Antitumour imidazotetrazines. Part 5. Crystal and molecular structure of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3h)-one (mitozolomide)

Abstract

The structure of the novel bicyclic antitumour agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (Mitozolomide) has been investigated by single-crystal X-ray diffraction methods. The compound crystallizes in the triclinic space group P in a cell of dimensions a= 7.003(4), b= 8.680(4), c= 16.041(9)Å, α= 93.76(5), β= 93.99(5), γ= 92.08(7)° with Z= 4. The structure was solved by direct methods and refined using full-matrix least-squares calculations, which at convergence produced a final R index of 0.052 for the 3 244 observed data. The two independent molecules per asymmetric unit are rotamers about the C(8)–C(81) and C(8)′–C(81)′ bonds, the orientation of the carbamoyl group in one rotamer facilitating an intramolecular hydrogen bond of the type N–H ⋯ N. With the exception of the chloroethyl side chain, both molecules are approximately planar and intermolecular hydrogen bonds hold groups of four molecules together around the centre of symmetry.