Method of producing n-[(2S)-sulfanyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide and intermediate thereof
AssigneeBristol-Myers Squibb Company
InventorsJeffrey T. North, Brian Leslie James
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Abstract
Process for producing N-[(2S)-sulfanyl-4-(1,5,5-trimethylhydantoinyl) butanoyl]-L-leucyl-L-tert-leucine N-methylamide by forming an intermediate compound N-[(2S)-thiobenzoyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide by an improved process that substantially reduces the presence of contaminants in the reaction mixture.
Claims27
A method of producing N-[(2S)-thiobenzoyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide comprising reacting 1,5,5-trimethyl-3-((3S)-thiobenzoyl-3-carboxypropyl)hydantoin and L-leucyl-L-tert-leucine N-methylamide with a base, water and an activating agent in the presence of an aprotic solvent.
A method of forming N-[(2S)-sulfanyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide comprising the steps of:
- a) reacting 1,5,5-trimethyl-3-((3S)-thiobenzoyl-3-carboxypropyl)hydantoin and L-leucyl-L-tert-leucine N-methylamide with a base, water and an activating agent in the presence of an aprotic solvent to form N-[(2S)-thiobenzoyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide;
- and
- b) reacting N-[(2S)-thiobenzoyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide with a debenzoylating agent to produce N-[(2S)-sulfanyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide.
Dependencies are inferred from the claim text.