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Acta Crystallogr Sect E Struct Rep Online. 2008 November 1; 64(Pt 11): o2222.
Published online 2008 October 31. doi:  10.1107/S1600536808034491
PMCID: PMC2959588

tert-Butyl N-benzyl-N-(4-methyl-2-pyrid­yl)carbamate

Abstract

In the crystal structure of the title compound, C18H22N2O2, the pyridine ring makes dihedral angles of 83.71 (6) and 9.2 (1)° with the phenyl ring and the carbamate plane, respectively. The phenyl ring and the carbamate plane are nearly perpendicular to one another, with a dihedral angle of 87.17 (7)°.

Related literature

For the preparation of the title compound, see: Koch et al. (2008 [triangle]). For applications of N-benzyl-2-amino­pyridines, see, for example: Laufer & Koch (2008 [triangle]); Koch et al. (2008 [triangle]); Lipinski et al. (1985 [triangle]); Miwatashi et al. (2005 [triangle]); Stevens et al. (2005 [triangle]).

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Object name is e-64-o2222-scheme1.jpg

Experimental

Crystal data

  • C18H22N2O2
  • M r = 298.38
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o2222-efi1.jpg
  • a = 5.9090 (10) Å
  • b = 9.7779 (18) Å
  • c = 14.199 (7) Å
  • α = 89.683 (13)°
  • β = 87.968 (14)°
  • γ = 83.963 (15)°
  • V = 815.3 (5) Å3
  • Z = 2
  • Cu Kα radiation
  • μ = 0.63 mm−1
  • T = 193 (2) K
  • 0.45 × 0.45 × 0.33 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: none
  • 5914 measured reflections
  • 3074 independent reflections
  • 2747 reflections with I > 2σ(I)
  • R int = 0.090
  • 3 standard reflections frequency: 60 min intensity decay: 3%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.055
  • wR(F 2) = 0.209
  • S = 1.12
  • 3074 reflections
  • 204 parameters
  • H-atom parameters constrained
  • Δρmax = 0.31 e Å−3
  • Δρmin = −0.37 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, 2003 [triangle]); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808034491/zl2149sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808034491/zl2149Isup2.hkl

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

Acknowledgments

The authors thank the EU for financial support via the Framework Project 6 ‘MACROCEPT’, part of the EU–Craft Program.

supplementary crystallographic information

Comment

N-Benzyl-2-aminopyridin-4-yl derivatives can be found in different p38 MAP kinase inhibitors, like the imidazolopyridines (Laufer & Koch 2008; Koch et al. 2008), thiazolopyridines (Miwatashi et al. 2005) or pyrazolopyridines (Stevens et al. 2005) and in histamine H2-receptor antagonists (Lipinski et al. 1985).

The title compound, tert-butyl N-benzyl-N-(4-methylpyridin-2-yl)carbamate (I), was obtaineded as an intermediate in the synthesis of 2-alkylsulfanyl-5-(2-aminopyridin-4-yl)-4-(4-fluorophenyl)imidazoles as potent p38 MAP kinase inhibitors (Laufer & Koch 2008; Koch et al. 2008).

In the crystal structure of the title compound I the pyridine ring makes dihedral angles of 83.71 (6)° and 9.2 (1)° to the phenyl ring and the carbamate plane, respectively. The phenyl ring and the carbamate plane are nearly perpendicular to one another with a dihedral angle of 87.17 (7)°. The N1—C2 bond [1.383 (2) Å] of the carbamte function is shorter than the normal N1—C16-bond [1.475 (2) Å] to the benzyl moiety, indicating the partial double bond character of the amide bond of the carbamate.

Experimental

To a solution of tert-butyl 4-methylpyridin-2-ylcarbamate (0.75 g, 3.6 mmol) in dry DMF (11 ml) was added under an argon-atmosphere sodium hydride (0.18 g, 4.5 mmol, 60% oil dispersion) at 273 K in such a manner that the temperature was kept below 278 K. The reaction mixture was kept at 273 K for 20 min followed by the addition of benzyl bromide (0.71 g, 4.1 mmol) at the same temperature. After additional stirring at 273 K for 30 min the mixture was allowed to warm to room temperature within 1 h, after which water and ethyl acetate were added. The organic layer was washed subsequently with HCl (0.1 M), sodium bicarbonate and brine, dried (sodium sulfate) and concentrated in vacuo. The residue was purified by flash-chromatography (silica gel, n-hexane/ethyl acetate 3:1) to yield 0.60 g (56%) of I as a colourless solid (Koch et al. 2008). Recrystallization from hot n-hexane/ethyl acetate afforded colourless crystals.

