PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2557.
Published online 2009 September 26. doi:  10.1107/S1600536809038173
PMCID: PMC2970374

N-{4-[3-(4-Fluoro­phen­yl)pyrido[2,3-b]pyrazin-2-yl]-2-pyrid­yl}isopropyl­amine

Abstract

In the crystal structure of the title compound, C21H18FN5, the pyridopyrazine ring system forms dihedral angles of 33.27 (7) and 48.69 (9)° with the 4-fluoro­phenyl and pyridine ring, respectively. The dihedral angle of the 4-fluoro­phenyl and pyridine rings is 57.45 (8)°. The crystal packing is characterized by an inter­molecular N—H(...)N hydrogen bond.

Related literature

For the preparation of pyridopyrazines under microwave conditions, see: Zhao et al. (2004 [triangle])

An external file that holds a picture, illustration, etc.
Object name is e-65-o2557-scheme1.jpg

Experimental

Crystal data

  • C21H18FN5
  • M r = 359.40
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2557-efi1.jpg
  • a = 12.042 (1) Å
  • b = 7.6586 (2) Å
  • c = 20.095 (2) Å
  • β = 100.215 (5)°
  • V = 1823.8 (3) Å3
  • Z = 4
  • Cu Kα radiation
  • μ = 0.72 mm−1
  • T = 193 K
  • 0.50 × 0.20 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971 [triangle]) T min = 0.743, T max = 0.998
  • 3578 measured reflections
  • 3468 independent reflections
  • 2912 reflections with I > 2σ(I)
  • R int = 0.063
  • 3 standard reflections frequency: 60 min intensity decay: 2%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.047
  • wR(F 2) = 0.127
  • S = 1.05
  • 3468 reflections
  • 247 parameters
  • H-atom parameters constrained
  • Δρmax = 0.29 e Å−3
  • Δρmin = −0.28 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 [triangle]); program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: PLATON.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809038173/im2142sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809038173/im2142Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

The title compound, {4-[3-(4-fluorophenyl)-pyrido[2,3-b]pyrazin-2-yl]-pyridin-2-yl}-isopropylamine (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-(2-(isopropylamino)-pyridin-4-yl)ethane-1,2-dione and 2,3-diaminopyridine yields two regioisomers, {4-[3-(4-fluorophenyl)-pyrido[2,3-b]pyrazin-2-yl]-pyridin-2-yl}-isopropylamine (I) and {4-[2-(4-fluorophenyl)-pyrido[3,2-b]pyrazin-3-yl]-pyridin-2-yl}-isopropylamine (II). The isomers were separated by flash-chromatography. To identify the two regioisomers X-ray crystallography was used. Herein we present the X-ray crystallographic 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 1). The pyridopyrazine ring encloses dihedral angles of 33.27 (7)° and 48.69 (9)° to the 4-fluorophenyl ring and the pyridine ring, respectively. The dihedral angle of the 4-fluorophenyl ring and the pyridine ring measures to 57.45 (8)° to the pyridine ring. The crystal packing is characterized by an intermolecular hydrogen bond N17–H17···N6 2.32 Å.

Experimental

1-(4-Fluorophenyl)-2-(2-(isopropylamino)pyridin-4-yl)ethane-1,2-dione (115 mg, 0.4 mmol), 2,3-diaminopyridine (44 mg, 0.4 mmol), and methanol/glacial acetic acid (3 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). Then 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, light petroleum /ethyl acetate 1:1 to 1:4) to yield 46 mg (33%) of I as a yellow solid. Suitable crystals of compound I for X-ray diffraction were obtained from a solution in n-hexane - diethyl ether (2:1) by slow evaporation of the solvent at 298 K.

Refinement

Hydrogen atoms attached to carbons were placed at calculated positions with C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp3 C-atom). Hydrogen atom attached to N17 was located in diff. Fourier maps. All H atoms were refined in the riding-model approximation with isotropic displacement parameters (set at 1.2–1.5 times of the Ueq of the parent atom).

