Crystal structure of 2-acetyl-5-(3-methoxyphenyl)-3,7-dimethyl-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate

In the title molecule, C20H22N2O4S, the pyrimidine ring is in a flattened half-chair conformation and the 3-methoxyphenyl substituent is in an axial arrangement. The thiazole ring forms a dihedral angle of 81.3 (1)° with the benzene ring. In the crystal, weak C—H⋯S interactions link molecules into chains along [001]. In addition, there are π–π interactions between inversion-related thiazole rings with a centroid–centroid distance of 3.529 (2) Å. The ethyl group was refined as disordered over two sets of sites with an occupancy ratio of 0.52 (3):0.48 (2).

For pharmacological and biological properties of pyrimidine derivatives, see: Alam et al. (2010a,b). For the therapeutic potential of thiazolopyrimidine derivatives, see: Zhi et al.   Table 1 Hydrogen-bond geometry (Å , ). group adopts a syn periplanar conformation with respect to the C5-H5 bond of the pyrimidine ring. The pyrimidine ring is in a flattened half chair conformation with atoms N1 and C5 displaced by -0.082 (3) and 0.189 (4)Å, respectively from the mean plane of the other four atoms (N2/C6/C7/C9). The 3-methoxy phenyl substituent bonded to atom C5 is in an axial position. The ethyl group was refined as disordered over two sets of sites with an occupancy ratio of 0.52 (3):0.48 (2). The bond lengths and angles in the title compound are in good agreement with the corresponding bond distances and angles reported in closely related structures (Nagarajaiah et al., 2012;Jotani et al., 2010). In the crystal, weak C-H···S interactions link molecules into chains along [001] (Fig. 2). In addition, there are π···π interactions between inversion related thiazole rings with a centroid-centroid distance of 3.529 (2) Å.

S2. Experimental
A mixture of 4-(3-methoxy-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (10 mmol) and 3-chloro-2,4-pentanedione (10 mmol) was refluxed in dry ethanol (20 mmol) for 12 h. The excess of solvent was distilled off and the solid hydrochloride salt that separated was collected by filtration, suspended in water and neutralized by aqueous sodium carbonate solution to yield the free base. The solution was filtered, the solid washed with water, dried and recrystallized from ethyl acetate to give the title compound (76% yield, mp 380 K). The compound was recrystallized by slow evaporation from 1:1 mixture of ethyl acetate and methanol , yielding pale-yellow single crystals suitable for X-ray diffraction studies.

S3. Refinement
The H atoms were placed at calculated positions in the riding-model approximation with C-H = 0.95° A, 1.00 Å and 0.96 Å for aromatic, methyne and methyl H-atoms respectively, with U iso (H) = 1.5U eq (C) for methyl H atoms and U iso (H) = 1.2U eq (C) for other hydrogen atoms.
supporting information

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius. The primed atoms indicate the disorder.   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.34 e Å −3 Δρ min = −0.39 e Å −3 Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s 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 > 2σ(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.