Process for the Monotopic Preparation of Intermediate Organo-Iodinated Compounds for the Synthesis of Ioversol

Patent metadata

Field	Value
Publication number	US-2021284597-A1
Application number	US-201917265107-A
Country	US
Kind code	A1
Filing date	Aug 2, 2019
Priority date	Aug 2, 2018
Publication date	Sep 16, 2021
Grant date	—

Abstract

The invention relates to a process for the preparation of organo-iodinated compounds as well as the preparation intermediates thereof. More specifically, the invention relates to a process for the preparation of organo-iodinated compounds useful as preparation intermediates in the synthesis of the contrast product ioversol.

First claim

1 - 17 . (canceled)

18 . 1. A process for preparing an organo-iodinated compound, comprising the following steps:
a) acylating 2,4,6-triiodo-5-aminoisophthalic acid of formula (A) below:

to obtain an intermediate compound Ya;

b) chlorinating the intermediate compound Ya to obtain an organo-iodinated intermediate compound Yb;
c) amidating the organo-iodinated intermediate compound Yb to obtain an intermediate compound Yc; and
d) deprotecting the intermediate compound Yc,
the steps a), b), c) and d) being carried out without isolation of at least one intermediate compound chosen from Ya and Yc

19 . The preparation process of claim 18 , wherein:
the 2,4,6-triiodo-5-aminoisophthalic acid is acylated by a compound of general formula (I) below:
R 2 —C(O)Cl  (I),

wherein R 2 is a —CH 2 -GP group, wherein GP is a leaving group selected from the group consisting of a halide, an acetate, a mesylate, a tosylate, and a triflate; and
the organo-iodinated intermediate compound Yb corresponds to general formula (II) below:

wherein R 1 is H or a methyl group.

20 . The preparation process of claim 18 , free of a step of separating the intermediate compound Ya from the reaction medium obtained at the end of step a).

21 . The preparation process of claim 18 , free of a step of separating the intermediate compound Yc from the reaction medium obtained at the end of step c).

22 . The preparation process of claim 18 , wherein R 2 is —CH 2 Cl or

23 . The preparation process of claim 18 , wherein the steps a), b), c) and d) are carried out without isolation of the intermediate compounds Ya and Yc.

24 . The preparation process of claim 18 , wherein the steps a), b), c) and d) are carried out without purification of the intermediate compound Yb.

25 . The preparation process of claim 18 , free of addition of a nonsolvent of the intermediate compound Ya during step a) and between steps a) and b).

26 . The preparation process of claim 18 , wherein the steps a), b), c) and d) are carried out in a single reactor.

27 . The preparation process of claim 18 , wherein the steps a), b), c) and d) are carried out in the presence of a solvent selected from the group consisting of dimethylacetamide, propylene carbonate, acetonitrile, tetrahydrofuran, and mixtures thereof.

28 . The preparation process of claim 18 , wherein the solvent of step b) is a mixture of propylene carbonate and dimethylacetamide.

29 . The preparation process of claim 18 , wherein step c) is carried out in the presence of an aqueous solution.

30 . The preparation process of claim 27 , wherein:
the solvent of step a) is dimethylacetamide; and/or the solvent of step c) and/or of step d) is a mixture of dimethylacetamide and an aqueous solution.

31 . The preparation process of claim 18 , wherein the chlorination of step b) is carried out in the presence of a chlorinating agent selected from the group consisting of thionyl chloride, phosphorus oxychloride, phosphorus trichloride, oxalyl chloride, phosphorus pentachloride, methanoyl dichloride, and mixtures thereof.

32 . The preparation process of claim 18 further comprising:
adding a nonsolvent of the intermediate compound Yb into the reaction medium obtained at the end of step b), whereby the intermediate compound Yb precipitates from the reaction medium and a reaction medium comprising a liquid phase and a precipitate is obtained;
separating the precipitate and the liquid phase; and
dissolving of the separated precipitate in a solvent of the intermediate compound Yb to obtain a solution used to carry out step c).

33 . The preparation process as claimed in claim 18 , wherein the amidation of step c) is carried out with aminopropanediol.

34 . The preparation process as claimed in claim 18 , wherein the deprotection of step d) is carried out with sodium hydroxide, hydrochloric acid, or a mixture thereof.

Assignees

• Guerbet Sa

Inventors

• Stéphan Pellinghelli
• Petta Myriam

Classifications

• C07C233/69

  of an acyclic saturated carbon skeleton · CPC title

• C07C231/02 Primary

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title