Process for the synthesis of melphalan

Patent metadata

Field	Value
Publication number	US-12077484-B2
Application number	US-202318320326-A
Country	US
Kind code	B2
Filing date	May 19, 2023
Priority date	Dec 23, 2019
Publication date	Sep 3, 2024
Grant date	Sep 3, 2024

Abstract

The invention relates to a process for the preparation of Melphalan (4-[bis(2-chloroethyl)amino]-L-phenylalanine of formula (I)

said process comprising the reaction of a 4-amino-L-phenylalanine protected at the carboxy and amino aminoacidic groups with an agent able to convert the aromatic amino group into a group of formula: —N(CH 2 CH 2 OS(O) n O − ) 2 , wherein n is 1 or 2 followed by conversion of the —N(CH 2 CH 2 OS(O) n O − ) 2 group into a —N(CH 2 CH 2 Cl) 2 group.

The invention also provides novel intermediates useful for the preparation of Melphalan.

First claim

The invention claimed is:

1. A compound of formula (IV):

wherein R 1 is a carboxy-protecting group and one of R 2 and R 3 is hydrogen and the other one is an amino protecting group or R 2 and R 3 together with the nitrogen atom they are bound to form an amino-protecting group, X is —OS(O) n O − , wherein n is 1 or 2, and M + or M 2+ is a metallic cation.

2. A compound according to claim 1 wherein R 1 is ethyl, and R 2 and R 3 , together with the nitrogen atom they are bound to, represent a group of formula (VI):

3. A compound according to claim 1 wherein X is —OS(O) 2 O − .

Assignees

• Indena Spa

Inventors

• Allegrini Pietro
• Bonetti Andrea
• Molinari Marco
• Gambini Andrea

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07C227/20 Primary

  by hydrolysis of N-acylated amino-acids or derivatives thereof, e.g. hydrolysis of carbamates · CPC title

• C07D209/48 Primary

  with oxygen atoms in positions 1 and 3, e.g. phthalimide · CPC title