Abstract
In the crystal structure of the title compound, C18H11FN4, the pyridopyrazine ring makes dihedral angles of 34.67 (7) and 52.24 (7)° with the 4-fluorophenyl and pyridine rings, respectively. The 4-fluorophenyl ring makes a dihedral angle of 59.56 (9)° with the pyridine ring.
Related literature
For preparation of pyridopyrazines under microwave conditions, see: Zhao et al. (2004 ▶).
Experimental
Crystal data
C18H11FN4
M r = 302.31
Monoclinic,
a = 9.7163 (9) Å
b = 13.7937 (6) Å
c = 10.8164 (10) Å
β = 90.994 (5)°
V = 1449.4 (2) Å3
Z = 4
Cu Kα radiation
μ = 0.78 mm−1
T = 193 K
0.30 × 0.25 × 0.22 mm
Data collection
Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
2906 measured reflections
2753 independent reflections
2654 reflections with I > 2σ(I)
R int = 0.023
3 standard reflections frequency: 60 min intensity decay: 2%
Refinement
R[F 2 > 2σ(F 2)] = 0.047
wR(F 2) = 0.149
S = 1.20
2753 reflections
209 parameters
H-atom parameters constrained
Δρmax = 0.31 e Å−3
Δρmin = −0.24 e Å−3
Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.
Supplementary Material
Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809037970/bt5066sup1.cif
Structure factors: contains datablocks I. DOI: 10.1107/S1600536809037970/bt5066Isup2.hkl
supplementary crystallographic information
Comment
The title compound, 3-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[2,3-b]pyrazine (I), was prepared in the course of our studies on pyridin-4-yl-substituted pyridopyrazines as p38 mitogen-activated protein (MAP) kinase inhibitors.
The microwave-assisted reaction of 1-(4-fluorophenyl)-2-(pyridin-4-yl)ethane-1,2-dione and 2,3-diaminopyridine yields two regioisomers, 3-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[2,3-b]pyrazine (I) and 2-(4-fluorophenyl)-3-(pyridin-4-yl)pyrido[3,2-b]pyrazine (II) (Figure I). The isomers were separated by flash-chromatography. To identify the two regioisomers x-ray analysis was used. In this article we present the X-ray data of the first eluted isomer I.
As might be expected the 4-fluorophenyl, the pyridine ring as well as the pyridopyrazine ring are planar (Figure 2). The pyridopyrazine ring makes dihedral angles of 34.67 (7)° and 52.24 (7)° to the 4-fluorophenyl ring and the pyridine ring, respectively. The 4-fluorophenyl ring makes a dihedral angle of 59.56 (9)° to the pyridine ring.
Experimental
1-(4-Fluorophenyl)-2-(pyridin-4-yl)ethane-1,2-dione (113 mg, 0.5 mmol), and 2,3-diaminopyridine (54 mg, 0.5 mmol), and methanol/glacial acetic acid (2 ml, 9:1, V:V) were combined in a reaction vial. The reaction vessel was heated in a microwave reactor for 5 min at 433 K (initial power 250 W), after which a stream of compressed air cooled the reaction vessel to r.t. The solvent was removed under reduced pressure and the residue was purified by flash-chromatography (silica gel, petroleum ether/ethyl acetate 1–4 to 0–1) to yield 67 mg (44%) of I as a colorless solid. Suitable crystals of compound I for X-ray were obtained by slow evaporation at 298 K of a solution of n-hexane - diethyl ether (2–1).
Refinement
Hydrogen atoms were placed at calculated positions with C—H = 0.95 Å . They were refined in the riding-model approximation with isotropic displacement parameters set at 1.2 times of the Ueq of the parent atom.