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). 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. H atoms are depicted as circles of arbitrary size.

Crystal data

C18H22N2O2Z = 2
Mr = 298.38F(000) = 320
Triclinic, P1Dx = 1.215 Mg m3
Hall symbol: -P 1Cu Kα radiation, λ = 1.54178 Å
a = 5.909 (1) ÅCell parameters from 25 reflections
b = 9.7779 (18) Åθ = 65–70°
c = 14.199 (7) ŵ = 0.63 mm1
α = 89.683 (13)°T = 193 K
β = 87.968 (14)°Block, yellow
γ = 83.963 (15)°0.45 × 0.45 × 0.33 mm
V = 815.3 (5) Å3

Data collection

Enraf–Nonius CAD-4 diffractometerRint = 0.090
Radiation source: rotating anodeθmax = 69.9°, θmin = 3.1°
graphiteh = −7→7
ω/2θ scansk = −11→11
5914 measured reflectionsl = −17→17
3074 independent reflections3 standard reflections every 60 min
2747 reflections with I > 2σ(I) intensity decay: 3%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.055H-atom parameters constrained
wR(F2) = 0.209w = 1/[σ2(Fo2) + (0.1082P)2 + 0.2701P] where P = (Fo2 + 2Fc2)/3
S = 1.12(Δ/σ)max < 0.001
3074 reflectionsΔρmax = 0.31 e Å3
204 parametersΔρmin = −0.37 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: 0.034 (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
N10.6712 (3)0.71560 (15)0.31250 (11)0.0319 (4)
C20.6184 (3)0.78127 (18)0.22834 (14)0.0333 (5)
O30.7015 (3)0.88142 (15)0.19760 (11)0.0464 (4)
O40.4607 (2)0.71849 (14)0.18563 (10)0.0359 (4)
C50.3936 (3)0.7575 (2)0.08933 (14)0.0347 (5)
C60.6005 (4)0.7399 (3)0.02209 (16)0.0487 (6)
H6A0.70100.81070.03480.073*
H6B0.55100.7488−0.04300.073*
H6C0.68290.64870.03110.073*
C70.2306 (4)0.6529 (3)0.06899 (18)0.0539 (6)
H7A0.18260.66360.00380.081*
H7B0.09700.66730.11200.081*
H7C0.30680.56000.07800.081*
C80.2739 (4)0.9025 (2)0.08803 (19)0.0518 (6)
H8A0.38280.96810.10160.078*
H8B0.14970.91080.13590.078*
H8C0.21190.92220.02570.078*
C90.8500 (3)0.75070 (19)0.36948 (13)0.0321 (5)
N100.8999 (3)0.66158 (17)0.43875 (12)0.0392 (5)
C111.0670 (4)0.6864 (2)0.49585 (15)0.0422 (5)
H111.10120.62380.54600.051*
C121.1917 (3)0.7972 (2)0.48605 (15)0.0405 (5)
H121.30940.81020.52800.049*
C131.1410 (3)0.8897 (2)0.41319 (14)0.0352 (5)
C140.9660 (3)0.86750 (19)0.35502 (13)0.0337 (5)
H140.92470.93050.30590.040*
