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US 8,115,016 B2Granted
Process for preparing 5-biphenyl-4-amino-2-methyl pentanoic acid
AssigneeNovartis AG
InventorsDavid Hook, Thomas Ruch, Bernhard Riss, Bernhard Wietfeld, Gottfried Sedelmeier, Matthias Napp, Markus Bänziger, Steven Hawker, Lech Ciszewski, Liladhar M Waykole
Life of this patent
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Abstract
The present invention relates to pyrrolidin-2-ones according to the formula (1), or salts thereof, wherein R1 is hydrogen or a nitrogen protecting group, methods for their preparation and their use in the preparation of NEP-inhibitors, particularly in the preparation of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.
Claims16
A compound according to formula (1), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group.
A compound according to formula (1′), or salt thereof
- wherein R1 is hydrogen or a nitrogen protecting group and R1 ′ is hydrogen or an oxygen protecting group.
A process for producing a compound according to formula (2), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, comprising methylating a compound according to formula (1), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group.
A process comprising:
- (a) treating a compound of formula (1), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, first with a base and then with a compound of the formula YCO2R, wherein Y is halogen or —OR′ and wherein R and R′ are independently selected from alkyl, aryl and arylalkyl, to obtain a compound of formula (20), or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, R11 is hydrogen and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- b) reacting the resulting compound of formula (20) with a base and a methylating reagent to obtain a compound of formula (20), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- c) optionally, treating the compound of formula (20) wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl, with a saponification reagent, to obtain a compound of formula (20), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OH;
- d) treating the compound obtained in step (b) or (c) under decarboxylation conditions to obtain the compound of formula (2) or tautomer, or salt thereof,
3 more elements
A process comprising:
- (a) treating a compound of formula (1-a), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group first with a base and then with a compound of the formula YCO2, wherein Y is halogen or —OR′ and wherein R and R′ are independently selected from alkyl, aryl and arylalkyl, to obtain a compound of formula (20-a), or salt thereof,
- b) reacting the resulting compound of formula (20-a) with a base and a methylating reagent to obtain a compound of formula (20-a), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- c) optionally, treating the compound of formula (20-a) wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl, with a saponification reagent, to obtain a compound of formula (20-a), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OH;
- d) treating the compound obtained in step (b) or (c) under decarboxylation conditions to obtain the compound of formula (2-a), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group.
3 more elements
A process comprising:
- (a) treating a compound of formula (1-a), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, first with a base and then with a compound of the formula YCO2R, wherein Y is halogen or —OR′ and wherein R and R′ are independently selected from alkyl, aryl and arylalkyl, to obtain a compound of formula (20-a), or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, R11 is hydrogen and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- b) reacting the resulting compound of formula (20-a) with a base and a methylating reagent to obtain a compound of formula (20-a), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- c) optionally, treating the compound of formula (20-a) wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl, with a saponification reagent, to obtain a compound of formula (20-a), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OH;
- d) treating the compound obtained in step (b) or (c) under decarboxylation conditions to obtain the compound of formula (2) or tautomer, or salt thereof,
- wherein the compound according to formula (2) is produced in a ratio of diasteromers (2-a)to (2-b)
- of at least 55:45.
5 more elements
A process comprising:
- (a) treating a compound of formula (1-a), or tautomer, or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, first with a base and then with a compound of the formula YCO2R, wherein Y is halogen or —OR′ and wherein R and R′ are independently selected from alkyl, aryl and arylalkyl, to obtain a compound of formula (20-a), or salt thereof,
- wherein R1 is hydrogen or a nitrogen protecting group, R11 is hydrogen and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- b) reacting the resulting compound of formula (20-a) with a base and a methylating reagent to obtain a compound of formula (20-a), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl;
- c) optionally, treating the compound of formula (20-a) wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OR wherein R is alkyl, aryl or arylalkyl, with a saponification reagent, to obtain a compound of formula (20-a), or salt thereof, wherein R1 is hydrogen or a nitrogen protecting group, R11 is methyl and R10 is OH:
- d) treating the compound obtained in step (b) or (c) under decarboxylation conditions to obtain the compound of formula (2) or tautomer, or salt thereof,
- wherein the compound according to formula (2) is produced in a ratio of diasteromers (2-a)to (2-b)
- of at least 29:79.
5 more elements
Dependencies are inferred from the claim text.