Method for producing lacosamide and intermediate thereof

Patent metadata

Field	Value
Publication number	US-2018371013-A1
Application number	US-201615775581-A
Country	US
Kind code	A1
Filing date	Nov 11, 2016
Priority date	Nov 13, 2015
Publication date	Dec 27, 2018
Grant date	—

Abstract

The present invention provides a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Adopting a particular isomerization-crystallization condition makes it possible to a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Additionally, an intermediate efficacious for producing lacosamide is provided.

First claim

1 . A method for producing lacosamide comprising:
an isomerization-crystallization process that causes racemic N-benzyl-2-amino-3-methoxypropionamide to react with at least one selected from a group consisting of N-acetylamino acid and N-formylamino acid in a solvent in the presence of an aldehyde compound at a temperature lower than 65° C. to selectively crystallize a salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid or N-formylamino acid; and an acetylation process that acetylates the R-configuration N-benzyl-2-amino-3-methoxypropionamide contained in the salt to obtain lacosamide.

2 . The method according to claim 1 , wherein an amount of the solvent is 20 mL or less to the racemic N-benzyl-2-amino-3-methoxypropionamide of one gram.

3 . The method according to claim 1 , wherein, in the isomerization-crystallization process, at least one selected from a group consisting of the N-acetylamino acid and the N-formylamino acid is dividedly provided.

4 . The method according to claim 1 , wherein the acetylation process comprises:
(i) causing the salt obtained through the isomerization-crystallization process with an acetylating reagent; or (ii) causing the salt obtained through the isomerization-crystallization process with an acid and causing the obtained R-configuration N-benzyl-2-amino-3-methoxypropionamide to react with the acetylating reagent.

5 . The method according to claim 1 , further comprising, an amination process that aminates a compound expressed by a Formula (4) to obtain the racemic N-benzyl-2-amino-3-methoxypropionamide, the amination process being carried out before the isomerization-crystallization process

(where, X represents a leaving group).

6 . A method for producing a salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid or N-formylamino acid, the method comprising causing racemic N-benzyl-2-amino-3-methoxypropionamide to react with the one selected from a group consisting of N-acetylamino acid and N-formylamino acid in a solvent in the presence of an aldehyde compound at a temperature lower than 65° C. to selectively crystallize the salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid or N-formylamino acid.

7 . The method according to claim 6 , wherein an amount of the solvent is 20 mL or less to the racemic N-benzyl-2-amino-3-methoxypropionamide of one gram.

8 . The method according to claim 6 , wherein, in the isomerization-crystallization process, at least one selected from a group consisting of the N-acetylamino acid and the N-formylamino acid is dividedly provided.

9 . A method for producing lacosamide comprising causing the salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid to react with an acetylating reagent in a simple water solvent or an aqueous solution in a presence of a base.

10 . A method for producing lacosamide comprising:
causing the salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid or N-formylamino acid to react with an acid in a solvent to separate the R-configuration of N-benzyl-2-amino-3-methoxypropionamide from N-acetylamino acid or N-formylamino acid; and causing the obtained R-configuration of N-benzyl-2-amino-3-methoxypropionamide to react with an acetylating reagent.

11 . A crystal of a salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid or N-formylamino acid.

12 . The crystal according to claim 11 , wherein the salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-acetylamino acid has a powder X-ray diffraction measuring pattern using a CuKα ray exhibiting peaks at diffraction angels (2θ±0.2°)=6° to 7.5°, 14.5° to 16°, 17.5° to 19°, and 24.5° to 26°.

13 . The crystal according to claim 11 , wherein the salt of R-configuration of N-benzyl-2-amino-3-methoxypropionamide and N-formylamino acid has a powder X-ray diffraction measuring pattern using a CuKα ray exhibiting peaks at diffraction angels (2θ±0.2°)=9° to 10.5°, 11.5° to 13°, 17.5° to 19°, and 24.5° to 26°.

14 . A pharmaceutical composition comprising:
lacosamide produced in a method defined in claim 1 ; and a vehicle pharmacologically acceptable to be mixed with the lacosamide.

15 . A pharmaceutical composition comprising:
lacosamide produced in a method defined in claim 9 ; and a vehicle pharmacologically acceptable to be mixed with the lacosamide.

16 . A pharmaceutical composition comprising:
lacosamide produced in a method defined in claim 10 ; and a vehicle pharmacologically acceptable to be mixed with the lacosamide.

Assignees

• Api Corp

Inventors

• Nagahama Masaki

Classifications

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• C07B57/00

  Separation of optically-active compounds · CPC title

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title

• C07K5/0606 Primary

  the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr · CPC title