supplementary materials


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Acta Cryst. (2013). E69, o1810    [ doi:10.1107/S160053681303153X ]

Methyl N-(3-cyano­picolino­yl)-L-tryptophanate

O. Ovdiichuk, O. Hordiyenko, Z. Voitenko, A. Arrault and V. Medviediev

Abstract top

In the title compound, C19H16N4O3, the stereocenter has an L configuration; L-tryptophan methyl ester hydro­chloride being used as a starting material. The indole ring system and the pyridine ring are inclined to one another by 13.55 (14)°. In the crystal, adjacent mol­ecules are linked via N-H...O hydrogen bonds, forming chains propagating along the c-axis direction.

Comment top

Cyano substituted compounds like the title compound are useful as intermediates in the synthesis of N-hydroxybenzamidines (Peterlin-Mašič & Kikelj, 2001). Substituted N-hydroxybenzamidines as well as their heterocyclic analogs are key intermediates in the synthesis of pharmaceutically important derivatives of 1,2,4-oxadiazole. The latter are well known for their anticancer (Kundu et al., 2012), anti-HIV (Sakamoto et al., 2007), and anti-microbial activities (Tyrkov & Sukhenko, 2004). In our studies on N-hydroxyamidines, of a heterocyclic nature from corresponding cyano derivatives, we synthesized the title compound and report herein on its crystal structure.

The molecular structure of the title compound is illustrated in Fig. 1. The stereo center, C8, has an L-configuration similar to the starting material L-tryptophan methyl ester hydrochloride. The dihedral angle between the indole ring system (N4/C12-C19; maximum deviation 0.033 (3) Å for atom C15) and pyridine ring (N1/C1-C4/C6) is 13.55 (14)°.

In the crystal, adjacent molecules are linked via N—H···O hydrogen bonds, forming chains propagating along the c axis direction (Table 1).

Related literature top

Cyano-substituted compounds, like the title compound, are useful as intermediates in the synthesis of N-hydroxybenzamidines, see: Peterlin-Mašič & Kikelj (2001). For the synthesis of the title compound, see: Devillers et al. (2002). For the biological activity of 1,2,4-oxadiazole derivatives, see: Kundu et al. (2012); Sakamoto et al. (2007); Tyrkov & Sukhenko (2004).

Experimental top

The title compound was synthesized according to the literature procedure (Devillers et al., 2002). 2-Cyanonicotinic acid (5 mmol) was dissolved in CH2Cl2 (30 ml), then triethylamine (10 mmol), L-tryptophan methyl ester hydrochloride (5 mmol) and N-hydroxybenzotriazole (5 mmol) were added to the solution. The mixture was stirred at 273 K and EDCI (5.05 mmol; 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydroiodide) was added. Then, the mixture was stirred at room temperature over night. The residue was diluted in CH2Cl2, washed with a solution of 0.1M HCl (3 × 15 ml), brine (20 ml) and then dried over MgSO4 and concentrated under vacuo. The solid obtained was purified by column chromatography (CH2Cl2:MeOH 94:6). The title compound is a byproduct and crystallized as pale-yellow block-like crystals, suitable for X-ray diffraction analysis, by slow evaporation of a solution in dichloromethane and methanol (9:1).

