Methyl 5′-(2-hydroxyphenyl)-4′,5′,6′,7′-tetrahydrospiro[2H-1-benzopyran-2,7′-1,2,4-triazolo[1,5-a]pyrimidine]-3-carboxylate

There are two crystallographically independent molecules in the asymmetric unit of the title compound, C21H18N4O4. The substituted benzopyran portion of one of the independent molecules exhibits disorder [occupancy 0.5248 (18):0.4752 (18)], which was modelled by using two sets of atomic positions and restraints on the chemically equivalent bond lengths and angles. The central, partially saturated pyrimidine rings of both independent molecules were found to assume unsymmetrical half-chair conformations. The hydroxyphenyl substituent occupies an equatorial position in both molecules, and is rotated by 55.6 (1)° from the mean plane of the pyrimidine ring in one independent molecule, and by 53.4 (1)° in the other. In the crystal, there are two types of intermolecular hydrogen bond present: reciprocal N—H⋯N interactions join the two crystallographically independent molecules into a dimer and O—H⋯N interactions link the dimers into sheets in the ab plane.

There are two crystallographically independent molecules in the asymmetric unit of the title compound, C 21 H 18 N 4 O 4 . The substituted benzopyran portion of one of the independent molecules exhibits disorder [occupancy 0.5248 (18): 0.4752 (18)], which was modelled by using two sets of atomic positions and restraints on the chemically equivalent bond lengths and angles. The central, partially saturated pyrimidine rings of both independent molecules were found to assume unsymmetrical half-chair conformations. The hydroxyphenyl substituent occupies an equatorial position in both molecules, and is rotated by 55.6 (1) from the mean plane of the pyrimidine ring in one independent molecule, and by 53.4 (1) in the other. In the crystal, there are two types of intermolecular hydrogen bond present: reciprocal N-HÁ Á ÁN interactions join the two crystallographically independent molecules into a dimer and O-HÁ Á ÁN interactions link the dimers into sheets in the ab plane.
by using a single-crystal X-ray analysis. Another aim of this work was to obtain complete structural data indispensable for studying structure-activity relationships.
The structure determination ( Fig.1) confirmed the spectroscopic assignments, i.e. (I) is indeed the correct structure of the compound. The asymmetric unit of the structure comprises two molecules (A and B) of (I). Moreover, the methoxycarbonylbenzopyran moiety of molecule B is disordered between two well defined positions (denoted by unprimed and primed atomic symbols) with approximately equal occupancies. The disordered sites differ in (i) ca 20°-rotation of the substituted benzopyran ring about an axis passing through the spiro (C26) atom and perpendicular to the mean plane of the ring and (ii) the conformation of the ester group.
As mentioned above, from the pharmacological viewpoint the most important aspect of the molecular structure ( Fig.1) concerns three-dimensional disposition of the key functional (pharmacophoric) elements (hydrophobic groups and heteroatoms able to form hydrogen bonds) which can be expressed in terms of the conformationl parameters of the molecule.
Thus, the conformation of the central pyrimidine ring in both molecules can best be described as an unsymmetrical half-chair.
The hydroxyphenyl ring occupies an equatorial position on C3 and is inclined at an angle of 55.6 (1)° to the mean plane of the heterocycle. The corresponding dihedral angle in molecule B is 53.4 (1)°. As to the conformation of the ester group, its carbonyl bond is oriented anti (with respect to the neighbouring double bond of the benzopyran moiety) in molecule A and the unprimed sites of molecule B while the orientation is syn for the primed isomer.
In the crystal, there are two types of intermolecular hydrogen bond present: reciprocal N-H···N interactions join the two crystallographically independent molecules into a dimer ( Figure 1) and an O-H···N interaction links the dimers into a two-dimensional sheet in the ab plane.