INDUSTRIAL PROCESS FOR THE PREPARATION OF HEXANOIC ACID, 6(NITROOXY)-,(1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ETHYLAMINO)-7-OXO-2-HEPTEN-1-YL]3,5-DIHYDROXYCYCLOPENTYL]-1-(2-PHENYL ETHYL)-2-PROPEN-1-YL ESTER AND HIGH PURE PRODUCT

• Main Authors: Kovács, Szabolcs, Sántáné Csutor, Andrea, Hortobágyi, Irén, Póti, Judit, Ronsin, Gael, Almirante, Nicoletta
• Format: Patent
• Language: English; French; German
• Published: 10.01.2024
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl esterIn accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6-(nitrooxy)hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step.The invention refers also to high purity Compound (I) substantially free of the impurity 15-(6-chlorohexanoyl) ester of bimatoprost and to ophthalmic pharmaceutical formulations containing the high purity compound.