Refinement top

All H atoms were placed in idealized positions and constrained to ride on their parent atoms: N-H = 0.86 Å, C-H = 0.93, 0.98, 0.97 and 0.96 Å for H(aromatic), methine, methylene and methyl H atoms, respectively, with Uiso = 1.5Ueq(C-methyl) and = 1.2Ueq(N,C) for other H atoms.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
Methyl N-(3-cyanopicolinoyl)-L-tryptophanate top
Crystal data top
C19H16N4O3F(000) = 364
Mr = 348.36Dx = 1.338 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.7107 Å
Hall symbol: P 2ybCell parameters from 1601 reflections
a = 7.473 (2) Åθ = 3.2–32.1°
b = 11.977 (4) ŵ = 0.09 mm1
c = 9.661 (3) ÅT = 293 K
β = 91.01 (2)°Block, colourless
V = 864.6 (4) Å30.34 × 0.29 × 0.21 mm
Z = 2
Data collection top
Agilent Xcalibur Sapphire3
diffractometer
4832 independent reflections
Radiation source: Enhance (Mo) X-ray Source2596 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.047
Detector resolution: 16.1827 pixels mm-1θmax = 30.0°, θmin = 3.2°
ω scansh = 1010
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
k = 1616
Tmin = 0.753, Tmax = 1.000l = 1313
9857 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.051H-atom parameters constrained
wR(F2) = 0.133 w = 1/[σ2(Fo2) + (0.0481P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.93(Δ/σ)max = 0.002
4832 reflectionsΔρmax = 0.20 e Å3
236 parametersΔρmin = 0.14 e Å3
1 restraintAbsolute structure: Flack parameter determined using 855 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
64 constraintsAbsolute structure parameter: 0.001 (3)
Primary atom site location: structure-invariant direct methods
Crystal data top
C19H16N4O3V = 864.6 (4) Å3
Mr = 348.36Z = 2
Monoclinic, P21Mo Kα radiation
a = 7.473 (2) ŵ = 0.09 mm1
b = 11.977 (4) ÅT = 293 K
c = 9.661 (3) Å0.34 × 0.29 × 0.21 mm
β = 91.01 (2)°
Data collection top
Agilent Xcalibur Sapphire3
diffractometer
4832 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
2596 reflections with I > 2σ(I)
Tmin = 0.753, Tmax = 1.000Rint = 0.047
9857 measured reflectionsθmax = 30.0°
Refinement top
R[F2 > 2σ(F2)] = 0.051H-atom parameters constrained
wR(F2) = 0.133Δρmax = 0.20 e Å3
S = 0.93Δρmin = 0.14 e Å3
4832 reflectionsAbsolute structure: Flack parameter determined using 855 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
236 parametersAbsolute structure parameter: 0.001 (3)
1 restraint
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.3366 (4)0.9180 (2)0.4295 (2)0.0820 (8)
O20.0128 (4)1.0476 (3)0.1272 (4)0.0933 (9)
O30.1275 (3)1.2086 (2)0.1722 (3)0.0744 (8)
N10.2235 (4)0.7036 (2)0.1931 (3)0.0593 (7)
N20.4469 (6)0.7467 (3)0.6623 (4)0.0918 (12)
N30.2808 (4)0.9245 (2)0.2012 (3)0.0588 (7)
H30.25530.88650.12800.071*
N40.3014 (4)0.9839 (3)0.2741 (3)0.0649 (8)
H40.28700.93430.33760.078*
C10.2040 (5)0.5917 (3)0.1847 (4)0.0733 (11)
H10.15870.56150.10260.088*
C20.2477 (5)0.5201 (3)0.2913 (5)0.0779 (12)
H20.23440.44340.28020.094*
C30.3103 (5)0.5626 (4)0.4126 (4)0.0710 (10)
H3A0.34040.51560.48600.085*
C40.3291 (4)0.6783 (3)0.4258 (3)0.0565 (9)
C50.3958 (5)0.7217 (3)0.5548 (4)0.0692 (10)
C60.2835 (4)0.7458 (3)0.3133 (3)0.0540 (8)
C70.3022 (5)0.8708 (3)0.3205 (3)0.0544 (8)
C80.2987 (4)1.0447 (3)0.1894 (3)0.0534 (8)
H80.34461.07310.27830.064*