Figures
Crystal data
C18H11FN4 | F(000) = 624 |
Mr = 302.31 | Dx = 1.385 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: -P 2ybc | Cell parameters from 25 reflections |
a = 9.7163 (9) Å | θ = 65–69° |
b = 13.7937 (6) Å | µ = 0.78 mm−1 |
c = 10.8164 (10) Å | T = 193 K |
β = 90.994 (5)° | Block, colourless |
V = 1449.4 (2) Å3 | 0.30 × 0.25 × 0.22 mm |
Z = 4 |
Data collection
Enraf–Nonius CAD-4 diffractometer | Rint = 0.023 |
Radiation source: rotating anode | θmax = 70.0°, θmin = 4.6° |
graphite | h = −11→11 |
ω/2θ scans | k = 0→16 |
2906 measured reflections | l = 0→13 |
2753 independent reflections | 3 standard reflections every 60 min |
2654 reflections with I > 2σ(I) | intensity decay: 2% |
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)] = 0.047 | H-atom parameters constrained |
wR(F2) = 0.149 | w = 1/[σ2(Fo2) + (0.073P)2 + 0.6448P] where P = (Fo2 + 2Fc2)/3 |
S = 1.20 | (Δ/σ)max < 0.001 |
2753 reflections | Δρmax = 0.31 e Å−3 |
209 parameters | Δρmin = −0.24 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: 0.0079 (9) |
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 (Å2)
x | y | z | Uiso*/Ueq | ||
C1 | 0.71724 (16) | 0.38396 (12) | 0.46833 (15) | 0.0271 (4) | |
N2 | 0.82823 (14) | 0.41887 (10) | 0.52355 (13) | 0.0300 (4) | |
C3 | 0.81675 (18) | 0.44950 (12) | 0.64285 (16) | 0.0294 (4) | |
C4 | 0.9322 (2) | 0.48632 (15) | 0.70813 (17) | 0.0383 (4) | |
H4 | 1.0203 | 0.4880 | 0.6715 | 0.046* | |
C5 | 0.9135 (2) | 0.51935 (15) | 0.82524 (18) | 0.0430 (5) | |
H5 | 0.9892 | 0.5436 | 0.8727 | 0.052* | |
C6 | 0.7806 (2) | 0.51712 (15) | 0.87511 (18) | 0.0422 (5) | |
H6 | 0.7698 | 0.5425 | 0.9560 | 0.051* | |
N7 | 0.67047 (17) | 0.48270 (12) | 0.81831 (14) | 0.0385 (4) | |
C8 | 0.68851 (18) | 0.44723 (12) | 0.70263 (15) | 0.0289 (4) | |
N9 | 0.57616 (14) | 0.40774 (11) | 0.64607 (13) | 0.0297 (4) | |
C10 | 0.58915 (16) | 0.37376 (11) | 0.53266 (15) | 0.0263 (4) | |
C11 | 0.73166 (16) | 0.36165 (12) | 0.33454 (15) | 0.0277 (4) | |
C12 | 0.64457 (18) | 0.40275 (13) | 0.24579 (16) | 0.0324 (4) | |
H12 | 0.5701 | 0.4429 | 0.2695 | 0.039* | |
C13 | 0.6681 (2) | 0.38414 (14) | 0.12271 (17) | 0.0377 (4) | |
H13 | 0.6082 | 0.4129 | 0.0629 | 0.045* | |
N14 | 0.77022 (17) | 0.32808 (12) | 0.08247 (15) | 0.0406 (4) | |
C15 | 0.85276 (19) | 0.28932 (14) | 0.16925 (18) | 0.0370 (4) | |
H15 | 0.9263 | 0.2494 | 0.1428 | 0.044* | |
