Methods of preparing Tecovirimat

1. A method for producing N-[(3aR,4R,4aR,5aS,6S,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide, said method comprising:

(a) reacting maleic anhydride (compound 2) and tert-butyl carbazate (compound 5) to form compound 10 of formula:

(b) reacting compound 10 with an acid to form compound 11 or salt thereof of formula:

(c) reacting compound 11 with 4-(trifluoromethyl)benzoyl halide (compound 8) to form compound 9 of formula:

(d) reacting compound 9 with cycloheptatriene (compound 1); and

(e) collecting N-[(3aR,4R,4aR,5aS,6S,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide.

2. The method of claim 1 , wherein step (a) is carried out in anhydrous toluene under nitrogen atmosphere and reactants heated to reflux.

3. The method of claim 1 , wherein said acid in step (b) is HCl.

4. The method of claim 1 , wherein compound 10 is dissolved in i-PrOAc prior to the reaction of step (b).

5. The method of claim 1 , wherein a base is present in the reaction of step (c), wherein said base is selected from the group consisting of: pyridine, 4-dimethylaminopyridine, triethylamine and diisopropylethylamine.

6. The method of claim 1 , wherein said 4-(trifluoromethyl)benzoyl halide is 4-(trifluoromethyl)benzoyl chloride.

7. The method of claim 1 , wherein step (c) is carried out at a temperature of about 10 to about 25° C.

8. The method of claim 1 , wherein step (d) is carried out in toluene under nitrogen atmosphere at a temperature above about 110° C.

9. The method of claim 1 , wherein said N-[(3aR,4R,4aR,5aS,6S,6aS)-3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindol-2(1H)-yl]-4-(trifluoromethyl)-benzamide collected in step (e) is further purified by column chromatography.