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Prasugrel Besylate

IP.com Disclosure Number: IPCOM000240516D
Publication Date: 2015-Feb-05
Document File: 9 page(s) / 125K

Publishing Venue

The IP.com Prior Art Database

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Prasugrel is an oral antiplatelet agent that belongs to the thienopyridine family. It is designed to prevent platelet activation by blocking adenosine diphosphate (ADP) P2Y12 receptors on the platelet surface.

Prasugrel•HCl, chemically known as 5-[(1RS)-2-cyclopropyl-1-(2­fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate hydrochloride and is structurally represented as Formula I. Prasugrel hydrochloride marketed under the brand name of EFFIENT.

WO2009129983, WO 2011057593 and US 20110003847 has been disclosed crystalline salts of Prasugrel sulfonic acid including Prasugrel besylate and crystalline form of the same. The crystalline form of Prasugrel besylate disclosed in these references herein is designated as crystalline Form P of Prasugrel besylate.

We herein provides a novel crystalline Form M of Prasugrel besylate, i.e. 5-[(1RS)-2-cyclopropyl-1-(2­fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate benzene sulfonic acid.

Crystalline Form M of Prasugrel besylate is characterized by the Powder X-ray diffraction having characteristic peaks at 9.34,  17.41,  20.01,  24.03,  25.15 (±) 0.2° 2-theta.

Crystalline Form M of Prasugrel besylate is further characterized by the Powder X-ray diffraction having characteristic peaks at8.14, 9.34, 9.60, 14.28, 17.41, 17.81, 18.81, 20.01, 24.03, 25.15(±) 0.2° 2-theta.

Crystalline Form M of Prasugrel besylate is further characterized by the Powder X-ray diffraction as depicted in Figure 1.

Form M of Prasugrel besylate is further characterized by DSC/DTA thermo gram as depicted in Figure 2.

Form M of Prasugrel besylate is further characterized by TGA/DTA as depicted in Figure 3.

Example 1:

2g of Benzenesulfonic acid was dissolved in 5 ml of acetone at 20-25°C and then added slowly to the suspension of 5g of Prasugrel free base in 10 ml acetone at 20-25°C. The reaction mass was stirred for 10-15 min for complete dissolution. To the clear solution, 5 ml of ethyl acetate was added. The solvent was completely distilled off at 20-25°C under vacuum and foamy solid was obtained. To the reaction mass 15 ml of ethyl acetate was added and stirred for 10-15min at 20-25°C to obtain a clear solution. The reaction mass was further stirred at 20-25°C for 3-4h. The solid obtained was filtered, washed with 10 ml of acetone and dried at 40°C under vacuum for 15h. The resulting product was identified to be crystalline Form M of Prasugrel besylate. Yield: 60% ; HPLC purity (%): 99.90%.

Example 2:

2g of Benzenesulfonic acid was dissolved in 5 ml of acetone at 20-25°C and then added slowly to the suspension of 5g of Prasugrel free base in 10 ml acetone at 20-25°C. The reaction mass was stirred for 10-15 min for complete dissolution. To the clear solution 5 ml of ethyl acetate was added. The solvent was completely distilled off at 20-25°C under vacuum and foamy solid was obtained. To the reaction mass 15 ml of ethyl acetate was added and stirred for 10-15mi...