C151.2734 (3)1.0119 (2)0.39721 (16)0.0434 (5)
H15A1.28411.05990.45700.065*
H15B1.19551.07470.35190.065*
H15C1.42680.98050.37230.065*
C160.5592 (3)0.59215 (19)0.33849 (14)0.0331 (5)
H16A0.39570.60930.32450.040*
H16B0.57000.57720.40730.040*
C170.6591 (3)0.46264 (18)0.28813 (13)0.0306 (4)
C180.5344 (3)0.3499 (2)0.28782 (15)0.0404 (5)
H180.38770.35630.31810.048*
C190.6209 (4)0.2281 (2)0.24390 (18)0.0492 (6)
H190.53310.15210.24410.059*
C200.8339 (4)0.2171 (2)0.19997 (16)0.0463 (6)
H200.89370.13380.17000.056*
C210.9597 (4)0.3287 (2)0.20003 (16)0.0449 (5)
H211.10610.32200.16950.054*
C220.8739 (3)0.4502 (2)0.24424 (15)0.0382 (5)
H220.96290.52560.24450.046*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0366 (8)0.0237 (8)0.0358 (9)−0.0040 (6)−0.0036 (6)0.0012 (6)
C20.0361 (9)0.0232 (9)0.0401 (10)−0.0003 (7)−0.0008 (7)−0.0005 (7)
O30.0612 (9)0.0325 (8)0.0488 (9)−0.0166 (6)−0.0133 (7)0.0106 (7)
O40.0377 (7)0.0326 (7)0.0384 (8)−0.0070 (5)−0.0082 (5)0.0039 (6)
C50.0322 (9)0.0366 (11)0.0349 (10)−0.0008 (7)−0.0054 (7)0.0024 (8)
C60.0409 (11)0.0610 (14)0.0431 (12)−0.0011 (9)0.0011 (9)−0.0060 (10)
C70.0515 (12)0.0581 (15)0.0557 (14)−0.0194 (11)−0.0143 (10)0.0072 (11)
C80.0484 (11)0.0431 (13)0.0608 (14)0.0107 (9)−0.0046 (10)0.0099 (11)
C90.0365 (9)0.0251 (9)0.0336 (10)0.0014 (7)−0.0004 (7)−0.0021 (7)
N100.0486 (9)0.0289 (9)0.0402 (9)−0.0023 (7)−0.0088 (7)0.0047 (7)
C110.0506 (11)0.0353 (11)0.0405 (11)−0.0003 (8)−0.0120 (9)0.0034 (9)
C120.0399 (10)0.0392 (11)0.0419 (11)−0.0002 (8)−0.0060 (8)−0.0039 (9)
C130.0336 (9)0.0324 (10)0.0387 (10)−0.0003 (7)0.0023 (7)−0.0060 (8)
C140.0379 (9)0.0290 (9)0.0340 (10)−0.0026 (7)−0.0004 (7)−0.0013 (8)
C150.0376 (10)0.0429 (12)0.0509 (12)−0.0095 (8)−0.0014 (8)−0.0022 (10)
C160.0338 (9)0.0273 (9)0.0380 (10)−0.0042 (7)0.0030 (7)0.0027 (8)
C170.0316 (8)0.0256 (9)0.0351 (9)−0.0043 (7)−0.0032 (7)0.0043 (7)
C180.0398 (10)0.0342 (10)0.0486 (12)−0.0117 (8)0.0006 (8)0.0005 (9)
C190.0628 (13)0.0295 (11)0.0572 (14)−0.0143 (9)−0.0015 (10)0.0012 (10)
C200.0620 (13)0.0291 (10)0.0458 (12)0.0055 (9)−0.0047 (10)−0.0037 (9)
C210.0407 (10)0.0443 (12)0.0478 (12)0.0025 (8)0.0027 (9)−0.0048 (10)
C220.0359 (9)0.0337 (10)0.0454 (12)−0.0068 (7)0.0041 (8)0.0002 (9)

