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A process for the preparation of Raltegravir Potassium salt in crystalline Form-3 and amorphous form.

IP.com Disclosure Number: IPCOM000243081D
Publication Date: 2015-Sep-14
Document File: 2 page(s) / 29K

Publishing Venue

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Abstract

The present invention relates to an improved process for the preparation of anhydrous crystalline Raltegravir Potassium Form-3 and amorphous form of Raltegravir Potassium salt.

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A PROCESS FOR THE PREPARATION OF RALTEGRAVIR POTASSIUM SALT IN CRYSTALLINE FORM-3 AND AN AMORPHOUS FORM

[0001]Raltegravir potassium is chemically known as N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]- amino]ethyl]-6-oxo-4-pyrimidinecarboxamide monopotassium salt.

[0002] The present document discloses a process for the preparation of anhydrous crystalline Raltegravir potassium Form 3 comprising the steps of:

a)      suspending or dissolving Raltegravir in a solvent or mixture of solvents;

b)      adding potassium base; and

c)      isolating Raltegravir potassium Form 3.

wherein, potassium base comprises potassium hydroxide, potassium bicarbonate, potassium carbonate, potassium tert- butoxide, potassium alcoholate or mixture thereof. Said potassium base can be added in solution form or as a solid. The isolation is done by cooling the reaction mass to ambient temperature. Solvent include ethanol, water, methanol and the like.

 

[0003] The present document discloses a process for the preparation of an amorphous Raltegravir potassium comprising the steps of:

a)      suspending or dissolving Raltegravir in a solvent or mixture of solvents;

b)      adding potassium base; and

c)      removing the solvent from the solution as obtained in step b), by spray drying; and

d)     isolating amorphous Raltegravir potassium.

wherein, the solvent comprises alcohol, ether or mixtures thereof.

Thus the present invention provides robust process for the preparation of Form 3 as described in US 7,754,731 and amorphous form of Raltegravir potassium.

EXAMPLE-1: Preparation of Raltegravir Potassium crystalline polymorphic Form-3.

Raltegravir (10 gm) was suspended in ethanol (100 ml) and heated to 35-40°C.Tert-Butoxide solution (prepared by dissolving 2.52 gm of Potassium tert-butoxide in 10 ml of ethanol, 1mole equivalent) was added at 35-40°C.The resultant slurry was cooled to 25-30°C and stirred for 1 hr at 25-30°C. Raltegravir Potassium salt was filtered and washed with ethanol (2×10ml) and dried under reduced pressure at ambient temperature followed by at 50-60°C. The obtained solid was characterized as Raltegravir Potassium...