Naratriptan Hydrochloride

121679-20-7

143388-64-1

General procedure for the synthesis of N-methyl-2-(3-(1-methylpiperidin-4-yl)-1H-indol-5-yl)ethane-1-sulfonamide hydrochloride from N-methyl-3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indole-5-ethane sulfonamide: 1. Compound VIII (50 g, 1501 mmol) was dissolved in a mixed solvent of methanol and acetic acid (0.2L:0.2L) and 2.5 g of platinum oxide catalyst was added. The hydrogenation reaction was carried out at 50 to 60°C for 6 to 8 hours under 5 kg/cm2 hydrogen pressure. After completion of the reaction, the reaction mixture was filtered and distilled to remove the solvent to obtain an oily product. 2. The above oily product was vaporized with isopropanol, followed by addition of 125 ml of ethanolic hydrochloric acid solution and refluxing the reaction mixture for 1 hour. The solid was stirred at 5 to 20°C for 1 hr to precipitate, filtered and washed with cold ethanol to give N-methyl-2-(3-(1-methylpiperidin-4-yl)-1H-indol-5-yl)ethane-1-sulfonamide hydrochloride (I). [Yield 50 g, 89.76%]. 3. Compound I (50 g, 1347 mmol) was dissolved in a mixed solvent of 400 ml of ethanol and 100 ml of water and 2 g of activated carbon was added. It was refluxed at 78-80°C for half an hour. After completion of the reaction, it was filtered through hyflow and washed with 100 ml of ethanol. The filtrate was stirred at 5 to 20°C for half an hour to precipitate a solid, filtered, washed with cold ethanol and dried. [Yield 42.5 g, 85%]. Purity: 99.8%.