Synthesis and comprehensive structural and physicochemical characterization of dutasteride hydrochloride hydrate solvates

Abstract

Four crystalline dutasteride hydrochloride hydrate solvates containing respectively methanol, ethanol, acetone and acetonitrile molecules were obtained. All samples were characterized by extensive spectroscopic analysis with infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and ¹H as well as ¹³C NMR techniques. For three solvates, i.e. methanol, ethanol and acetone solvates, the single crystal X-ray diffraction (SCXRD) experiments were possible, and their respective crystal and molecular structures were determined. The present study allowed to unambiguously establish the molecular composition of solvates as consisting of a dutasteride : hydrogen chloride : water : solvent in a molar ratio of 1:1:1:1 and confirm that they are isostructural. Beyond providing the full spectroscopic characteristic of the compounds, the results obtained have also allowed clarifying of some appearing inconsistencies in published literature regarding the appropriate attribution of IR absorption bands to the relevant molecular vibrations.

Keywords: 3-Oxo-4-aza-5α-androstane-17β-carboxylic acid (PubChem CID: 9818495).; Differential scanning calorimetry; Dihydrodutasteride, i.e. N-tert-butyl-3-oxo-4-aza-5α-androstane-17β-carboxamide, (PubChem CID: 58077530);; Dihydrofinasteride, i.e. N-tert-butyl-3-oxo-4-aza-5α-androstane-17β-carboxamide, (PubChem CID: 9864387);; Dutasteride; Dutasteride hydrochloride hydrate solvates; Dutasteride, i.e. N-[2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, (PubChem CID: 6918296);; Finasteride, i.e. N-tert-butyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, (PubChem CID: 57363);; IR spectroscopy; NMR spectroscopy; Single crystal X-ray analysis.