organic compounds
2-(6-Bromo-3-pyridyl)-8-methylimidazo[1,2-a]pyrazine
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
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
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Refinement
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Data collection: APEX2 (Bruker, 2007); cell 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
10.1107/S1600536810022993/hb5478sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536810022993/hb5478Isup2.hkl
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
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.
All H atoms were placed in geometrically calculated positions (C—H 0.95 Å for aromatic and 0.98 Å for methyl H atoms, respectively) and included in the
in riding motion approximation. The Uiso(H) were set to 1.2Ueq of the carrying atom (1.5Ueq for methyl H atoms). The maximum residual density peak 1.23 e/Å3 is located at a distance of 0.99 Å from the Br1 atom; the deepest hole -1.30 e/Å3 is at a distance of 0.78 Å from the Br1 atom.Data collection: APEX2 (Bruker, 2007); cell
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).Fig. 1. Molecular structure of the title compound, showing 50% probability displacement ellipsoids. H atoms are drawn as circles of arbitrary small radius. |
C12H9BrN4 | F(000) = 576 |
Mr = 289.14 | Dx = 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 |
Bruker APEXII CCD diffractometer | 2668 independent reflections |
Radiation source: fine-focus sealed tube | 1887 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.085 |
ϕ and ω scans | θmax = 28.7°, θmin = 1.8° |
Absorption correction: multi-scan (SADABS; Bruker, 2001) | h = −5→5 |
Tmin = 0.431, Tmax = 0.835 | k = −17→17 |
19939 measured reflections | l = −27→26 |
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(Fo2) + (0.0701P)2 + 3.9758P] where P = (Fo2 + 2Fc2)/3 |
2668 reflections | (Δ/σ)max = 0.001 |
155 parameters | Δρmax = 1.23 e Å−3 |
0 restraints | Δρmin = −1.30 e Å−3 |
C12H9BrN4 | V = 1090.7 (7) Å3 |
Mr = 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)° |
Bruker APEXII CCD diffractometer | 2668 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2001) | 1887 reflections with I > 2σ(I) |
Tmin = 0.431, Tmax = 0.835 | Rint = 0.085 |
19939 measured reflections |
R[F2 > 2σ(F2)] = 0.057 | 0 restraints |
wR(F2) = 0.154 | H-atom parameters constrained |
S = 1.05 | Δρmax = 1.23 e Å−3 |
2668 reflections | Δρmin = −1.30 e Å−3 |
155 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
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* |
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) |
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) |
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 |
Mr | 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) |
Tmin, Tmax | 0.431, 0.835 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 19939, 2668, 1887 |
Rint | 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 |
Δρmax, Δρmin (e Å−3) | 1.23, −1.30 |
Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
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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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.