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Processes For Preparing a Crystalline Form of 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide HCl

IP.com Disclosure Number: IPCOM000227423D
Publication Date: 2013-May-07
Document File: 4 page(s) / 148K

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Processes For Preparing a Crystalline Form of 5-(4-[4-(5-cyano-1H-indol-3- yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide HCl

5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide, has the following chemical structure: Provided are processes for the preparation of crystalline 5-(4-[4-(5-cyano-1H-indol-3- yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide HCl. The obtained crystalline form can be characterized by having XRD peaks at about: 9.08, 12.85, 14.50, 16.89, 18.89, 20.43, 21.72,


24.61, 27.35, 28.18 2θ.

Example 1: 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide base (2,50 g) was suspended in ethanol (25 ml) and heated to 70-75 °C. Solution of hydrochloric acid (prepared by diluting conc. aq. hydrochloric acid with ethanol - cca 0,5 M) was added dropwise until pH < 2 was reached (about 15 ml during 75 min.). The suspension was cooled down to 20-25 °C. Crystals were filtered off, washed with ethanol (10 ml) and dried in open plate at room conditions. Crystals of 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1- yl)benzofuran-2-carboxamide hydrochloride were obtained (2,55 g, yield = 94 %).

Example 2: 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide base (5,0 g) was suspended in ethanol (50 ml) and heated to 70-75 °C. Solution of hydrochloric acid in ethanol (cca 0,6 M) was added dropwise until pH < 2 was reached (about 24 ml during 60 min.). The suspension was cooled down to 20-25 °C. Crystals were filtered off, washed with ethanol (2x10 ml) and dried in open plate at room conditions and additionally at 50°C in vacuum for 6 h. Crystals of 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran- 2-carboxamide hydrochloride were obtained (5,11 g, yield = 95 %).


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Example 3: 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide base (2,0 g) was suspended in isopropanol (40 ml) and heated to 75-80 °C. Solution of hydrochloric acid in isopropanol (cca 0,5 M) was added dropwise until pH < 2 was reached (about 12 ml during 30 min.). The suspension was cooled down to 26 °C. Crystals were filtered off, washed with isopropanol (5 ml) and dried at 50°C in vacuum for 17 h. Crystals of 5-(4-[4-(5-cyano-1H- indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide hydrochloride were obtained (1,99 g, yield = 92 %).

Example 4: 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide base (5,0 g) was suspended in isopropanol (50 ml) and heated to 65-70 °C. Tetrahydrofuran was added in portions until solution was obtained (40 ml). Solution of hydrochloric acid in isopropanol (cca 1 M) was added dropwise until pH < 2 was reached (about 11 ml during 50 min.). The suspension was cooled down to 20-25 °C. Crystals are filtered off, washed with isopropanol (10 ml) and dried in open plate at room conditions overnight and additionally at 50°C in vacuum for 6h. Crystals of 5-(4-[4-(5-cyano-1H-indol-3-y...