C90.1191 (5)1.0983 (3)0.1613 (3)0.0576 (9)
C100.0323 (6)1.2707 (4)0.1397 (6)0.0924 (15)
H10A0.07861.24790.05080.139*
H10B0.00491.34900.13770.139*
H10C0.12011.25670.20890.139*
C110.4336 (5)1.0773 (3)0.0766 (3)0.0611 (9)
H11A0.46581.15510.08950.073*
H11B0.54141.03330.09060.073*
C120.3694 (4)1.0617 (3)0.0696 (3)0.0555 (8)
C130.3676 (5)0.9647 (3)0.1435 (3)0.0628 (9)
H130.40580.89570.11000.075*
C140.2617 (5)1.0954 (3)0.2872 (3)0.0558 (9)
C150.3002 (4)1.1473 (3)0.1602 (3)0.0521 (8)
C160.2762 (5)1.2624 (3)0.1484 (4)0.0651 (10)
H160.30161.29870.06530.078*
C170.2146 (6)1.3211 (3)0.2616 (5)0.0776 (12)
H170.19901.39790.25460.093*
C180.1748 (5)1.2681 (4)0.3863 (5)0.0800 (12)
H180.13241.30990.46100.096*
C190.1972 (5)1.1552 (4)0.4010 (3)0.0680 (10)
H190.17011.11970.48430.082*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.138 (2)0.0690 (16)0.0390 (13)0.0108 (16)0.0117 (14)0.0018 (12)
O20.0744 (18)0.0795 (19)0.125 (3)0.0159 (16)0.0208 (17)0.0269 (18)
O30.0749 (18)0.0649 (16)0.0831 (18)0.0101 (13)0.0101 (13)0.0138 (13)
N10.0617 (18)0.0628 (18)0.0533 (18)0.0036 (14)0.0028 (14)0.0073 (14)
N20.136 (3)0.090 (2)0.0489 (19)0.045 (2)0.0133 (19)0.0005 (18)
N30.0815 (19)0.0571 (17)0.0374 (15)0.0026 (15)0.0072 (13)0.0031 (12)
N40.088 (2)0.0628 (18)0.0445 (17)0.0164 (16)0.0091 (14)0.0101 (14)
C10.074 (3)0.071 (3)0.074 (3)0.003 (2)0.008 (2)0.014 (2)
C20.075 (3)0.060 (2)0.099 (4)0.0003 (19)0.003 (2)0.002 (2)
C30.072 (2)0.067 (2)0.074 (3)0.010 (2)0.004 (2)0.012 (2)
C40.0557 (19)0.063 (2)0.051 (2)0.0115 (15)0.0030 (15)0.0044 (16)
C50.087 (3)0.066 (2)0.054 (2)0.026 (2)0.0042 (19)0.0076 (19)
C60.0508 (19)0.064 (2)0.0478 (19)0.0073 (16)0.0032 (14)0.0031 (16)
C70.063 (2)0.064 (2)0.0362 (18)0.0110 (16)0.0013 (15)0.0013 (15)
C80.069 (2)0.0526 (19)0.0380 (16)0.0012 (16)0.0088 (14)0.0014 (15)
C90.061 (2)0.065 (2)0.0465 (18)0.0050 (17)0.0004 (15)0.0072 (16)
C100.079 (3)0.084 (3)0.114 (4)0.028 (2)0.002 (2)0.002 (3)
C110.064 (2)0.066 (2)0.0531 (19)0.0022 (18)0.0010 (15)0.0000 (17)
C120.0613 (19)0.0580 (19)0.0474 (17)0.0095 (17)0.0079 (14)0.0039 (16)
C130.079 (2)0.058 (2)0.051 (2)0.0090 (18)0.0086 (17)0.0012 (17)
C140.060 (2)0.061 (2)0.0473 (18)0.0087 (16)0.0130 (15)0.0006 (16)
C150.0559 (18)0.0554 (19)0.0454 (17)0.0082 (16)0.0117 (14)0.0022 (16)
C160.073 (2)0.061 (2)0.062 (2)0.0071 (18)0.0122 (18)0.0032 (19)
C170.080 (3)0.067 (2)0.087 (3)0.003 (2)0.021 (2)0.005 (2)
C180.080 (3)0.092 (3)0.069 (3)0.009 (2)0.015 (2)0.018 (2)
C190.071 (2)0.088 (3)0.0456 (19)0.007 (2)0.0086 (16)0.0029 (19)
Geometric parameters (Å, º) top
O1—C71.219 (4)C8—H80.9800
O2—C91.199 (4)C8—C91.507 (5)
O3—C91.327 (4)C8—C111.547 (4)
O3—C101.437 (5)C10—H10A0.9600
N1—C11.351 (5)C10—H10B0.9600
N1—C61.337 (4)C10—H10C0.9600
N2—C51.141 (5)C11—H11A0.9700
N3—H30.8600C11—H11B0.9700
N3—C71.327 (4)C11—C121.495 (5)
N3—C81.451 (4)C12—C131.364 (5)
N4—H40.8600C12—C151.438 (5)
N4—C131.366 (4)C13—H130.9300
N4—C141.374 (5)C14—C151.401 (4)
C1—H10.9300C14—C191.391 (5)
C1—C21.375 (6)C15—C161.394 (5)
C2—H20.9300C16—H160.9300
C2—C31.354 (6)C16—C171.372 (6)
C3—H3A0.9300C17—H170.9300
C3—C41.399 (6)C17—C181.389 (6)
C4—C51.431 (5)C18—H180.9300
C4—C61.392 (5)C18—C191.370 (6)
C6—C71.505 (5)C19—H190.9300
C9—O3—C10117.4 (3)O3—C10—H10A109.5
C6—N1—C1117.5 (3)O3—C10—H10B109.5