C16 | 0.83866 (17) | 0.30326 (13) | 0.29441 (17) | 0.0322 (4) | |
H16 | 0.9005 | 0.2737 | 0.3520 | 0.039* | |
C17 | 0.46722 (16) | 0.32309 (12) | 0.47894 (15) | 0.0270 (4) | |
C18 | 0.48092 (17) | 0.24153 (13) | 0.40375 (16) | 0.0307 (4) | |
H18 | 0.5702 | 0.2194 | 0.3830 | 0.037* | |
C19 | 0.36587 (19) | 0.19234 (14) | 0.35891 (18) | 0.0363 (4) | |
H19 | 0.3750 | 0.1363 | 0.3086 | 0.044* | |
C20 | 0.23859 (18) | 0.22707 (15) | 0.3895 (2) | 0.0405 (5) | |
C21 | 0.21958 (18) | 0.30696 (14) | 0.4637 (2) | 0.0404 (5) | |
H21 | 0.1298 | 0.3289 | 0.4831 | 0.049* | |
C22 | 0.33549 (17) | 0.35415 (13) | 0.50905 (17) | 0.0329 (4) | |
H22 | 0.3251 | 0.4087 | 0.5617 | 0.039* | |
F23 | 0.12564 (12) | 0.17883 (11) | 0.34584 (16) | 0.0658 (5) |
Atomic displacement parameters (Å2)
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0255 (8) | 0.0238 (8) | 0.0320 (9) | 0.0011 (6) | −0.0009 (6) | 0.0019 (6) |
N2 | 0.0273 (7) | 0.0305 (7) | 0.0322 (7) | −0.0026 (6) | 0.0003 (6) | 0.0008 (6) |
C3 | 0.0308 (9) | 0.0265 (8) | 0.0307 (8) | −0.0022 (6) | −0.0022 (7) | 0.0029 (6) |
C4 | 0.0338 (9) | 0.0418 (10) | 0.0390 (10) | −0.0094 (8) | −0.0035 (7) | 0.0022 (8) |
C5 | 0.0460 (11) | 0.0450 (11) | 0.0375 (10) | −0.0158 (9) | −0.0105 (8) | 0.0024 (8) |
C6 | 0.0540 (12) | 0.0420 (11) | 0.0304 (9) | −0.0102 (9) | −0.0038 (8) | −0.0039 (8) |
N7 | 0.0420 (9) | 0.0417 (9) | 0.0320 (8) | −0.0044 (7) | 0.0009 (6) | −0.0040 (6) |
C8 | 0.0314 (8) | 0.0258 (8) | 0.0295 (8) | −0.0006 (6) | −0.0011 (6) | 0.0018 (6) |
N9 | 0.0283 (7) | 0.0307 (8) | 0.0303 (7) | −0.0004 (6) | 0.0007 (5) | −0.0001 (6) |
C10 | 0.0263 (8) | 0.0236 (8) | 0.0290 (8) | 0.0019 (6) | −0.0001 (6) | 0.0008 (6) |
C11 | 0.0243 (8) | 0.0273 (8) | 0.0315 (9) | −0.0045 (6) | 0.0026 (6) | −0.0010 (6) |
C12 | 0.0319 (9) | 0.0315 (9) | 0.0338 (9) | 0.0008 (7) | 0.0023 (7) | 0.0009 (7) |
C13 | 0.0413 (10) | 0.0387 (10) | 0.0329 (9) | −0.0040 (8) | −0.0023 (7) | 0.0012 (7) |
N14 | 0.0454 (9) | 0.0425 (9) | 0.0341 (8) | −0.0067 (7) | 0.0062 (7) | −0.0070 (7) |
C15 | 0.0324 (9) | 0.0349 (9) | 0.0441 (10) | −0.0043 (7) | 0.0090 (8) | −0.0096 (8) |
C16 | 0.0254 (8) | 0.0327 (9) | 0.0384 (9) | −0.0022 (7) | 0.0012 (7) | −0.0041 (7) |
C17 | 0.0246 (8) | 0.0279 (8) | 0.0283 (8) | −0.0010 (6) | 0.0000 (6) | 0.0035 (6) |
C18 | 0.0251 (8) | 0.0315 (9) | 0.0356 (9) | −0.0002 (7) | 0.0010 (6) | −0.0007 (7) |