Geometric parameters (Å, °)

N1—C21.383 (3)C12—C131.390 (3)
N1—C91.424 (3)C12—H120.9500
N1—C161.475 (2)C13—C141.381 (3)
C2—O31.213 (2)C13—C151.507 (3)
C2—O41.333 (2)C14—H140.9500
O4—C51.474 (2)C15—H15A0.9800
C5—C71.512 (3)C15—H15B0.9800
C5—C81.516 (3)C15—H15C0.9800
C5—C61.520 (3)C16—C171.512 (3)
C6—H6A0.9800C16—H16A0.9900
C6—H6B0.9800C16—H16B0.9900
C6—H6C0.9800C17—C221.388 (3)
C7—H7A0.9800C17—C181.389 (3)
C7—H7B0.9800C18—C191.388 (3)
C7—H7C0.9800C18—H180.9500
C8—H8A0.9800C19—C201.379 (3)
C8—H8B0.9800C19—H190.9500
C8—H8C0.9800C20—C211.383 (3)
C9—N101.331 (3)C20—H200.9500
C9—C141.403 (3)C21—C221.386 (3)
N10—C111.342 (3)C21—H210.9500
C11—C121.377 (3)C22—H220.9500
C11—H110.9500
C2—N1—C9122.86 (15)C11—C12—H12120.9
C2—N1—C16118.75 (16)C13—C12—H12120.9
C9—N1—C16117.88 (15)C14—C13—C12118.64 (18)
O3—C2—O4124.64 (19)C14—C13—C15120.26 (18)
O3—C2—N1125.50 (18)C12—C13—C15121.11 (19)
O4—C2—N1109.86 (15)C13—C14—C9119.18 (18)
C2—O4—C5120.92 (14)C13—C14—H14120.4
O4—C5—C7101.60 (15)C9—C14—H14120.4
O4—C5—C8110.50 (17)C13—C15—H15A109.5
C7—C5—C8111.09 (18)C13—C15—H15B109.5
O4—C5—C6109.95 (15)H15A—C15—H15B109.5
C7—C5—C6110.71 (19)C13—C15—H15C109.5
C8—C5—C6112.47 (17)H15A—C15—H15C109.5
C5—C6—H6A109.5H15B—C15—H15C109.5
C5—C6—H6B109.5N1—C16—C17114.19 (14)
H6A—C6—H6B109.5N1—C16—H16A108.7
C5—C6—H6C109.5C17—C16—H16A108.7
H6A—C6—H6C109.5N1—C16—H16B108.7
H6B—C6—H6C109.5C17—C16—H16B108.7
C5—C7—H7A109.5H16A—C16—H16B107.6
C5—C7—H7B109.5C22—C17—C18118.39 (18)
H7A—C7—H7B109.5C22—C17—C16122.65 (16)
C5—C7—H7C109.5C18—C17—C16118.94 (16)
H7A—C7—H7C109.5C19—C18—C17120.95 (18)
H7B—C7—H7C109.5C19—C18—H18119.5
C5—C8—H8A109.5C17—C18—H18119.5
C5—C8—H8B109.5C20—C19—C18120.19 (19)
H8A—C8—H8B109.5C20—C19—H19119.9
C5—C8—H8C109.5C18—C19—H19119.9
H8A—C8—H8C109.5C19—C20—C21119.30 (19)
H8B—C8—H8C109.5C19—C20—H20120.3
N10—C9—C14122.13 (19)C21—C20—H20120.3
N10—C9—N1113.83 (16)C20—C21—C22120.57 (19)
C14—C9—N1124.04 (17)C20—C21—H21119.7
C9—N10—C11117.88 (18)C22—C21—H21119.7
N10—C11—C12123.88 (19)C21—C22—C17120.60 (18)
N10—C11—H11118.1C21—C22—H22119.7
C12—C11—H11118.1C17—C22—H22119.7
C11—C12—C13118.26 (19)
C9—N1—C2—O3−6.7 (3)C11—C12—C13—C15−178.86 (18)
C16—N1—C2—O3−178.23 (17)C12—C13—C14—C9−1.9 (3)
C9—N1—C2—O4173.65 (15)C15—C13—C14—C9177.99 (16)
C16—N1—C2—O42.1 (2)N10—C9—C14—C131.4 (3)
O3—C2—O4—C57.6 (3)N1—C9—C14—C13−178.34 (15)
N1—C2—O4—C5−172.67 (14)C2—N1—C16—C1778.3 (2)
C2—O4—C5—C7175.46 (17)C9—N1—C16—C17−93.7 (2)
C2—O4—C5—C8−66.6 (2)N1—C16—C17—C2218.4 (3)
C2—O4—C5—C658.2 (2)N1—C16—C17—C18−163.51 (17)
C2—N1—C9—N10−169.13 (16)C22—C17—C18—C19−0.7 (3)
C16—N1—C9—N102.5 (2)C16—C17—C18—C19−178.88 (19)
C2—N1—C9—C1410.6 (3)C17—C18—C19—C200.3 (4)
C16—N1—C9—C14−177.75 (16)C18—C19—C20—C21−0.1 (4)
C14—C9—N10—C110.1 (3)C19—C20—C21—C220.4 (3)
N1—C9—N10—C11179.83 (16)C20—C21—C22—C17−0.9 (3)
C9—N10—C11—C12−1.1 (3)C18—C17—C22—C211.0 (3)
N10—C11—C12—C130.5 (3)C16—C17—C22—C21179.10 (19)
C11—C12—C13—C141.0 (3)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: ZL2149).

References

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