Method for preparation of sugammadex sodium
The present invention provides a method for improved preparation of Sugammadex sodium.
1. A method for preparation of Sugammadex sodium, comprising:
(a) reacting gamma-cyclodextrin with tri-n-butylphosphine and X 2 in an organic solvent to obtain a compound of Formula I,
wherein X is F, Cl, Br, or I;
(b) reacting the compound of Formula I with methyl 3-mercaptopropionate in presence of alkali metal hydride in an organic solvent at a temperature lower than 0° C. to obtain a compound of Formula II, and
(c) reacting the compound of Formula II with sodium hydroxide to form the Sugammadex sodium.
2. The method of claim 1 , wherein X 2 -is-bromine and X is Br.
3. The method of claim 1 , wherein the alkali metal hydride is sodium hydride.
4. The method of claim 1 , wherein the organic solvents in step (a) and step (b) are dimethylformamide.
5. The method of claim 1 , which further comprises washing the compound of Formula I in step (a) with an alcohol.
6. The method of claim 5 , wherein the alcohol is isopropanol.
7. The method of claim 5 , which further comprises purifying the compound of Formula I by recrystallization from a solution comprising dimethylformamide and isopropanol before step (b).
8. The method of claim 1 , which further comprises purifying the compound of Formula II by recrystallization from a solution comprising acetonitrile and water before step (c).
9. The method of claim 1 , which further comprises adding alcohol to the Sugammadex sodium.
10. The method of claim 9 , which further comprises purifying the Sugammadex sodium by recrystallization from a solution comprising methanol and water.
11. The method of claim 1 , which further comprises purifying the Sugammadex sodium by a column packed with anion exchange resin.
12. The method of claim 1 , which further comprises desalting the Sugammadex sodium by a group consisting of reverse osmosis (RO) membrane filtration, tangential flow filtration, or column filtration.
13. The method of claim 1 , which further comprises spray drying the Sugammadex sodium to obtain an amorphous powder of the Sugammadex sodium.