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

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).

The title compound, C 13 H 16 N 4 O 3 S 2 ÁH 2 O, 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-HÁ Á ÁO hydrogen bond, and an N-HÁ Á ÁO hydrogen-bonding interaction involving the lattice water molecule. The packing involves N-HÁ Á ÁN, N-HÁ Á ÁO, O-HÁ Á ÁN and O-HÁ Á ÁO 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).

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). Aminocyanopyridines 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.

Refinement
H-atoms attached to carbon were placed in calculated positions (C-H = 0.95 -0.98 Å) while those attached to nitrogen were placed in locations derived from a difference map and their coordinates adjusted to give N-H = 0.91 Å. All were included as riding contributions with isotropic displacement parameters 1.2 -1.5 times those of the attached atoms.

Figure 1
Perspective view of the asymmetric unit with 50% probability ellipsoids and hydrogen bonds depicted by dashed lines.  Packing projected along the c axis showing the tilted layers.

Figure 4
Packing viewed along the axis of the channels. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level. Special details Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles Refinement. Refinement on F 2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The observed criterion of F 2 > σ(F 2 ) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.