Figures

Fig. 1.
View of compound I. Displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C21H18FN5F(000) = 752
Mr = 359.40Dx = 1.309 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 12.042 (1) Åθ = 60–69°
b = 7.6586 (2) ŵ = 0.72 mm1
c = 20.095 (2) ÅT = 193 K
β = 100.215 (5)°Plate, yellow
V = 1823.8 (3) Å30.50 × 0.20 × 0.10 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer2912 reflections with I > 2σ(I)
Radiation source: rotating anodeRint = 0.063
graphiteθmax = 70.2°, θmin = 3.7°
ω/2θ scansh = −14→14
Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971)k = −9→0
Tmin = 0.743, Tmax = 0.998l = 0→24
3578 measured reflections3 standard reflections every 60 min
3468 independent reflections intensity decay: 2%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.047H-atom parameters constrained
wR(F2) = 0.127w = 1/[σ2(Fo2) + (0.065P)2 + 0.5513P] where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
3468 reflectionsΔρmax = 0.29 e Å3
247 parametersΔρmin = −0.28 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0038 (4)

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)

xyzUiso*/Ueq
F10.34953 (12)0.36820 (19)0.45738 (6)0.0682 (4)
N10.47943 (11)0.38937 (19)0.08886 (7)0.0343 (3)
C20.43429 (13)0.4033 (2)0.14386 (8)0.0292 (3)
C30.50235 (12)0.38498 (19)0.21015 (8)0.0278 (3)
N40.61263 (11)0.36734 (17)0.21777 (7)0.0315 (3)
C50.66035 (13)0.3611 (2)0.16141 (8)0.0319 (4)
N60.77471 (11)0.3488 (2)0.17218 (8)0.0412 (4)
C70.82147 (15)0.3384 (3)0.11753 (10)0.0463 (5)
H70.90140.33150.12370.056*
C80.76109 (16)0.3370 (3)0.05108 (10)0.0508 (5)
H80.79980.32580.01400.061*
C90.64671 (16)0.3516 (3)0.04001 (9)0.0470 (5)
H90.60420.3522−0.00460.056*
C100.59296 (14)0.3660 (2)0.09677 (8)0.0336 (4)
C110.31151 (12)0.4444 (2)0.13098 (7)0.0287 (3)
C120.23734 (13)0.3532 (2)0.08126 (8)0.0349 (4)
H120.26280.25710.05810.042*
C130.12700 (13)0.4069 (2)0.06713 (8)0.0370 (4)
H130.07720.34420.03360.044*
N140.08393 (10)0.54181 (18)0.09720 (7)0.0345 (3)
C150.15497 (13)0.6273 (2)0.14529 (8)0.0307 (3)
C160.26989 (12)0.5820 (2)0.16339 (8)0.0299 (3)
H160.31810.64560.19750.036*
N170.11431 (11)0.76489 (19)0.17634 (7)0.0382 (4)
H170.15870.81530.21290.046*
C18−0.00040 (14)0.8299 (2)0.15770 (9)0.0393 (4)
H18−0.05310.72790.15130.047*
C19−0.02796 (18)0.9414 (3)0.21535 (11)0.0545 (5)
H19A−0.02580.86870.25570.082*
H19B−0.10350.99170.20220.082*
