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US 10,377,697 B2Granted
Process and intermediates
AssigneeNovartis AG
InventorsFlorian Karl Kleinbeck-Riniker, Benjamin Martin, Gerhard Penn, Francesco Venturoni, Thierry Schlama, Thomas Ruch, Thomas Allmendinger, Bernhard Wietfeld, Paolo Filipponi
Life of this patent
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Abstract
The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.
Claims7
A compound of formula (XV), or a salt thereof
- wherein:
- R5 is selected from the group consisting of hydrogen and a group CO—OR*, and
- Ra and R* are, independently of each other, selected from the group consisting of hydrogen, a carboxyl protecting group, and C1-C6-alkyl.
A process for the manufacture of a compound of formula (I), or a salt thereof;
- wherein:
- Ra is selected from the group consisting of hydrogen, a carboxyl protecting group and C1-C6-alkyl, comprising reacting a compound of formula (II), or a salt thereof,
- wherein:
- Ra and R* are, independently of each other, selected from the group consisting of hydrogen, a carboxyl protecting group, and C1-C6-alkyl, under—if required—deprotection reaction conditions, followed by decarboxylation reaction conditions, and optionally by introduction of a moiety Ra selected from the group consisting of a carboxyl protecting group and C1-C6-alkyl, to provide the compound of formula (I).
1 more element
A process for the manufacture of a compound of formula (I), or a salt thereof;
- wherein:
- Ra is selected from the group consisting of hydrogen, a carboxyl protecting group, and C1-C6-alkyl, comprising reacting an activated dianionic derivate of the compound of formula (V), or a salt thereof,
- with a compound of formula (XIV), or a salt thereof
- wherein:
- Rf is selected from the group consisting of
- —O—R* wherein R* is selected from the group consisting of a carboxyl protecting group and C1-C6-alkyl,
- —N(CH3)—O(CH3),
- morpholinyl, and
- imidazolinyl,
- in the presence of a base, and followed by a decarboxylation reaction, to obtain compound of formula (I), or a salt thereof wherein Ra is hydrogen, optionally followed by reacting the obtained compound of formula (I), or a salt thereof, wherein Ra is hydrogen, with an agent introducing a carboxyl protecting group, to provide the compound of formula (I), wherein Ra is a carboxyl protecting group, and/or
- optionally followed by reacting the compound of the formula (I), or a salt thereof, wherein Ra is hydrogen, with a coupling reagent in the presence of an C1-C6-alkanol, to provide the compound of formula (I), wherein Ra is C1-C6-alkyl.
8 more elements
Dependencies are inferred from the claim text.