C19 | 0.0341 (9) | 0.0330 (9) | 0.0418 (10) | −0.0029 (7) | −0.0028 (7) | −0.0063 (7) |
C20 | 0.0263 (9) | 0.0387 (10) | 0.0561 (12) | −0.0063 (7) | −0.0085 (8) | −0.0023 (9) |
C21 | 0.0235 (9) | 0.0386 (10) | 0.0593 (12) | 0.0021 (7) | 0.0004 (8) | −0.0008 (9) |
C22 | 0.0285 (9) | 0.0295 (9) | 0.0407 (9) | 0.0020 (7) | 0.0024 (7) | −0.0014 (7) |
F23 | 0.0305 (6) | 0.0594 (9) | 0.1070 (12) | −0.0084 (6) | −0.0157 (7) | −0.0256 (8) |
Geometric parameters (Å, °)
C1—N2 | 1.315 (2) | C12—H12 | 0.9500 |
C1—C10 | 1.443 (2) | C13—N14 | 1.336 (3) |
C1—C11 | 1.488 (2) | C13—H13 | 0.9500 |
N2—C3 | 1.364 (2) | N14—C15 | 1.336 (3) |
C3—C4 | 1.410 (2) | C15—C16 | 1.377 (3) |
C3—C8 | 1.414 (2) | C15—H15 | 0.9500 |
C4—C5 | 1.361 (3) | C16—H16 | 0.9500 |
C4—H4 | 0.9500 | C17—C22 | 1.394 (2) |
C5—C6 | 1.409 (3) | C17—C18 | 1.396 (2) |
C5—H5 | 0.9500 | C18—C19 | 1.388 (2) |
C6—N7 | 1.313 (2) | C18—H18 | 0.9500 |
C6—H6 | 0.9500 | C19—C20 | 1.372 (3) |
N7—C8 | 1.358 (2) | C19—H19 | 0.9500 |
C8—N9 | 1.356 (2) | C20—F23 | 1.361 (2) |
N9—C10 | 1.321 (2) | C20—C21 | 1.378 (3) |
C10—C17 | 1.485 (2) | C21—C22 | 1.383 (3) |
C11—C12 | 1.389 (2) | C21—H21 | 0.9500 |
C11—C16 | 1.391 (2) | C22—H22 | 0.9500 |
C12—C13 | 1.379 (3) | ||
N2—C1—C10 | 121.60 (15) | C11—C12—H12 | 120.6 |
N2—C1—C11 | 115.28 (14) | N14—C13—C12 | 123.97 (18) |
C10—C1—C11 | 123.03 (14) | N14—C13—H13 | 118.0 |
C1—N2—C3 | 117.59 (14) | C12—C13—H13 | 118.0 |
N2—C3—C4 | 120.53 (16) | C15—N14—C13 | 116.28 (16) |
N2—C3—C8 | 120.86 (15) | N14—C15—C16 | 124.50 (17) |
C4—C3—C8 | 118.60 (16) | N14—C15—H15 | 117.7 |
C5—C4—C3 | 117.99 (17) | C16—C15—H15 | 117.7 |
C5—C4—H4 | 121.0 | C15—C16—C11 | 118.40 (17) |
C3—C4—H4 | 121.0 | C15—C16—H16 | 120.8 |
C4—C5—C6 | 119.12 (17) | C11—C16—H16 | 120.8 |
C4—C5—H5 | 120.4 | C22—C17—C18 | 118.76 (15) |
C6—C5—H5 | 120.4 | C22—C17—C10 | 119.57 (15) |
N7—C6—C5 | 125.01 (18) | C18—C17—C10 | 121.58 (15) |
N7—C6—H6 | 117.5 | C19—C18—C17 | 120.87 (16) |
C5—C6—H6 | 117.5 | C19—C18—H18 | 119.6 |
C6—N7—C8 | 116.37 (16) | C17—C18—H18 | 119.6 |
N9—C8—N7 | 116.40 (15) | C20—C19—C18 | 117.97 (17) |
N9—C8—C3 | 120.75 (15) | C20—C19—H19 | 121.0 |
N7—C8—C3 | 122.84 (16) | C18—C19—H19 | 121.0 |
C10—N9—C8 | 118.18 (14) | F23—C20—C19 | 118.07 (18) |
N9—C10—C1 | 120.67 (15) | F23—C20—C21 | 118.54 (17) |
N9—C10—C17 | 116.22 (14) | C19—C20—C21 | 123.38 (17) |
C1—C10—C17 | 123.09 (14) | C20—C21—C22 | 117.80 (17) |
