METODOS PARA SINTETIZAR UN ANALOGO DE LA PROSTACICLINA

• Main Authors: MAHMOUD, HUSSEIN MAHMOUD, ENDRES, GREGORY WILLIAM, FEDIJ, VICTOR, HERING, KIRK WILLIAM, KRELL II, THOMAS JAMES, CHAMBOURNIER, GILLES
• Format: Patent
• Language: Spanish
• Published: 20.02.2016
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

Un metodo para generar un compuesto treprostinil de Formula I o una de sus sales farmaceuticamente aceptables, que comprende los siguientes pasos: i) hacer reaccionar un compuesto de Formula 9 con un agente oxidante en presencia de un disolvente organico para generar un compuesto de Formula 10 donde R1 es alquilo C1-6 y el agente oxidante comprende MnO2 o peryodinano de Dess-Martin; ii) hacer reaccionar el compuesto de Formula 10 con un compuesto de Formula 5 en presencia de una base y un disolvente organico para generar un compuesto de Formula 11, donde cada R2 se selecciona independientemente entre alquilo C1-6 o fenilo; y iii) convertir el compuesto de Formula 11 en el compuesto treprostinil de Formula I The present invention provides processes for preparing a prostacyclin analogue of Formula I or a pharmaceutically acceptable salt thereof, wherein R 10 is a linear or branched C 1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.