C7—N3—H3118.7O3—C10—H10C109.5
C7—N3—C8122.7 (3)H10A—C10—H10B109.5
C8—N3—H3118.7H10A—C10—H10C109.5
C13—N4—H4125.6H10B—C10—H10C109.5
C13—N4—C14108.9 (3)C8—C11—H11A108.4
C14—N4—H4125.6C8—C11—H11B108.4
N1—C1—H1118.3H11A—C11—H11B107.4
N1—C1—C2123.4 (4)C12—C11—C8115.6 (3)
C2—C1—H1118.3C12—C11—H11A108.4
C1—C2—H2120.4C12—C11—H11B108.4
C3—C2—C1119.2 (4)C13—C12—C11126.9 (3)
C3—C2—H2120.4C13—C12—C15106.8 (3)
C2—C3—H3A120.5C15—C12—C11126.3 (3)
C2—C3—C4119.0 (4)N4—C13—H13125.1
C4—C3—H3A120.5C12—C13—N4109.9 (3)
C3—C4—C5118.1 (3)C12—C13—H13125.1
C6—C4—C3118.7 (3)N4—C14—C15108.0 (3)
C6—C4—C5123.1 (3)N4—C14—C19130.1 (3)
N2—C5—C4173.8 (4)C19—C14—C15121.8 (3)
N1—C6—C4122.2 (3)C14—C15—C12106.4 (3)
N1—C6—C7116.5 (3)C16—C15—C12134.5 (3)
C4—C6—C7121.3 (3)C16—C15—C14119.0 (3)
O1—C7—N3123.1 (3)C15—C16—H16120.5
O1—C7—C6121.3 (3)C17—C16—C15118.9 (4)
N3—C7—C6115.6 (3)C17—C16—H16120.5
N3—C8—H8107.9C16—C17—H17119.3
N3—C8—C9110.7 (3)C16—C17—C18121.3 (4)
N3—C8—C11111.6 (3)C18—C17—H17119.3
C9—C8—H8107.9C17—C18—H18119.5
C9—C8—C11110.8 (3)C19—C18—C17121.1 (4)
C11—C8—H8107.9C19—C18—H18119.5
O2—C9—O3124.3 (3)C14—C19—H19121.1
O2—C9—C8124.0 (3)C18—C19—C14117.8 (4)
O3—C9—C8111.6 (3)C18—C19—H19121.1
N1—C1—C2—C31.4 (6)C8—C11—C12—C1381.6 (4)
N1—C6—C7—O1171.7 (3)C8—C11—C12—C1599.6 (4)
N1—C6—C7—N38.9 (4)C9—C8—C11—C1250.2 (4)
N3—C8—C9—O213.3 (5)C10—O3—C9—O20.6 (6)
N3—C8—C9—O3169.9 (3)C10—O3—C9—C8176.3 (3)
N3—C8—C11—C1273.6 (4)C11—C8—C9—O2111.1 (4)
N4—C14—C15—C121.3 (3)C11—C8—C9—O365.8 (4)
N4—C14—C15—C16178.0 (3)C11—C12—C13—N4179.2 (3)
N4—C14—C19—C18177.9 (3)C11—C12—C15—C14178.4 (3)
C1—N1—C6—C41.5 (5)C11—C12—C15—C162.4 (6)
C1—N1—C6—C7179.4 (3)C12—C15—C16—C17176.0 (3)
C1—C2—C3—C40.1 (6)C13—N4—C14—C151.4 (4)
C2—C3—C4—C5179.9 (3)C13—N4—C14—C19177.7 (3)
C2—C3—C4—C60.3 (5)C13—C12—C15—C140.7 (3)
C3—C4—C6—N10.4 (5)C13—C12—C15—C16176.6 (4)
C3—C4—C6—C7179.4 (3)C14—N4—C13—C121.0 (4)
C4—C6—C7—O19.2 (5)C14—C15—C16—C170.4 (5)
C4—C6—C7—N3170.1 (3)C15—C12—C13—N40.2 (4)
C5—C4—C6—N1179.2 (3)C15—C14—C19—C181.2 (5)
C5—C4—C6—C70.1 (5)C15—C16—C17—C180.4 (6)
C6—N1—C1—C22.0 (6)C16—C17—C18—C190.5 (6)
C7—N3—C8—C9109.7 (4)C17—C18—C19—C140.3 (5)
C7—N3—C8—C11126.5 (3)C19—C14—C15—C12178.0 (3)
C8—N3—C7—O10.8 (6)C19—C14—C15—C161.2 (5)
C8—N3—C7—C6178.5 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N4—H4···O1i0.862.292.987 (3)138
Symmetry code: (i) x, y, z1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N4—H4···O1i0.862.292.987 (3)137.6
Symmetry code: (i) x, y, z1.
references
References top

Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarton, England.

Devillers, I., Arrault, A., Olive, G. & Marchand-Brynaert, J. (2002). Tetrahedron Lett. 43, 3161–3164.

Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.

Kundu, M., Singh, J., Singh, B., Ghosh, T., Maiti, B. C. & Maity, T. K. (2012). Indian J. Chem. Sect. B, 51, 493–497.

Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.

Peterlin-Mašič, L. & Kikelj, D. (2001). Tetrahedron, 57, 7073–7105.

Sakamoto, T., Cullen, M. D., Hartman, T. L., Watson, K. M., Buckheit, R. W., Pannecouque, C., DeClercq, E. & Cushman, M. (2007). J. Med. Chem. 50, 3314–3319.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Tyrkov, A. G. & Sukhenko, L. T. (2004). Pharm. Chem. J. 38, 30–38.