)² + 3.9758P] where P = (F_o² + 2F_c²)/3
2668 reflections	(Δ/σ)_max = 0.001
155 parameters	Δρ_max = 1.23 e Å⁻³
0 restraints	Δρ_min = −1.30 e Å⁻³

Crystal data top

C₁₂H₉BrN₄	V = 1090.7 (7) Å³
M_r = 289.14	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 3.9007 (14) Å	µ = 3.75 mm⁻¹
b = 13.545 (5) Å	T = 100 K
c = 20.673 (8) Å	0.27 × 0.11 × 0.05 mm
β = 93.059 (5)°

Data collection top

Bruker APEXII CCD diffractometer	2668 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	1887 reflections with I > 2σ(I)
T_min = 0.431, T_max = 0.835	R_int = 0.085
19939 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.057	0 restraints
wR(F²) = 0.154	H-atom parameters constrained
S = 1.05	Δρ_max = 1.23 e Å⁻³
2668 reflections	Δρ_min = −1.30 e Å⁻³
155 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
Br1	0.27478 (13)	0.63452 (4)	1.03763 (3)	0.0279 (2)
N1	0.5377 (11)	0.8165 (3)	1.0087 (2)	0.0247 (9)
N2	1.0290 (10)	0.9281 (3)	0.8097 (2)	0.0195 (8)
N3	1.0640 (10)	1.0898 (3)	0.83304 (19)	0.0193 (8)
N4	1.4045 (11)	1.1347 (3)	0.7232 (2)	0.0221 (9)
C1	0.4653 (12)	0.7301 (4)	0.9823 (2)	0.0215 (10)
C2	0.5223 (13)	0.7047 (4)	0.9189 (2)	0.0241 (11)
H2	0.4687	0.6407	0.9026	0.029*
C3	0.6590 (12)	0.7755 (4)	0.8807 (2)	0.0214 (10)
H3	0.7011	0.7611	0.8369	0.026*
C4	0.7370 (12)	0.8692 (3)	0.9062 (2)	0.0190 (10)
C5	0.6736 (12)	0.8850 (4)	0.9704 (2)	0.0220 (10)
H5	0.7290	0.9478	0.9887	0.026*
C6	0.8818 (12)	0.9470 (3)	0.8672 (2)	0.0185 (10)
C7	0.8997 (12)	1.0472 (3)	0.8822 (2)	0.0207 (10)
H7	0.8150	1.0790	0.9191	0.025*
C8	1.1395 (12)	1.0161 (3)	0.7898 (2)	0.0174 (9)
C9	1.3167 (12)	1.0417 (4)	0.7337 (2)	0.0207 (10)
C10	1.3238 (13)	1.2048 (4)	0.7677 (3)	0.0256 (11)
H10	1.3897	1.2710	0.7598	0.031*
C11	1.1591 (13)	1.1865 (3)	0.8214 (3)	0.0224 (10)
H11	1.1088	1.2380	0.8507	0.027*
C12	1.4005 (13)	0.9642 (4)	0.6864 (2)	0.0241 (11)
H12A	1.5153	0.9944	0.6503	0.036*
H12B	1.1887	0.9319	0.6700	0.036*
H12C	1.5530	0.9152	0.7077	0.036*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.0245 (3)	0.0267 (3)	0.0331 (3)	−0.0011 (2)	0.0081 (2)	0.0102 (2)
N1	0.027 (2)	0.024 (2)	0.023 (2)	0.0019 (18)	0.0048 (17)	0.0007 (18)
N2	0.018 (2)	0.0173 (19)	0.024 (2)	0.0029 (16)	0.0018 (16)	−0.0005 (16)
N3	0.018 (2)	0.016 (2)	0.025 (2)	0.0009 (16)	0.0031 (16)	0.0015 (16)
N4	0.021 (2)	0.018 (2)	0.027 (2)	−0.0009 (17)	0.0047 (16)	0.0024 (17)
C1	0.017 (2)	0.023 (2)	0.025 (2)	0.0025 (19)	0.0039 (18)	0.008 (2)
C2	0.024 (3)	0.019 (2)	0.029 (3)	−0.001 (2)	0.005 (2)	−0.002 (2)
C3	0.019 (2)	0.022 (2)	0.023 (2)	−0.0002 (19)	0.0032 (19)	−0.001 (2)
C4	0.017 (2)	0.020 (2)	0.020 (2)	0.0028 (19)	0.0033 (17)	0.0016 (19)
C5	0.023 (2)	0.022 (2)	0.022 (2)	0.0055 (19)	−0.0005 (19)	−0.0042 (19)
C6	0.015 (2)	0.020 (2)	0.021 (2)	0.0061 (18)	0.0003 (18)	0.0002 (19)
C7	0.025 (3)	0.016 (2)	0.022 (2)	0.0009 (19)	0.0065 (19)	−0.0035 (19)
C8	0.016 (2)	0.015 (2)	0.021 (2)	0.0013 (17)	0.0026 (18)	0.0006 (18)
C9	0.017 (2)	0.019 (2)	0.026 (2)	0.0029 (19)	0.0026 (19)	0.003 (2)
C10	0.027 (3)	0.019 (2)	0.031 (3)	−0.001 (2)	0.001 (2)	0.001 (2)
C11	0.020 (2)	0.013 (2)	0.034 (3)	0.0008 (18)	0.002 (2)	−0.003 (2)
C12	0.024 (3)	0.027 (3)	0.021 (2)	0.002 (2)	0.0069 (19)	0.000 (2)

