Characterization of an unstable process impurity in the protease inhibitor Tipranavir

1 Characterization of an unstable process impurity in the protease inhibitor Tipranavir 

While using the 0.1 % threshold as a determinant for when an impurity should be isolated to meet regulatory requirements is a good practice, there are other times when it becomes necessary to work with extraneous compounds at still lower levels. During the development of process chemistry for the synthesis of the protease inhibitor Tipranavir several synthetic lots of the drug were discolored, appearing pinkish rather than white as they should. It was determined that a low-level ( 0.1%) highly colored material was responsible for the problem with those lots and a request for the isolation and characterization of that contaminant was received [66]. 

The methanol solution containing the colored impurity was bright red and provided the feedstock used for preparative chromatographic isolation of the unstable, colored impurity, which had a half life of about 18 h in methanol and 10 m in acetone. Using a 1.7-mm 600-MHz SMIDG probe, which was the most sensitive probe technology routinely available when this work was done in 1999 [49, 59], a sample was prepared and a data set consisting of a proton reference 

The deductions drawn from the NMR data were also supported by vibrational data. Prominent vibrational spectral features included an increase in the intensity of the band at 1636 cm , suggesting increased double bond character in the 

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