Synthesis of 4-amino-thalidomide and its enantiomers that are suitable for inhibiting angiogenesis

摘要

A method of preparing S(-)-4-amino-thalidomide comprising: (a) contacting 3-nitrophthalic anhydride with S(-)-2-amino-glutarimide hydrobromide under conditions sufficient to form S(-)-4-nitro-thalidomide; and (b) reducing the S(-)-4-nitro-thalidomide under conditions sufficient to form S(-)-4-amino-thalidomide is disclosed; and similarly a method of preparing R(+)-4-amino-thalidomide comprising: (a) contacting 3-nitrophthalic anhydride with R(+)-2-amino-glutarimide hydrobromide under conditions sufficient to form R(+)-4-nitro-thalidomide; and (b) reducing the R(+)-4-nitro-thalidomide under conditions sufficient to form R(+)-4-amino-thalidomide is disclosed. These compounds are suitable for inhibiting angiogenesis and treating angiogenesis-associated diseases, including cancer and macular degeneration.