DNT-fumarate and methods of preparation thereof
OwnerSantiago Ini, Anita Liberman +2inventors
InventorsSantiago Ini, Anita Liberman, Mili Abramov, Tamas Koltai
Life of this patent
Estimating the term…
Abstract
(S)-N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine fumarate (DNT-fumarate) and polymorphs of DNT-fumarate, compositions of DNT-fumarate and its polymorphs, processes for the preparation of DNT-fumarate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-fumarate are provided.
Claims36
A compound (DNT-fumarate) having the following formula:
A process for preparing duloxetine hydrochloride comprising preparing a solution of DNT in a solvent selected from the group consisting of C1-8 alcohols, C3-7 esters, C3-8 ethers, C3-7 ketones, C6-12 aromatic hydrocarbons, acetonitrile, water, and mixtures thereof, combining the solution with fumaric acid to form a reaction mixture, precipitating DNT-fumarate from the reaction mixture, and converting the crystalline DNT-fumarate to the duloxetine hydrochloride.
A crystalline form of DNT-fumarate:
- characterized by a powder XRD with peaks at about 9.7°, 16.5°, 17.4°, 21.2°, and 24.1°2θ±0.2°2θ.
A process for preparing a pharmaceutically acceptable salt of duloxetine, comprising combining DNT, a solvent selected from the group consisting of C1-8 alcohols, C3-7 esters, C3-8 ethers, C3-7 ketones, C6-12 aromatic hydrocarbons, acetonitrile, water and mixtures thereof with fumaric acid to form a reaction mixture, precipitating DNT-fumarate from the reaction mixture, converting the DNT-fumarate to DNT, converting the DNT to duloxetine, and converting the duloxetine to the pharmaceutically acceptable salt of duloxetine.
Dependencies are inferred from the claim text.