CRYSTALLINE FORM OF AN ALKOXYIMIDAZOL-1-YLMETHYL BIPHENYL CARBOXYLIC ACID

摘要

The disclosure relates to a crystalline freebase form of 4'-{ 2-ethoxy-4-ethyl-5-[((S)-2-mercapto-4-methylpentanoylamino)methyl]imidazol-1-ylmethyl} -3'-fluorobiphenyl-2-carboxylic acid; pharmaceutical compositions comprising the crystalline compound, processes and intermediates for preparing the crystalline compound. This crystalline compound is suitable for use in the treatment of diseases such as hypertension and heart failure. The process for preparing said crystalline freebase is also disclosed, which comprises the steps of: (a) (i) treating 4'-{ 2-ethoxy-4-ethyl-5-[((S)-2-mercapto-4- methylpentanoylamino)methyl]imidazol-1-ylmethyl} -3'-fluorobiphenyl-2-carboxylic acid with acetone to complete dissolution; or (ii) treating 4'-{ 2-ethoxy-4-ethyl-5-[((S)-2- mercapto-4-methylpentanoylamino)methyl]imidazol-1-ylmethyl} -3'-fluorobiphenyl-2- carboxylic acid with acetonitrile to complete dissolution; or (iii) deprotecting 4'-{ 5-[((S)-2- acetylsulfanyl-4-methylpentanoylamino)methyl]-2-ethoxy-4-ethylimidazol-1-ylmethyl} -3'-fluorobiphenyl-2-carboxylic acid in methanol, and adding water to complete dissolution; (b) cooling to effect crystallization; and (c) isolating the resulting solids to yield the crystalline freebase.