Isavuconazonium salts and process for preparing thereof

Patent metadata

Field	Value
Publication number	US-12570649-B2
Application number	US-202017638102-A
Country	US
Kind code	B2
Filing date	Aug 17, 2020
Priority date	Aug 26, 2019
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

The present invention relates to the process of preparation of salts of compound of formula (1).

First claim

The invention claimed is:

1 . A process for preparation of a salt of compound of formula (1) comprising:

a) reacting compound of formula (2) with a first acid HA 1 to obtain compound (3):

X means Cl or Br or I;
A 1 − means an anion originated from the first acid HA 1 ;
b) reacting compound of formula (3) with a second acid HA 2 in a water immiscible solvent to obtain a mixture comprising compound (4) in the water immiscible solvent:

A 2 − means an anion originated from the second acid HA 2 .

2 . The process according to claim 1 wherein the salt of compound of formula (1) is a salt with an acid of formula CX 3 (CX 2 ) m COOH, m is between 0 and 7 and X is selected from H or Cl or F.

3 . The process according to claim 2 wherein the acid is CF 3 COOH.

4 . The process according to claim 1 wherein a solution comprising water immiscible solvent and compound of formula (2) is extracted with a water solution of an acid having pH between 1 and 6 and ionic strength between 0.5 mol/l and 2 mol/l before reacting in step a).

5 . The process according to claim 4 wherein the acid is selected from H 3 PO 4 or formic acid or acetic acid or citric acid.

6 . The process according to claim 1 wherein the water immiscible solvent in step b) is selected from an acetate or an alkane or an ether or toluene or a halogenated alkane.

7 . The process according to claim 1 wherein the process further comprises extracting of the mixture obtained in step b) with water at pH between 1 and 6.

8 . The process according to claim 1 wherein the first acid HA 1 is selected from HCl or HBr or HI.

9 . The process according to claim 1 wherein the second acid HA 2 is CX 3 (CX 2 ) m COOH, m is between 0 and 7 and X is selected from H or Cl or F.

10 . The process according to claim 1 further comprising contacting the compound (4) in a water immiscible solvent with a third acid HA 3 wherein pK a of HA 3 <pK a of HA 2 to obtain a salt of compound of formula (1) with HA 3 .

11 . The process according to claim 10 wherein the third acid HA 3 is selected from H 2 SO 4 or HCl or HBr or H 3 PO 4 .

12 . The process according to claim 10 wherein the third acid HA 3 is H 2 SO 4 and the salt of compound of formula (1) is compound of formula (9):

13 . The process according to claim 12 further comprising contacting the compound of formula (9) with Ba 2+ base to obtain compound of formula (10), Isavuconazonium sulfate:

14 . A process for purification a salt of compound of formula (1) comprising contacting the compound (4)

wherein A 2 − means an anion originated from an acid HA 2 , in a water immiscible solvent with an acid HA 3 wherein pK a of HA 3 <pK a of HA 2 to obtain a salt of compound of formula (1) with HA 3

15 . The process according to claim 14 wherein compound (4) is a salt of compound (1) with an acid of formula CX 3 (CX 2 ) m COOH, m is between 0 and 7 and X is selected from H or Cl or F.

16 . A salt of compound of formula (1)

with an acid of formula CX 3 (CX 2 ) m COOH, m is between 0 and 7 and X is selected from H or Cl or F.

17 . A solid form of the salt of claim 16 .

18 . A pharmaceutical composition comprising the salt according to claim 16 .

Assignees

• Synthon Bv

Inventors

• Bartos Petr

Classifications

• A61P31/10

  Antimycotics · CPC title

• C07D417/14 Primary

  containing three or more hetero rings · CPC title