Process for the manufacture of 4-aminobenzoamidine dihydrochloride

Patent metadata

Field	Value
Publication number	US-9399616-B2
Application number	US-201314055054-A
Country	US
Kind code	B2
Filing date	Oct 16, 2013
Priority date	Oct 22, 2012
Publication date	Jul 26, 2016
Grant date	Jul 26, 2016

Abstract

The present invention relates to a process for the preparation of 4-aminobenzoamidine (4-AMBA) salts of general formula (I)

preferably the salts thereof with hydrochloric or hydrobromic acid, particularly preferred the dichloride salt.

First claim

We claim:

1. A process for the preparation of a compound of formula (I),

wherein n is 1 or 2 and X is Cl or Br, wherein the process comprises reaction step (B):
(B) treating compound (II) with an alcoholic solution of ammonia,

wherein R is methyl, ethyl, propyl, or butyl, and X is Cl or Br.

2. The process for the preparation of a compound of formula (I) according to claim 1 , wherein the process comprising reaction steps (A) and (B):
treating 4-aminobenzonitril (III) with HX in a pure or mixed alcoholic solvent at a reaction pressure of about 0 to 10 atm

to form compound (II)

wherein if R is ethyl, the reaction pressure is between 2 to 6 atm.

3. A process for the preparation of a compound of formula (I),

wherein n is 1 or 2, and X is Cl or Br, wherein the process comprises reaction steps (A), (B), and (C):
treating 4-aminobenzonitril (III) with HX in a pure or mixed alcoholic solvent at a reaction pressure of about 0 to 10 atm

to form compound (II)

wherein if R is ethyl, the reaction pressure is between 2 to 6 atm;
treating compound (II) with an alcoholic solution of ammonia, wherein R is methyl, ethyl, propyl, or butyl, and X is Cl or Br; and (C) precipitating compound (I) by acidification with aqueous HX, wherein the steps (A), (B) and (C) take place successively in the order specified.

4. The process for the preparation of a compound of formula (I) according to one of claims 1 to 3 , wherein the alcoholic solvent or alcoholic solution is ethanolic or methanolic.

5. The process for the preparation of a compound of formula (I) according to one of claims 1 to 3 , wherein the alcoholic solvent or alcoholic solution is methanolic.

6. The process according to claim 3 , wherein the alcoholic solvent or alcoholic solution in steps (A), (B), is the same and is ethanolic or methanolic.

7. The process according to one of claims 1 to 3 , wherein the HCl or HBr in step (A) or step (B) is in a concentration from 5% to 30% (weight %) in alcohol.

8. The process according to one of claims 2 to 3 , wherein a molar ratio of HCl or HBr to compound (III) is from 2:1 to 20:1.

9. The process according to one of claims 2 to 3 wherein the reaction according to step (A) is conducted at a temperature from −10° C. to 80° C.

10. The process according to one of claims 1 to 3 , wherein the step (B) is run at the temperature from 20° C. to 80° C.

11. The process according to one of claims 1 to 3 , wherein the reaction is run in NH 3 in an alcohol solution with a concentration of NH 3 from 5% to 30% (weight %).

12. The process according to one of claims 1 to 3 , wherein the molar ratio of NH 3 to compound (II) is from 2:1 to 20:1.

Assignees

• Dong Weitong
• Hemp Christian Wolfgang
• Jin Xiangle
• Lu Jun
• Scholz Ulrich
• Su Shengmin
• Xu Wei
• Yang Jinsong
• Boehringer Ingelheim Int

Inventors

• Dong Weitong
• Hemp Christian Wolfgang
• Jin Xiangle
• Lu Jun
• Scholz Ulrich
• Su Shengmin
• Xu Wei
• Yang Jinsong

Classifications

• C07C257/18

  having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07C249/02 Primary

  of compounds containing imino groups · CPC title

• C07C257/08 Primary

  having carbon atoms of imino-carboxyl groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07C213/00 Primary

  Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton · CPC title

• C07C217/76

  having amino groups bound to carbon atoms of six-membered aromatic rings and etherified hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton · CPC title