发明名称 |
NOVEL SYNTHESIS AND CRYSTALLIZATION OF PIPERAZINE RING-CONTAINING COMPOUNDS |
摘要 |
The present invention is directed to methods for the preparation of piperazine ring-containing compounds, particularly mirtazapine. According to the present invention, the mirtazapine intermediate 1-(3-carboxypyridyl-2)-4-methyl-2-phenyl-piperazine is made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with a base where the base is present in a ratio of up to about 12 moles of the base per one mole of 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine. The mirtazapine intermediate 1-(3-carboxypyridly-2)-4-methyl-2-phenyl-piperazine may be made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with potassium hydroxide at a temperature of at least about 130 DEG C. The method of the present invention also includes reacting 2-amino-3-hydroxymethyl pyridine with N-methyl-1-phenyl-2, 2'-iminodiethyl chloride to form 1-(3-hydroxymethylpyridyl-2)-4-methyl-2-phenyl piperazine, and adding sulfuric acid to the 1-(3-hydroxymethylpyridyl-2)-phenyl-4-methylpiperazine to form mirtazapine. The present invention also relates to new processes for recrystallization of mirtazapine form crude mirtazapine.
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申请公布号 |
WO0062782(A1) |
申请公布日期 |
2000.10.26 |
申请号 |
WO2000US10357 |
申请日期 |
2000.04.18 |
申请人 |
TEVA PHARMACEUTICAL INDUSTRIES LTD.;TEVA PHARMACEUTICALS USA, INC.;SINGER, CLAUDE;LIBERMAN, ANITA;FINKELSTEIN, NINA |
发明人 |
SINGER, CLAUDE;LIBERMAN, ANITA;FINKELSTEIN, NINA |
分类号 |
A61K31/55;A61P25/24;C07D401/04;C07D471/14;(IPC1-7):A61K31/55;C07D487/12 |
主分类号 |
A61K31/55 |
代理机构 |
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代理人 |
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主权项 |
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