US 7,524,960 B2
Highly pure cilostazol and an improved process for obtaining same
Vladimir Naddaka, Lod (Israel); Guy Davidi, Even-Yehuda (Israel); Shady Saeed, Haifa (Israel); Oded Arad, Rechovot (Israel); and Joseph Kaspi, Givatayim (Israel)
Assigned to Chemagis Ltd., Bnei-Brak (Israel)
Filed on Mar. 16, 2005, as Appl. No. 11/80,460.
Claims priority of provisional application 60/553140, filed on Mar. 16, 2004.
Prior Publication US 2005/0222202 A1, Oct. 06, 2005
Int. Cl. C07D 215/38 (2006.01)
U.S. Cl. 546—158 24 Claims
 
1. A process of preparing 6-(4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy)-3,4-dihydro-2(1H)-quinolinone (Cilostazol), the process comprising:
reacting 6-hydroxy-3,4-dihydroquinolin-2(1H)-one with 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole in the presence of a hydrated inorganic base, to thereby obtain a reaction mixture containing Cilostazol;
isolating the Cilostazol from the reaction mixture;
slurrying the Cilostazol in an organic solvent; and
crystallizing the Cilostazol in the presence of a base, to produce Cilostazol, which is substantially free of N-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butyl]-6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone, and has a purity of at least 99.9%.