| 摘要 |
The invention relates to process for the preparation of 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulphonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazole[4,3-d]pyrimidin-7-one (V) and its pharmaceutically acceptable salts, comprising of the following steps: a) reacting 4-amino-1-methyl-3-n-propylpyrazole-5-carboxamide (I) with hydrogen chloride in a solvent such as isopropanol to give 1-methyl-4-amino-3-n-propylpyrazole-5-carboxamide hydrochloride (II) b) reacting compound II with 2-ethoxybenzoic acid in the presence of phosphorous oxychloride and dimethylformamide to give 4-(2-ethoxybenzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide (III) c) cyclisation of compound III with anhydrous 2-ethoxyethanol in the presence of sodium hydroxide and tetrabutylammonium bromide in catalytic amountsto obtain 5-[2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazole[4,3-d] pyrimidin-7-one (IV) d) reacting compound IV in anhydrous conditions with 4-methylpiperazin-1-sulfamoyl chloride hydrochloride in the presence of anhydrous aluminium chloride to give 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulphonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazole[4,3-d]pyrimidin-7-one (V), which can be converted to its pharmaceutically acceptable salts such as hydrochloride, hydrobromide, sulphate or bisulphate, phosphate or acid phosphate, acetate, citrate, fumarate, gluconate, lactate, meleate, succinate or tartarate.
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