Ethyl 7-(4-bromophenyl)-5-trifluoromethyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate

In the title compound, C14H11BrF3N5O2, the pyrimidine ring adopts a flattened envelope conformation with sp 3-hybridized carbon as the flap [deviation = 0.177 (3) Å]. The dihedral angle between tetrazole and bromophenyl rings is 84.3 (1)°. In the crystal, molecules are linked into centrosymmetric dimers by pairs of N—H⋯N hydrogen bonds.


Comment
The tetrazolo[1,5-a]pyrimidine core represents an interesting pharmacophore with the feature of biological and pharmacological properties, which has human neutrophil elastase inhibitory (Von Nussbaum et al., 2010), late sodium channel blocker (Abelman et al., 2009) and hepatitis B virus surface antigen secretion inhibitory activities (Dougherty et al., 2007). This led us to pay much attention to the synthesis and bioactivity of compounds containing these two significant fragments. During the synthesis of trifluoromethylated tetrazolo[1,5-a]pyrimidine derivatives, the title compound was isolated and its structure was determined by X-ray analysis. The results are presented here.
The crystal packing is stabilized by intermolecular N-H···N hydrogen bonds (Table 1 and Fig.2).

Experimental
The title compound was synthesized according the procedure reported by Pryadeina et al.(2004). A mixture of ethyl 4,4,4trifluoro-3-oxobutanoate (0.01 mol), 4-bromobenzaldehyde (0.01 mol) and 5-aminotetrazole (0.01 mol) in ethanol (20 ml) containing a catalytic amount of hydrochloric acid was heated for 12 h under reflux. Then the solvent was removed under reduced pressure. The residue was added to a solution of p-toluenesulfonic acid (0.05 g) in 100 mL of benzene, and the mixture was heated for 8 h with simultaneous removal of water as azeotrope with benzene. The solution was filtered while hot, the filtrate was evaporated, and the precipitate was recrystallized from ethanol. Cooling the ethanol solution slowly gave single crystals suitable for X-ray diffraction.

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.