Nuclear transport modulators and uses thereof
Compounds of formula I: and pharmaceutically acceptable salts, solvates, or hydrates thereof, pharmaceutical compositions comprising the compounds of formula I, and methods of making and using the compounds, salts, solvates, or hydrates and the compositions in the treatment of various disorders associated with CRM1 activity.
1. A method of synthesizing (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-pivaloylacrylohydrazide comprising reacting (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid with pivalohydrazide
having a formula of
2. The method of claim 1 , wherein the (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid is formed by reacting (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate with LiOH.
3. The method of claim 2 , wherein the (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate is formed by reacting 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole with (Z)-isopropyl 3-iodoacrylate.
4. The method of claim 3 , wherein the 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole is formed by reacting 3,5-bis(trifluoromethyl)benzothioamide with hydrazine hydrate.
5. The method of claim 4 , wherein the 3,5-bis(trifluoromethyl)benzothioamide is formed by reacting 3,5-bis(trifluoromethyl)benzonitrile with sodium sulfhydrate.
6. A method of synthesizing (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid comprising reacting (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate with LiOH.