Raltegravir monohydrate

Abstract

The hydrated title compound [systematic name: N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-{1-methyl-1-[(5-methyl-1,3,4-oxadiazol-2-ylcarbonyl)amino]ethyl}-6-oxo-1,6-dihydropyrimidine-4-carboxamide monohydrate], C20H21FN6O5·H2O, is recognised as the first HIV integrase inhibitor. In the molecule, the dihedral angles between the mean planes of the pyrimidine ring and the phenyl and oxadiazole rings are 72.0 (1) and 61.8 (3)°, respectively. The mean plane of the oxadiazole ring is twisted by 15.6 (3)° from that of the benzene ring, while the mean plane of amide group bound to the oxadiaole ring is twisted by 18.8 (3)° from its mean plane. Intramolecular O—H...O and C—H...N hydrogen bonds are observed in the molecule. The crystal packing features O—H...O hydrogen bonds, which include bifurcated O—H...(O,O) hydrogen bonds from one H atom of the water molecule. In addition, N—H...O hydrogen bonds are observed involving the two amide groups. These interactions link the molecules into chains along [010]

Structural analysis of anti-retroviral drug raltegravir and its potential impurity C: investigation of solubility and stability

“…The XRD pattern of the RLT hydrate and RLT-K salt are reported in the literature. 11,12 The characteristic diffraction peaks at 2 θ 12.3, 13.2, 19.6, 20.2, 22.4, 23.3, 24.6, 25.3 and 27.5 ± 0.2° confirmed the presence of the RLT K salt. The diffraction peaks at 8.0, 11.2, 13.5, 15.0, 15.9, 22.5, 25.1, 27.3 and 29.9 ± 0.2° 2 θ correspond to the RLT monohydrate.…”

“…PXRD of the white residue confirmed as reported RLT hydrate phase. 12 Common reagents like conc. HCl, acetone, methanol, ethanol, isopropanol, ethyl acetate, acetonitrile, THF, DMF, DMSO and pH 6.8 buffer capsules were procured from Siscon Research Laboratories, Chennai and utilised to prepare various solid forms.…”

“…A fixed dose combined therapy of RLT with lamivudine was also approved in 2015 and commercialized under the brand name Dutrebis. Although the crystal structure of the RLT-K salt and monohydrate is reported in the literature, 11,12 the structures of RLT polymorphs with improved chemical stability are yet to be published. According to patent WO 2011/024192A2, there are three free hydroxy forms reported, but their crystal structures (3D coordinates) are unknown to date.…”