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PROCESS FOR THE PREPARATION OF CABERGOLINE POLYMORPHS

IP.com Disclosure Number: IPCOM000147248D
Publication Date: 2007-Mar-06
Document File: 4 page(s) / 36K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to a process for the preparation of amorphous cabergoline. The present disclosure further relates to a process for the preparation of Form VII of cabergoline.

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PROCESS FOR THE PREPARATION OF CABERGOLINE POLYMORPHS

Pranab Chatterjee, Saridi Madhava Dileep Kumar, Swargam Sathyanaryana, Mohan Prasad

Ranbaxy Laboratories Limited, Plot 20, Sector 18, Udyog Vihar, Gurgaon -122001, Haryana, India

Abstract:

The present disclosure relates to a process for the preparation of amorphous cabergoline. The present disclosure further relates to a process for the preparation of Form VII of cabergoline.

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1-[(6-allylergolin-8ß-yl)- carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea, commonly known as cabergoline is a dopamine receptor antagonist.

FORMULA I

Cabergoline is indicated for the treatment of hyperprolactinemic disorders, either idiopathic or due to pituitary adenomas.

GB Patent No 2,074,566 B provides a process for preparing cabergoline, wherein the final product is isolated as a diphosphate salt. J. Org. Chem. 2002, 67, 7147-7150 provides a process for preparing cabergoline as an amorphous solid by concentrating a solution of cabergoline in ethyl acetate. PCT Publication No WO 03/078433 provides a process for preparing a mixture of amorphous cabergoline and Form I, by drying the toluene solvate Form V. PCT Publication No WO 04/094368 provides processes for preparing amorphous cabergoline from tert-butyl methyl ether solvate Form A. PCT Publication No WO 05/085243 provides a process for preparing amorphous cabergoline, wherein the process involves dissolving chromatographically purified oily cabergoline in acetone and partially removing the solvent several times in vacuum. The prior art processes for preparing amorphous cabergoline involve the use of solvated forms or oily form of cabergoline as a starting material.

PCT Publication No WO 01/72746 provides a process for preparing Form VII from Form I by using n-heptane or 1,4-dioxane.

The present

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thors have developed a novel process for preparing amorphous cabergoline, wherein the process does not require the preparation of any solvated cabergoline as a starting substrate. The present process is simple and provides amorphous cabergoline in a single step. By employing the present disclosure, any non-solvated solid form of cabergoline can be converted into amorphous form with more than about 90% yield. The present disclosure also provides a process for preparing Form VII of cabergoline from amorphous cabergoline.

A first aspect of the present disclosure provides a process for the preparation of amorphous cabergoline, wherein the process comprises

a) treating a non-solvated solid form of cabergoline with an organic solvent,

b) removing the solvent from the reaction mixture obtained in step a), and

c) isolating amorphous cabergoline from the reaction mixture thereof.

Any non-solvated solid form of cabergoline known to the person skilled in the art ...