Ethyl 2-[({[4-amino-5-cyano-6-(methyl­sulfan­yl)pyridin-2-yl]carbamo­yl}meth­yl)sulfan­yl]acetate monohydrate

Mehmet Akkurt; Joel T Mague; Shaaban K Mohamed; Bahgat R M Hussein; Mustafa R Albayati

doi:10.1107/S1600536814012495

. 2014 Jun 4;70(Pt 7):o745–o746. doi: 10.1107/S1600536814012495

Ethyl 2-[({[4-amino-5-cyano-6-(methylsulfanyl)pyridin-2-yl]carbamoyl}methyl)sulfanyl]acetate monohydrate

Mehmet Akkurt ^a, Joel T Mague ^b, Shaaban K Mohamed ^c,^d, Bahgat R M Hussein ^e, Mustafa R Albayati ^f,^*

PMCID: PMC4120541 PMID: 25161542

Abstract

The title compound, C₁₃H₁₆N₄O₃S₂·H₂O, crystallizes in a ‘folded’ conformation with the ester group lying over the carbamoyl moiety, with one solvent water molecule. The molecular conformation is stabilized by an intramolecular C—H⋯O hydrogen bond, and an N—H⋯O hydrogen-bonding interaction involving the lattice water molecule. The packing involves N—H⋯N, N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds and consists of tilted layers running approximately parallel to the c axis, with the ester groups on the outer sides of the layers and with channels running parallel to (101).

Related literature

For the synthesis of amino-cyano pyridines, see: Shi et al. (2005 ▶). For pyridines as intermediates in the synthesis of different heterocyclic compounds, see: Konda et al. (2010 ▶). For the pharmaceutical activity of functionalized pyridine derivatives, see: Dorigo et al. (1993 ▶); Dolle et al. (1995 ▶); Murata et al. (2003 ▶). For industrial applications of pyridine compounds, see: Lohray et al. (2004 ▶); Merja et al. (2004 ▶); Chaki et al. (1995 ▶); Thomae et al. (2007 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). graphic file with name e-70-0o745-scheme1.jpg

Experimental

Crystal data

C₁₃H₁₆N₄O₃S₂·H₂O
M _r = 358.45
Triclinic,
a = 9.0806 (12) Å
b = 9.2444 (12) Å
c = 10.7856 (14) Å
α = 101.843 (2)°
β = 100.1750 (19)°
γ = 105.9480 (19)°
V = 825.48 (19) Å³
Z = 2
Mo Kα radiation
μ = 0.35 mm⁻¹
T = 150 K
0.26 × 0.26 × 0.12 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2013 ▶) T _min = 0.83, T _max = 0.96
15313 measured reflections
4292 independent reflections
3773 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.099
S = 1.05
4292 reflections
210 parameters
H-atom parameters constrained
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.37 e Å⁻³

Data collection: APEX2 (Bruker, 2013 ▶); cell refinement: SAINT (Bruker, 2013 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXT (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg & Putz, 2012 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814012495/sj5406sup1.cif

e-70-0o745-sup1.cif^{(24.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814012495/sj5406Isup2.hkl

e-70-0o745-Isup2.hkl^{(235.4KB, hkl)}

Click here for additional data file.^{(6.3KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814012495/sj5406Isup3.cml

CCDC reference: 1005734

Additional supporting information: crystallographic information; 3D view; checkCIF report

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3A⋯N2ⁱ	0.91	2.43	3.3291 (18)	168
N3—H3B⋯O1ⁱⁱ	0.91	2.03	2.9345 (18)	177
N4—H4A⋯O4	0.91	2.01	2.9212 (16)	174
O4—H4B⋯N2ⁱⁱⁱ	0.84	2.17	3.0032 (19)	172
O4—H4C⋯O2^iv	0.84	2.09	2.9122 (18)	168
C4—H4⋯O1	0.95	2.25	2.8484 (17)	121

Open in a new tab

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

Acknowledgments

JTM thanks Tulane University for support of the Tulane Crystallography Laboratory.

supplementary crystallographic information

S1. Comment

A great deal of interest has been focused on the synthesis of functionalized pyridine derivatives due to their biological activities (Shi et al., 2005). For example, some 2-pyridine radicals are incorporated into the structures of cardiotonic agents such as milrinone (Dorigo et al., 1993) and HIV-1 specific transcriptase inhibitors (Dolle et al., 1995). Amino-cyanopyridines have been identified as IKK-β inhibitors (Murata et al., 2003). Many pyridine derivatives are of commercial interest being used as herbicides, fungicides, pesticides, and dyes (Lohray et al., 2004; Merja et al., 2004; Chaki et al., 1995; Thomae et al., 2007). Besides, pyridine derivatives are important and useful intermediates in the preparation of a variety of heterocyclic compounds (Konda et al., 2010). In view of these observations and in continuation of our work on the synthesis of heterocyclic systems for biological evaluations, we report here the synthesis and crystal structure of the title compound.

The title compound (Fig. 1) crystallizes in a "folded" conformation with the ester group lying over the carbamoyl moiety such that the dihedral angle between the best planes through the pyridyl ring and the C11–C13/O3 unit is 22.4 (1)°.

Molecular conformation is stabilized by an intramolecular C—H···O hydrogen bond, forming a S(6) motif, Fig. 1, (Bernstein et al., 1995) and an N—H···O hydrogen bonding interaction involving the lattice water molecule.

This conformation appears to result from the several hydrogen bonding interactions involving the lattice water molecule, Fig. 2 and Table 1. The packing consists of tilted layers running approximately parallel to the c axis, Fig. 3, with the ester groups on the outsides of the layers and having channels running parallel to (101), Fig. 4.

S2. Experimental

To a solution of N-[4-amino-5-cyano-6-(methylthio)pyridin-2-yl]-2-chloroacetamide (0.5 g, 1.95 mmol) in 30 ml ethanol and a few drops of triethylamine as a catalyst, ethyl mercaptoacetate (0.23 g, 1.95 mmol) was added. The reaction mixture was refluxed for 3 h at 350 K. The reaction mixture was allowed to cool down and the excess solvent was evaporated under reduced pressure. The precipitate which formed was filtered off, dried under vacuum and recrystallized from ethanol to furnish colourless crystals (yield 0.62 g; 95%). Mp. 423 – 425 K.

IR (ν_max, cm^-1): 3431, 3335, 3227, (NH₂+NH), 2915 (CH aliph.), 2203 (C≡N), 1728 (C=O ester), 1641 (C=O amidic); ¹HNMR (DMSO-d₆), δ, p.p.m.: 10.34 (s, 1H, NH exchanged by D₂O), 7.28 (s, 1H, CH pyridyl), 7.00 (s, 2H, NH₂ exchanged by D₂O), 4.11- 4.06(q, J = 8 Hz, 2H, CH₂), 3.50 (s, 2H, CH₂), 3.49 (s, 2H, CH₂), 2.53 (s, 3H, CH₃), 1.2–1.17 (t, J = 8 Hz, 3H, CH₃).