Echothiophate iodide process

Patent metadata

Field	Value
Publication number	US-9708352-B2
Application number	US-201515108790-A
Country	US
Kind code	B2
Filing date	Jan 1, 2015
Priority date	Jan 31, 2014
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

The present invention relates to a process for preparation of Echothiophate Iodide (I). Echothiophate Iodide (I) obtained by the process of the present invention is obtained as new crystalline form designated as Form-SET.

The process for preparation of Echothiophate Iodide (I) according to present invention is an ecofriendly process that avoids the use of hazardous solvent systems and provides Echothiophate Iodide (I) of high purity. Pharmaceutical composition of the said crystalline Form-SET of Echothiophate Iodide (I) of high purity is useful in the treatment of ocular disorders like Glaucoma.

First claim

We claim:

1. A process for preparation of Echothiophate Iodide (I),

comprising the steps of:
a) providing a solution of 2-(dimethylamino) ethane thiol or its salt and a base in an organic solvent;
b) optionally heating the reaction mixture to 50-70° C. and obtaining a residual mass;
c) treating the step a) or b) material with diethyl halogen phosphate in an organic solvent having boiling point greater than 100° C. to obtain S-2-(dimethyl amino) ethyl O,O-diethyl phosphorothioate of Formula (II);

d) reacting S-2-(dimethyl amino)ethyl O,O-diethyl phosphoro thioate (II) of step c) with methyl iodide in an organic solvent; and
e) isolating pure Echothiophate Iodide (I).

2. A process for preparation of Echothiophate Iodide (I) according to claim 1 , wherein organic solvent used in step a) is C 1 -C 3 alcoholic solvent selected from methanol, ethanol or n-propanol and the base is an alkali metal alkoxide.

3. A process for preparation of Echothiophate Iodide (I) according to claim 1 , wherein in step c) diethyl halogen phosphate is selected to be diethylchlorophosphate and solvent with boiling point greater than 100° C. is hydrocarbon solvent selected from toluene or xylene.

4. A process for preparation of Echothiophate Iodide (I) according to claim 1 , wherein organic solvent used in step d) is a nitrile or ketone solvent selected from acetonitrile or acetone.

5. A process for preparation of Echothiophate Iodide (I) according to claim 1 , wherein in step e) isolation of pure Echothiophate Iodide (I) further comprises the steps of:
i. providing a solution of reaction mass obtained from step d) in 2-5 volume C 1 -C 3 alcohol solvent selected from methanol, ethanol or isopropanol;
ii. recovering solvent from reaction mixture to obtain a residue;
iii. treating the residue obtained in step ii. with an ester solvent selected from methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate or methyl propionate; and
iv. isolating the pure Echothiophate Iodide (I).

6. Crystalline Echothiophate Iodide (I), designated as Form-SET characterized by X-ray powder diffraction pattern- having at least five 2θ° peaks selected from the XRPD peak set of 14.4, 15.0, 18.2, 18.7, 21.1, 21.3, 23.3, 25.1and 31.8±0.2θ°.

7. Crystalline Echothiophate Iodide (I) Form-SET, according to claim 6 , further characterized by X-ray powder diffraction pattern- having diffraction angle 2θ° peaks at 16.1, 16.7, 20.4, 22.1, 24.1, 25.8, 26.2, 27.8, 30.6 and 33.5±0.2θ°.

Assignees

• Shilpa Medicare Ltd

Inventors

• Kokare Nagnnath
• Bathula Venkatanarayana
• Chaturvedi Akshaykant

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07F9/202 Primary

  with hydroxyl compounds without further substituents on alkyl · CPC title

• C07F9/17 Primary

  with hydroxyalkyl compounds without further substituents on alkyl · CPC title