Crystal structure and Hirshfeld surface analysis of ethyl (3E)-5-(4-fluorophenyl)3-{[(4-methoxyphenyl)formamido]imino}-7-methyl-2H,3H,5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate 0.25-hydrate

The dihydropyrimidine ring in the title molecule is distinctly non-planar. In the crystal, zigzag chains parallel to [010] are formed by N—H⋯N hydrogen bonds and are connected into layers parallel to (100) by O—H⋯O, O—H⋯F, C—H⋯O, C—H⋯F and C—H⋯N hydrogen bonds. Further C—H⋯O hydrogen bonds connect the layers.


Chemical context
Interest in the anticancer activities of dihydropyrimidines (DHPMs) has been increasing since 1999, when monastrol was discovered (Mayer et al., 1999;Leizerman et al., 2004). In addition, 1,3,4-oxadiazole has been reported to exhibit a significant anticancer activity (Yadagiri et al., 2015;Valente et al., 2014;El-Din et al., 2015). Since the combination of two or more pharmacophoric structural moieties can possibly augment the bioactivity, it was of interest to hybridize the DHPM moiety with 1,3,4-oxadiazole, hoping to discover potent anticancer agents.

Figure 3
View of the molecular packing along [010]. Hydrogen bonds are depicted as in Fig. 2.

Figure 1
The title molecule with the labelling scheme and displacement ellipsoids drawn at the 30% probability level.

Table 2
Summary of short interatomic contacts (Å ) in the title compound.. Asterisks relate to atoms of the underoccupied water molecule.
In (III), pairs of weak C-HÁ Á ÁO hydrogen bonds lead to the formation of inversion dimers. A weak C-HÁ Á Á interaction andstacking interactions are observed.
The crystal packing of (VI) is influenced by weak intermolecular C-HÁ Á Á interactions andstacking between the thiazole and phenyl rings, which stack the molecules parallel to [001].
In (VIII), short intermolecular C-HÁ Á ÁO, C-HÁ Á Á and stacking interactions contribute to the stability of the crystal packing. In (IX), molecules are linked into a three-dimensional network by intermolecular C-HÁ Á ÁO and C-HÁ Á ÁF hydrogen bonds. The crystal structure is further stabilized by a C-HÁ Á Á interaction.
Compounds (X) and (XI) crystallize in two polymorphic forms having the same space-group type, viz. P1, with Z 0 = 2 and Z 0 = 1. In both polymorphs, the molecules are linked by N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The H atoms were found in difference-Fourier maps; all C and N-bound H atoms were refined freely. The water molecule was found to be occupationally disordered and was refined with a fixed site occupa-  tion factor of 1/4. The H atoms of the water molecules were located in a difference-Fourier map, their bond lengths set to an ideal value of 0.87 Å , and were refined with U iso (H) = 1.5 U eq (O) using a riding model.

sup-1
Acta Cryst. publCIF (Westrip, 2010). Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness 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 threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) 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. Refinement of the site occupancy factor for the lattice water (O5) converged at ca. 0.25. This was fixed at this value for the remainder of the refinement, the attached hydrogen atoms were located in a difference map and included as riding contributions in idealized positions.