Methyl 2-{6-[(1-meth­oxy-1-oxopropan-2-yl)amino­carbon­yl]pyridine-2-carboxamido}­propano­ate

Mohamed A Al-Omar; Abdel-Galil E Amr; Hazem A Ghabbour; Tze Shyang Chia; Hoong-Kun Fun

doi:10.1107/S1600536812022258

. 2012 May 23;68(Pt 6):o1837–o1838. doi: 10.1107/S1600536812022258

Methyl 2-{6-[(1-methoxy-1-oxopropan-2-yl)aminocarbonyl]pyridine-2-carboxamido}propanoate

Mohamed A Al-Omar ^a,^b, Abdel-Galil E Amr ^b,^c, Hazem A Ghabbour ^a, Tze Shyang Chia ^d, Hoong-Kun Fun ^d,^*,^‡

PMCID: PMC3379408 PMID: 22719606

Abstract

In the title compound, C₁₅H₁₉N₃O₆, the amide planes are inclined at dihedral angles of 0.8 (6) and 12.1 (3)° with respect to the central pyridine ring. The mean planes of the corresponding methyl acetate groups form dihedral angles of 41.76 (13) and 86.48 (15)°, respectively with the mean plane of pyridine ring. A pair of weak intramolecular N—H⋯N hydrogen bonds generate an S(5)S(5) ring motif in the molecule. In the crystal, molecules are linked by N—H⋯O hydrogen bonds into [001] chains. The chains are cross-linked by C—H⋯O hydrogen bonds into layers lying parallel to bc plane. The crystal packing also features a C—H⋯π interaction.

Related literature

For the synthesis and biological activity screening of some dipicolinic acid bis-l-amino acid hydrazide derivatives and their corresponding acids, see: Abou-Ghalia & Amr (2004 ▶); Al-Salahi et al. (2010 ▶); Al-Omar & Amr (2010 ▶); Attia et al. (2000 ▶). For the biological activity of 2,6-disubstituted pyridine derivatives, see: Amr (2005 ▶); Abou-Ghalia et al. (2003 ▶); Amr, Sayed & Abdulla (2005 ▶); Amr et al. (2006 ▶); Hammam et al. (2003 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). graphic file with name e-68-o1837-scheme1.jpg

Experimental

Crystal data

C₁₅H₁₉N₃O₆
M _r = 337.33
Monoclinic,
a = 8.9735 (3) Å
b = 20.7073 (8) Å
c = 10.4048 (5) Å
β = 122.901 (3)°
V = 1623.29 (11) Å³
Z = 4
Cu Kα radiation
μ = 0.91 mm⁻¹
T = 296 K
0.74 × 0.25 × 0.06 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.551, T _max = 0.947
10358 measured reflections
2703 independent reflections
2058 reflections with I > 2σ(I)
R _int = 0.046

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.192
S = 1.04
2703 reflections
229 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812022258/hb6780sup1.cif

e-68-o1837-sup1.cif^{(26.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812022258/hb6780Isup2.hkl

e-68-o1837-Isup2.hkl^{(132.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812022258/hb6780Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the N1/C1–C5 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H1N3⋯N1	0.85 (3)	2.23 (3)	2.676 (3)	113 (2)
N3—H1N3⋯O4ⁱ	0.85 (2)	2.35 (2)	3.080 (2)	145 (2)
N2—H1N2⋯N1	0.84 (3)	2.32 (3)	2.685 (3)	107 (3)
N2—H1N2⋯O4ⁱ	0.83 (3)	2.55 (3)	3.290 (3)	149 (2)
C9—H9B⋯O2ⁱⁱ	0.96	2.41	3.329 (3)	159
C15—H15B⋯Cg1ⁱⁱⁱ	0.96	2.78	3.544 (4)	137

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

MAO, AEA and HAG thank the Deanship of Scientific Research at King Saud University for funding through the research group project No. RGP-VPP-099. HKF and TSC thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). TSC also thanks the Malaysian Government and USM for the award of a research fellowship.

supplementary crystallographic information

Comment

In our previous work (Abou-Ghalia & Amr, 2004; Al-Salahi et al., 2010; Al-Omar & Amr, 2010), we have reported the synthesis and biological activity screening of some dipicolinic acid bis-L-amino acid hydrazide derivatives and their corresponding acids (Attia et al., 2000). In view of the significance of 2,6-disubstituted pyridine derivatives as biologically active congeners (Amr, 2005; Abou-Ghalia, Amr & Abdulla, 2003; Amr, Sayed & Abdulla, 2005; Amr et al., 2006; Hammam et al., 2003), we report herein the synthesis and crystal structure of the title compound.

The asymmetric unit of the title compound is shown in Fig. 1. The amide planes (O1/N2/C6 & O4/N3/C11) are inclined at dihedral angles of 0.8 (6) and 12.1 (3)°, respectively, with respect to the central pyridine ring (N1/C1–C5). The mean planes of the methyl acetate groups (O2/O3/C7–C9 with maximum deviation = 0.007 (2) Å at atom O3 & O5/O6/C12–C14 with maximum deviation = 0.011 (2) Å at atom O6) form dihedral angles of 41.76 (13) and 86.48 (15)°, respectively with the mean plane of pyridine ring. Weak intramolecular N2—H1N2···N1 and N3—H1N3···N1 hydrogen bonds (Table 1) generate an S(5)S(5) ring motif (Bernstein et al., 1995) in the molecule.

In the crystal (Fig. 2), molecules are linked by intermolecular N3—H1N3···O4, N2—H1N2···O4 and C9—H9B···O2 hydrogen bonds (Table 1) into two-dimensional networks parallel to bc plane. The crystal packing is further stabilized by C—H···π interaction (Table 1), involving Cg1 which is the centroid of N1/C1–C5 ring.

Experimental

To a cold mixture (-15 °C) of 2,6-pyridine dicarboxylic acid (0.167 g, 1 mmol) in cold dry tetrahydrofuran (100 ml) and ethyl chloroformate (0.216 g, 2 mmol), triethylamine (0.202 g, 2 mmol) was added with stirring. After 10 min, D-alanyl methyl ester (0.206 g, 2 mmol) was then added. The reaction mixture was stirred for 3 h at -15 °C and then 12 h at r.t. The triethylamine hydrochloride formed was filtered off and the solvent was evaporated under reduced pressure. The residue obtained was dissolved in 150 ml dichloromethane, washed with water, 1 N hydrochloric acid, 1 N sodium bicarbonate and finally with water and dried over anhydrous calcium chloride. The solvent was evaporated under reduced pressure to dryness and the obtained solid was crystallized from dichloromethane to give colourless plates of the title compound.