H19C0.02761.03560.22520.082*
C20−0.0150 (2)0.9323 (3)0.09207 (11)0.0610 (6)
H20A0.03071.03880.09890.091*
H20B−0.09470.96360.07800.091*
H20C0.00940.86070.05690.091*
C210.45692 (13)0.3816 (2)0.27448 (8)0.0295 (3)
C220.52397 (14)0.4499 (2)0.33258 (8)0.0355 (4)
H220.59530.49940.32960.043*
C230.48813 (17)0.4467 (2)0.39438 (9)0.0439 (4)
H230.53300.49550.43370.053*
C240.38569 (17)0.3708 (3)0.39702 (9)0.0441 (4)
C250.31854 (15)0.2973 (2)0.34194 (9)0.0410 (4)
H250.24910.24330.34600.049*
C260.35451 (14)0.3039 (2)0.28003 (8)0.0342 (4)
H260.30880.25490.24110.041*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
F10.0892 (9)0.0835 (9)0.0395 (6)−0.0090 (7)0.0321 (6)0.0019 (6)
N10.0320 (7)0.0395 (8)0.0321 (7)0.0079 (6)0.0075 (5)0.0045 (6)
C20.0298 (8)0.0263 (7)0.0321 (8)0.0022 (6)0.0070 (6)0.0014 (6)
C30.0282 (7)0.0230 (7)0.0322 (8)0.0009 (6)0.0054 (6)0.0008 (6)
N40.0285 (7)0.0311 (7)0.0348 (7)0.0033 (5)0.0053 (5)0.0024 (5)
C50.0292 (8)0.0277 (8)0.0399 (9)0.0037 (6)0.0091 (6)0.0051 (6)
N60.0275 (7)0.0448 (9)0.0524 (9)0.0048 (6)0.0103 (6)0.0048 (7)
C70.0305 (8)0.0486 (11)0.0634 (12)0.0084 (8)0.0181 (8)0.0125 (9)
C80.0460 (10)0.0590 (12)0.0540 (11)0.0162 (9)0.0273 (9)0.0193 (9)
C90.0438 (10)0.0610 (12)0.0395 (9)0.0169 (9)0.0164 (8)0.0154 (9)
C100.0324 (8)0.0325 (8)0.0373 (8)0.0085 (6)0.0101 (6)0.0074 (7)
C110.0279 (7)0.0302 (8)0.0285 (7)0.0022 (6)0.0066 (6)0.0025 (6)
C120.0333 (8)0.0360 (9)0.0363 (8)0.0011 (7)0.0085 (6)−0.0077 (7)
C130.0306 (8)0.0409 (9)0.0386 (9)−0.0044 (7)0.0037 (7)−0.0099 (7)
N140.0259 (6)0.0389 (8)0.0383 (7)0.0003 (5)0.0045 (5)−0.0038 (6)
C150.0288 (7)0.0327 (8)0.0311 (7)0.0017 (6)0.0073 (6)0.0008 (6)
C160.0276 (7)0.0307 (8)0.0305 (7)0.0006 (6)0.0026 (6)−0.0011 (6)
N170.0308 (7)0.0410 (8)0.0409 (8)0.0088 (6)0.0018 (6)−0.0093 (6)
C180.0299 (8)0.0371 (9)0.0503 (10)0.0077 (7)0.0057 (7)−0.0037 (8)
C190.0490 (11)0.0553 (12)0.0597 (12)0.0199 (9)0.0104 (9)−0.0105 (10)
C200.0668 (14)0.0562 (13)0.0567 (13)0.0236 (11)0.0025 (10)0.0048 (10)
C210.0318 (8)0.0264 (8)0.0306 (8)0.0049 (6)0.0068 (6)0.0033 (6)
C220.0389 (9)0.0327 (8)0.0344 (8)−0.0004 (7)0.0051 (7)0.0014 (7)
C230.0570 (11)0.0424 (10)0.0310 (8)−0.0020 (8)0.0044 (8)−0.0006 (7)
C240.0588 (11)0.0448 (10)0.0323 (9)0.0049 (9)0.0183 (8)0.0058 (7)
C250.0415 (9)0.0400 (9)0.0446 (10)0.0005 (8)0.0163 (7)0.0077 (8)
C260.0351 (8)0.0320 (8)0.0360 (8)0.0019 (7)0.0076 (6)0.0015 (7)

