Methods of preparing imidazole-based bicyclic compounds
View Patent ↗Methods of preparing compounds of formula I are disclosed:
1. A method of preparing (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol:
which comprises:
combining isoxazole-3-carbonitrile with a first solvent and a first base to provide a first reaction mixture;
combining the first reaction mixture with fructosamine to provide a second reaction mixture; and
isolating (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol from the second reaction mixture.
2. The method of claim 1 , wherein the second reaction mixture further comprises a second base.
3. The method of claim 1 , wherein the first solvent is methanol.
4. The method of claim 2 , wherein the first base is the same as the second base.
5. The method of claim 1 , wherein the first base is methoxide.
6. The method of claim 4 , wherein the first base and the second base are both methoxide.
7. The method of claim 1 , wherein the first reaction mixture is stirred for less than about 48 hours.
8. The method of claim 1 , wherein the first reaction mixture is maintained at a temperature of from about 10 to about 30° C.
9. The method of claim 1 , wherein the second reaction mixture is stirred for less than about 48 hours.
10. The method of claim 1 , wherein the second reaction mixture is maintained at a temperature of from about 10 to about 30° C.
11. The method of claim 1 , wherein the isoxazole-3-carbonitrile is prepared by contacting 5-ethoxy-4,5-dihydroisoxazole-3-carbonitrile with a base in a second solvent to provide a third mixture.
12. The method of claim 11 , wherein the second solvent is tetrahydrofuran or dichloromethane.
13. The method of claim 11 , wherein the third mixture is stirred at a temperature of from about −5 to about 10° C.
14. The method of claim 11 , wherein the third mixture is stirred for less than about 10 hours.