Details for Patent: 9,045,418
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Title: | Compounds, compositions and methods for treatment and prevention of Orthopoxvirus infections and associated diseases |
Abstract: | Methods of using di, tri, and tetracyclic acylhydrazide derivatives and analogs, as well as pharmaceutical compositions containing the same, for the treatment or prophylaxis of viral infections and diseases associated therewith, particularly those viral infections and associated diseases caused by the orthopoxvirus. |
Inventor(s): | Jordan; Robert (Corvallis, OR), Bailey; Thomas R. (Phoenixville, PA), Rippin; Susan R. (Wilmington, DE), Dai; Dongcheng (Corvallis, OR) |
Assignee: | SIGA TECHNOLOGIES, INC. (Corvallis, OR) |
Filing Date: | Jul 03, 2014 |
Application Number: | 14/323,587 |
Claims: | 1. A process for producing N-[(3aR,4S,4aS,5aR,6R,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-et- henocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide comprising the steps of: (a) reacting 4-trifluoromethylbenzhydrazide with a compound of formula ##STR00055## in a solvent to form a reaction product; and b) collecting N-[(3aR,4S,4aS,5aR,6R,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-et- henocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide. 2. The process of claim 1, wherein the ratio of compound 1(b) to 4-trifluoromethylbenzhydrazide is 0.89 to 1. 3. The process of claim 1, wherein the solvent is ethanol. 4. The process of claim 1, wherein the reaction occurs at above room temperature. 5. The process of claim 1, wherein the reaction occurs under argon. 6. The process of claim 1, wherein the solvent is removed by evaporation. 7. The process of claim 1, wherein N-[(3aR,4S,4aS,5aR,6R,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-et- henocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide is further purified by chromatography. 8. A method of making N-[(3aR,4S,4aS,5aR,6R,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-et- henocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide, said method comprising: a) reacting cycloheptatriene and maleic anhydride in a first solvent to form a compound of formula ##STR00056## b) collecting compound 1(b); c) reacting 4-trifluoromethylbenzhydrazide with said compound 1(b) in a second solvent to form N-[(3aR,4S,4aS,5aR,6R,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-et- henocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide; and d) collecting N-[(3aR,4S,4aS,5aR,6R,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-et- henocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide. 9. The method of claim 8, wherein said first solvent comprises xylenes. 10. The method of claim 8, wherein said second solvent is ethanol. |