Asymmetric catalytic reduction of oxcarbazepine

• US 9,643,929 B2
• Filed: 11/18/2015
• Issued: 05/09/2017
• Est. Priority Date: 07/29/2005
• Status: Active Grant

• Current Assignee: BIAL Portela & Ca, SA
• Original Assignee: BIAL Portela & Ca, SA
• Inventors: Learmonth, David Alexander, Grasa, Gabriela Alexandra, Zanotti-Gerosa, Antonio
• Primary Examiner(s): COLEMAN, BRENDA LIBBY
• Application Number:
  US14/944,546
• Publication Number:
  US 20160176823A1
• Time in Patent Office: 538 Days
• Field of Search: 514217, 540589
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 31/08 for leprosy
• CPC Class Codes: C07D 223/22 Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
• CPC Class Codes: C07D 223/28 having a single bond between positions 10 and 11

Abstract

A process for preparing (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide or (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide, by reduction of oxcarbazepine in the presence of a catalyst and a hydride source is disclosed. The catalyst is prepared from a combination of [RuX₂(L)]₂ wherein X is chlorine, bromine or iodine, and L is an aryl or aryl-aliphatic ligand, with a ligand of formula (A) or formula (B):

wherein R¹ is chosen from C_1-6 alkoxy and C_1-6 alkyl, n is a number from 0 to 5, and when n is a number from 2 to 5, R¹ can be the same or different, and R² is alkyl, substituted alkyl, aryl, substituted aryl, alkaryl or substituted alkaryl. The hydride source is either NR³R⁴R⁵ and formic acid, [R³R⁴R⁵NH][OOCH] and optionally formic acid, or [M][OOCH]_x and formic acid, wherein R³, R⁴ and R⁵ are C_1-6 alkyl, M is an alkali metal or alkaline earth metal and x is 1 or 2. A pH from 6.5 to 8 is maintained during the process.

Claims

1. A pharmaceutical composition comprising (S)-(−

)-10-acetoxy-10, 11-dihydro-5H-dibenz/b,f/azepin-5-carboxamide having a chemical purity of at least about 99.96%.

2. A pharmaceutical composition comprising an active pharmaceutical ingredient consisting of (S)-(−

)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepin-5-carboxamide having a chemical purity of at least about 99.96%.

3. The composition of claim 2, wherein the amount of (R)-isomer of (S)-(−

)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepin-5-carboxamide is below the limit of detection.