Process for the preparation[2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethy l]phosphonic acid
US6011168A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Aug 16, 1999 |
| Grant date | Jan 4, 2000 |
| Priority date | — |
| Expiry date | Aug 16, 2019 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07F9/645
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
This invention relates to a process for the preparation of the formula I compound [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid, a NMDA antagonist useful as an anticonvulsant and neuroprotectant in situations involving excess release of excitatory amino acids. ##STR1## 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]prosphonic acid dialkyl ester (c) in 58% yield. The phosphonic acid diethyl ester (c) was treated with bromotrimethylsilane to give compound I.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.