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PROCESS FOR THE PREPARATION OF PALBOCICLIB CRYSTALLINE FORMS

IP.com Disclosure Number: IPCOM000246804D
Publication Date: 2016-Jul-01
Document File: 3 page(s) / 815K

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Abstract

THE PRESENT DISCLOSURE RELATES TO PROCESS FOR THE PREPARATION OF PALBOCICLIB CRYSTALLINE FORMS

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PROCESS FOR THE PREPARATION OF PALBOCICLIB CRYSTALLINE FORMS

Palbociclib (codenamed PD-0332991, trade name Ibrance) is a potent and selective inhibitor of CDK4 and CDK6. It is chemically known as 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl) pyridin-2yl] amino} pyrido [2,3-d]pyrimidin-7(8H)-one, represented by formula-1.

Example 1: Preparation of Palbociclib Form-A:

To a stirred suspension of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H- pyrido[2,3-d]pyrimidin-7-one Hydrochloride (50.0 gm) in Isopropanol (500ml,10V) and water (500ml,10.0
V), added aqueous solution of sodium hydroxide (8.26 gm in 100 ml water) at 24-27°C.Reaction mass was stirred for 2 hrs . Filtered the product and wash with water (100.0 ml, 2.0 V) and then washed with Isopropanol (100 ml, 2.0V) and suck dried for 1.0 hrs. The resulting product was dried at 50-55°C under vacuum for 6-8 hrs to give 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H- pyrido[2,3-d]pyrimidin-7-one , 36.0 gm (89%) as a yellow solid (Palbociclib Form-A, Fig.1).

HPLC purity 99.99%; Specific surface area (SSA) - 4.22 m2/g

Fig.1: Powder X-ray diffraction pattern of Palbociclib crystalline Form-A.

1


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Fig.1

Example 2: Preparation of Palbociclib Form-B:

To a stirred suspension of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H- pyrido[2,3-d]pyrimidin-7-one Hydrochloride (50.0 gm) and water (1750 ml,35.0 V) added aqueous solu...