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5-(4-[4-(5-cyano-1h-indol-3-yl) butyl]piperazin-1-yl)benzofuran-2-carboxamide salts and solid state forms thereof having improved dissolution profile

IP.com Disclosure Number: IPCOM000235625D
Publication Date: 2014-Mar-13
Document File: 3 page(s) / 120K

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The IP.com Prior Art Database

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5-(4-[4-(5-cyano-1h-indol-3-yl) butyl]piperazin-1-yl)benzofuran-2-carboxamide

salts and solid state forms thereof having improved dissolution profile

    5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide HCl is referred to herein as compound I.

    Disclosed herein after is compound I having improved dissolution profile, as well as process for preparation thereof. This compound may be in crystalline form.

    An improved dissolution profile in relation to compound I is wherein at least about 90% by weight of compound I is dissolved after about 40 minutes and/or at least about 70% by weight of the compound I is dissolved after about 20 minutes. For example, at least about 90% by weight of compound I is dissolved after about 20 minutes.

    Compound I having improved dissolution profile may be obtained by a process comprising adding hydrochloric acid to a suspension of 5-(4-[4-(5-cyano-1H- indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide. The HCl addition may be done at a temperature of about 10ºC to about 15ºC to obtain a mixture. The mixture may be further stirred at a temperature of about 10ºC to about 15ºC to obtain the product, preferably as crystals. The product may be isolated by a drying process such as filter dryer.

Example 1. Preparation of the crystalline form of compound I having an improved dissolution profile

5-(4-(4-(5-cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxamide (form

B as described for example in WO20130078361, 17.5 kg; 39.6 mol) was added to a

500 L glass-lined reactor followed by the addition of tetrahydrofurane (44 L) at room

temperature. Water (175 L) was added drop wise during 53 (20-60) minutes and

suspension was cooled to 12 (10-15) C. The suspension was stirred at

approximately 70 rpm. The 0.25 M hydrochloric acid (198.1 L) was added drop wise

over 120 (120-150) minutes, and reaction mixture was stirred additionally 3 hours at

12 (10-15) C. Crystals were isolated at hastelloy filter dryer...