发明名称 |
PROCESS FOR THE PREPARATION OF [2-((8,9)- DIOXO-2,6-DIAZABICYCLO [5.2.0]-NON-1(7)-EN-2-YL)-ETHYL] PHOSPHONIC ACID |
摘要 |
This invention relates to a process for the preparation of formula (I) compound [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid, an NMDA antagonist useful as an anticonvulsant and neuroprotectant in situations involving excess release of excitatory amino acids. In the process of the present invention, 3-aminopropyl carbamic acid 1,1-dimethyl-ethyl ester is reacted with a dialkyl vinylphosphonate to obtain N-[3-(t-butyloxycarbonyl-amino)propyl]-2-aminoethylphosphonic acid dialkyl ester (d) in 80 % yield. Reaction of (d) with a 3,4-dialkoxycyclobut-3-en-1,2-dione gives [3-[[2-(dialkoxyphosphoryl)ethyl]-(2-alkoxy-3,4-dioxo-1,2-cyclobuten-1-yl)amino]propyl] carbamic acid 1,1-dimethylethyl ester (e) in 96 % yield. Deprotection and cyclization of (e) in trifluoroacetic acid gives [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid dialkyl ester (c) in 58 % yield. The phosphonic acid diethyl ester (c) was treated with bromotrimethylsilane to give compound (I). |
申请公布号 |
WO9906417(A1) |
申请公布日期 |
1999.02.11 |
申请号 |
WO1998US15841 |
申请日期 |
1998.07.31 |
申请人 |
AMERICAN HOME PRODUCTS CORPORATION |
发明人 |
ASSELIN, ANDRE, ALFRED;KINNEY, WILLIAM, ALVIN;SCHMID, JEAN |
分类号 |
C07F9/40;C07F9/645;(IPC1-7):C07F9/645 |
主分类号 |
C07F9/40 |
代理机构 |
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代理人 |
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主权项 |
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