C12—C11—C16 | 118.06 (16) | C20—C21—H21 | 121.1 |
C12—C11—C1 | 121.39 (15) | C22—C21—H21 | 121.1 |
C16—C11—C1 | 120.45 (15) | C21—C22—C17 | 121.19 (17) |
C13—C12—C11 | 118.80 (17) | C21—C22—H22 | 119.4 |
C13—C12—H12 | 120.6 | C17—C22—H22 | 119.4 |
C10—C1—N2—C3 | −2.9 (2) | N2—C1—C11—C16 | 52.5 (2) |
C11—C1—N2—C3 | 173.66 (14) | C10—C1—C11—C16 | −130.92 (17) |
C1—N2—C3—C4 | 179.03 (16) | C16—C11—C12—C13 | −0.2 (2) |
C1—N2—C3—C8 | −2.5 (2) | C1—C11—C12—C13 | 176.03 (16) |
N2—C3—C4—C5 | 177.47 (17) | C11—C12—C13—N14 | 0.3 (3) |
C8—C3—C4—C5 | −1.0 (3) | C12—C13—N14—C15 | −0.3 (3) |
C3—C4—C5—C6 | −1.2 (3) | C13—N14—C15—C16 | 0.2 (3) |
C4—C5—C6—N7 | 1.9 (3) | N14—C15—C16—C11 | −0.1 (3) |
C5—C6—N7—C8 | −0.2 (3) | C12—C11—C16—C15 | 0.1 (2) |
C6—N7—C8—N9 | 177.15 (16) | C1—C11—C16—C15 | −176.17 (15) |
C6—N7—C8—C3 | −2.2 (3) | N9—C10—C17—C22 | 34.0 (2) |
N2—C3—C8—N9 | 5.1 (2) | C1—C10—C17—C22 | −147.77 (17) |
C4—C3—C8—N9 | −176.46 (16) | N9—C10—C17—C18 | −142.59 (16) |
N2—C3—C8—N7 | −175.65 (16) | C1—C10—C17—C18 | 35.6 (2) |
C4—C3—C8—N7 | 2.8 (3) | C22—C17—C18—C19 | 0.4 (3) |
N7—C8—N9—C10 | 179.00 (15) | C10—C17—C18—C19 | 177.00 (16) |
C3—C8—N9—C10 | −1.7 (2) | C17—C18—C19—C20 | 0.8 (3) |
C8—N9—C10—C1 | −3.8 (2) | C18—C19—C20—F23 | −179.86 (17) |
C8—N9—C10—C17 | 174.53 (14) | C18—C19—C20—C21 | −1.1 (3) |
N2—C1—C10—N9 | 6.4 (2) | F23—C20—C21—C22 | 178.90 (18) |
C11—C1—C10—N9 | −169.95 (15) | C19—C20—C21—C22 | 0.1 (3) |
N2—C1—C10—C17 | −171.78 (15) | C20—C21—C22—C17 | 1.1 (3) |
C11—C1—C10—C17 | 11.9 (2) | C18—C17—C22—C21 | −1.4 (3) |
N2—C1—C11—C12 | −123.57 (17) | C10—C17—C22—C21 | −178.07 (16) |
C10—C1—C11—C12 | 53.0 (2) |
Footnotes
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5066).
References
- Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst.32, 115–119.
- Dräger, M. & Gattow, G. (1971). Acta Chem. Scand.25, 761–762.
- Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
- Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [DOI] [PubMed]
- Spek, A. L. (2009). Acta Cryst. D65, 148–155. [DOI] [PMC free article] [PubMed]
- Zhao, Z., Wisnoski, D. D., Wolkenberg, S. E., Leister, W. H., Wang, Y. & Lindsley, C. W. (2004). Tetrahedron Lett.45, 4873–4876.
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809037970/bt5066sup1.cif
Structure factors: contains datablocks I. DOI: 10.1107/S1600536809037970/bt5066Isup2.hkl