Geometric parameters (Å, º) top

Br1—C1	1.905 (5)	C3—H3	0.9500
N1—C1	1.316 (7)	C4—C5	1.381 (7)
N1—C5	1.347 (7)	C4—C6	1.458 (7)
N2—C8	1.340 (6)	C5—H5	0.9500
N2—C6	1.371 (6)	C6—C7	1.393 (7)
N3—C7	1.359 (6)	C7—H7	0.9500
N3—C8	1.382 (6)	C8—C9	1.424 (7)
N3—C11	1.386 (6)	C9—C12	1.482 (7)
N4—C9	1.327 (6)	C10—C11	1.335 (7)
N4—C10	1.371 (7)	C10—H10	0.9500
C1—C2	1.384 (7)	C11—H11	0.9500
C2—C3	1.369 (7)	C12—H12A	0.9800
C2—H2	0.9500	C12—H12B	0.9800
C3—C4	1.401 (7)	C12—H12C	0.9800

C1—N1—C5	116.8 (4)	C7—C6—C4	126.6 (4)
C8—N2—C6	104.9 (4)	N3—C7—C6	105.4 (4)
C7—N3—C8	107.6 (4)	N3—C7—H7	127.3
C7—N3—C11	132.2 (4)	C6—C7—H7	127.3
C8—N3—C11	120.2 (4)	N2—C8—N3	111.1 (4)
C9—N4—C10	118.5 (4)	N2—C8—C9	130.2 (4)
N1—C1—C2	125.0 (5)	N3—C8—C9	118.7 (4)
N1—C1—Br1	115.9 (4)	N4—C9—C8	120.4 (4)
C2—C1—Br1	119.1 (4)	N4—C9—C12	119.8 (5)
C3—C2—C1	117.3 (5)	C8—C9—C12	119.9 (4)
C3—C2—H2	121.3	C11—C10—N4	124.6 (5)
C1—C2—H2	121.3	C11—C10—H10	117.7
C2—C3—C4	120.2 (5)	N4—C10—H10	117.7
C2—C3—H3	119.9	C10—C11—N3	117.6 (5)
C4—C3—H3	119.9	C10—C11—H11	121.2
C5—C4—C3	117.0 (4)	N3—C11—H11	121.2
C5—C4—C6	121.0 (4)	C9—C12—H12A	109.5
C3—C4—C6	122.0 (4)	C9—C12—H12B	109.5
N1—C5—C4	123.8 (5)	H12A—C12—H12B	109.5
N1—C5—H5	118.1	C9—C12—H12C	109.5
C4—C5—H5	118.1	H12A—C12—H12C	109.5
N2—C6—C7	110.9 (4)	H12B—C12—H12C	109.5
N2—C6—C4	122.4 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7···N1ⁱ	0.95	2.52	3.438 (6)	163
C10—H10···N2ⁱⁱ	0.95	2.60	3.484 (7)	156

Symmetry codes: (i) −x+1, −y+2, −z+2; (ii) −x+5/2, y+1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₁₂H₉BrN₄
M_r	289.14
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	100
a, b, c (Å)	3.9007 (14), 13.545 (5), 20.673 (8)
β (°)	93.059 (5)
V (Å³)	1090.7 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	3.75
Crystal size (mm)	0.27 × 0.11 × 0.05

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.431, 0.835
No. of measured, independent and observed [I > 2σ(I)] reflections	19939, 2668, 1887
R_int	0.085
(sin θ/λ)_max (Å⁻¹)	0.676

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.057, 0.154, 1.05
No. of reflections	2668
No. of parameters	155
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.23, −1.30

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7···N1ⁱ	0.95	2.52	3.438 (6)	163
C10—H10···N2ⁱⁱ	0.95	2.60	3.484 (7)	156

Symmetry codes: (i) −x+1, −y+2, −z+2; (ii) −x+5/2, y+1/2, −z+3/2.

References

Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Lumma, W. C. Jr & Springer, J. P. (1981). J. Org. Chem. 46, 3735–3736. CSD CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 66| Part 7| July 2010| Page o1723

doi:10.1107/S1600536810022993

Open

access