Geometric parameters (Å, °)

F1—C241.3595 (19)C15—N171.359 (2)
N1—C21.3197 (19)C15—C161.410 (2)
N1—C101.360 (2)C16—H160.9500
C2—C31.442 (2)N17—C181.454 (2)
C2—C111.489 (2)N17—H170.9144
C3—N41.3165 (19)C18—C201.518 (3)
C3—C211.491 (2)C18—C191.523 (2)
N4—C51.359 (2)C18—H181.0000
C5—N61.359 (2)C19—H19A0.9800
C5—C101.405 (2)C19—H19B0.9800
N6—C71.322 (2)C19—H19C0.9800
C7—C81.403 (3)C20—H20A0.9800
C7—H70.9500C20—H20B0.9800
C8—C91.360 (3)C20—H20C0.9800
C8—H80.9500C21—C261.391 (2)
C9—C101.412 (2)C21—C221.398 (2)
C9—H90.9500C22—C231.385 (2)
C11—C161.379 (2)C22—H220.9500
C11—C121.403 (2)C23—C241.373 (3)
C12—C131.372 (2)C23—H230.9500
C12—H120.9500C24—C251.370 (3)
C13—N141.346 (2)C25—C261.389 (2)
C13—H130.9500C25—H250.9500
N14—C151.342 (2)C26—H260.9500
C2—N1—C10117.88 (13)C15—N17—C18123.40 (14)
N1—C2—C3120.98 (14)C15—N17—H17119.3
N1—C2—C11114.55 (13)C18—N17—H17117.2
C3—C2—C11124.44 (13)N17—C18—C20111.07 (15)
N4—C3—C2120.92 (14)N17—C18—C19108.76 (15)
N4—C3—C21114.53 (13)C20—C18—C19111.33 (16)
C2—C3—C21124.54 (13)N17—C18—H18108.5
C3—N4—C5118.27 (13)C20—C18—H18108.5
N4—C5—N6115.86 (14)C19—C18—H18108.5
N4—C5—C10120.63 (14)C18—C19—H19A109.5
N6—C5—C10123.51 (15)C18—C19—H19B109.5
C7—N6—C5116.14 (15)H19A—C19—H19B109.5
N6—C7—C8124.47 (16)C18—C19—H19C109.5
N6—C7—H7117.8H19A—C19—H19C109.5
C8—C7—H7117.8H19B—C19—H19C109.5
C9—C8—C7119.59 (17)C18—C20—H20A109.5
C9—C8—H8120.2C18—C20—H20B109.5
C7—C8—H8120.2H20A—C20—H20B109.5
C8—C9—C10118.05 (17)C18—C20—H20C109.5
C8—C9—H9121.0H20A—C20—H20C109.5
C10—C9—H9121.0H20B—C20—H20C109.5
N1—C10—C5121.04 (14)C26—C21—C22118.82 (15)
N1—C10—C9120.74 (15)C26—C21—C3122.93 (14)
C5—C10—C9118.19 (15)C22—C21—C3118.12 (14)
C16—C11—C12118.58 (14)C23—C22—C21121.09 (16)
C16—C11—C2120.82 (14)C23—C22—H22119.5
C12—C11—C2120.37 (14)C21—C22—H22119.5
C13—C12—C11117.96 (15)C24—C23—C22117.83 (16)
C13—C12—H12121.0C24—C23—H23121.1
C11—C12—H12121.0C22—C23—H23121.1
N14—C13—C12124.99 (15)F1—C24—C25118.57 (17)
N14—C13—H13117.5F1—C24—C23118.20 (17)
C12—C13—H13117.5C25—C24—C23123.23 (16)
C15—N14—C13116.76 (13)C24—C25—C26118.40 (16)
N14—C15—N17118.24 (14)C24—C25—H25120.8
N14—C15—C16122.48 (14)C26—C25—H25120.8
N17—C15—C16119.27 (14)C25—C26—C21120.58 (16)
C11—C16—C15119.22 (14)C25—C26—H26119.7
C11—C16—H16120.4C21—C26—H26119.7
C15—C16—H16120.4
C10—N1—C2—C3−3.3 (2)C2—C11—C12—C13−174.10 (15)
C10—N1—C2—C11174.81 (14)C11—C12—C13—N140.3 (3)
N1—C2—C3—N45.3 (2)C12—C13—N14—C15−1.1 (3)
C11—C2—C3—N4−172.55 (14)C13—N14—C15—N17179.56 (15)
N1—C2—C3—C21−173.81 (14)C13—N14—C15—C161.1 (2)
C11—C2—C3—C218.3 (2)C12—C11—C16—C15−0.5 (2)
C2—C3—N4—C5−2.1 (2)C2—C11—C16—C15174.11 (14)
C21—C3—N4—C5177.08 (13)N14—C15—C16—C11−0.4 (2)
C3—N4—C5—N6177.84 (14)N17—C15—C16—C11−178.81 (15)
C3—N4—C5—C10−2.6 (2)N14—C15—N17—C18−3.3 (2)
N4—C5—N6—C7178.44 (16)C16—C15—N17—C18175.18 (15)
C10—C5—N6—C7−1.1 (2)C15—N17—C18—C20−75.1 (2)
C5—N6—C7—C8−0.9 (3)C15—N17—C18—C19162.02 (17)
N6—C7—C8—C91.8 (3)N4—C3—C21—C26−143.17 (15)
C7—C8—C9—C10−0.7 (3)C2—C3—C21—C2636.0 (2)
C2—N1—C10—C5−1.5 (2)N4—C3—C21—C2232.6 (2)
C2—N1—C10—C9−179.42 (16)C2—C3—C21—C22−148.19 (15)
N4—C5—C10—N14.7 (2)C26—C21—C22—C23−2.3 (2)
N6—C5—C10—N1−175.85 (15)C3—C21—C22—C23−178.29 (15)
N4—C5—C10—C9−177.38 (16)C21—C22—C23—C241.4 (3)
N6—C5—C10—C92.1 (3)C22—C23—C24—F1−179.53 (16)
C8—C9—C10—N1176.83 (18)C22—C23—C24—C250.6 (3)
C8—C9—C10—C5−1.1 (3)F1—C24—C25—C26178.49 (16)
N1—C2—C11—C16−128.17 (16)C23—C24—C25—C26−1.7 (3)
C3—C2—C11—C1649.8 (2)C24—C25—C26—C210.7 (3)
N1—C2—C11—C1246.3 (2)C22—C21—C26—C251.2 (2)
C3—C2—C11—C12−135.71 (16)C3—C21—C26—C25177.00 (15)
C16—C11—C12—C130.5 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N17—H17···N6i0.912.323.166 (2)154

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2142).

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. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [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.

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography