Back to results
US 2014/0179947 A1Published application
Process for manufacture and resolution of 2-acylamino-3-diphenylpropanoic acid
AssigneeZhejiang Jiuzhous Pharmaceutical Co., Ltd.
InventorsGuoliang Zhu, Lijun Yang, Ying Lin, Jie Ying
Life of this patent
Estimating the term…
Abstract
The invention relates to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, in particular neutral endopeptidase (NEP) inhibitors.
Claims23
A process for preparing a compound of formula (I), or salt thereof,
- wherein
- R1 is C1-7alkyl or is substituted or unsubstituted C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S),
- comprising the steps of
- i) preparing in a one-step reaction a compound of formula (III) or salt thereof,
- wherein
- R1 is as defined for the compound of formula (I);
- by reacting a compound of formula (IV), or salt thereof,
- wherein
- R1 is as defined for the compound of formula (I);
- under decarboxylation reaction conditions to provide the compound of formula (III);
- ii) treating the obtained compound of formula (III) or a salt thereof
- with a chiral amine of formula (V)
- wherein
- R2 is C1-7alkyl;
- or is R3R4NC(═O)— or R5OC(═O)—, wherein R3 and R4 are independently selected from hydrogen or C1-7alkyl;
- and R5 is C1-7alkyl;
- R6 is C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S);
- and resolving the resulting diastereomeric mixture via crystallization
- to provide a compound of formula (II)
- wherein
- R1 is as defined for the compound of formula (I);
- R2 is C1-7alkyl;
- or is R3R4NC(═O)— or R5OC(═O)—, wherein R3 and R4 are independently selected from hydrogen or C1-7alkyl;
- and R5 is C1-7alkyl;
- R6 is C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S);
- and
- iii) treating the obtained compound of formula (II),
- with an acidic reagent to provide the compound of formula (I).
28 more elements
A process for preparing a compound of formula (I), or salt thereof,
- wherein
- R1 is C1-7alkyl or is substituted or unsubstituted C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S),
- comprising the steps of
- i) treating a compound of formula (III) or a salt thereof
- wherein
- R1 is as defined for the compound of formula (I);
- with a chiral amine of formula (V)
- wherein
- R2 is C1-7alkyl;
- or is R3R4NC(═O)— or R5OC(═O)—, wherein R3 and R4 are independently selected from hydrogen or C1-7alkyl;
- and R5 is C1-7alkyl;
- R6 is C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S);
- and resolving the resulting diastereomeric mixture via crystallization
- to provide a compound of formula (II)
- wherein
- R1 is as defined for the compound of formula (I);
- R2 is C1-7alkyl;
- or is R3R4NC(═O)— or R5OC(═O)—, wherein R3 and R4 are independently selected from hydrogen or C1-7alkyl;
- and R5 is C1-7alkyl;
- R6 is C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S);
- and
- ii) treating the obtained compound of formula (II),
- with an acidic reagent to provide the compound of formula (I).
23 more elements
A method for preparing a compound of formula (I), or salt thereof,
- wherein
- R1 is C1-7alkyl or is substituted or unsubstituted C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S),
- comprising
- treating a compound of formula (II),
- wherein
- R1 is as defined for the compound of formula (I);
- R2 is C1-7alkyl;
- or is R3R4NC(═O)— or R5OC(═O)—, wherein R3 and R4 are independently selected from hydrogen or C1-7alkyl;
- and R5 is C1-7alkyl;
- R6 is C6-10aryl, and
- “*” means a chiral center with absolute stereochemistry (R) or (S);
- and
- with an acidic reagent
- to provide the compound of formula (I).
12 more elements
A method for preparing a compound of formula (III), or salt thereof,
- in a one step reaction wherein
- R1 is C1-7alkyl, or is substituted or unsubstituted C6-10aryl;
- consisting of
- reacting a compound of formula (IV), or salt thereof,
- wherein R1 is as defined for the compound of formula (III),
- under decarboxylation reaction conditions
- to provide the compound of formula (III).
4 more elements
Dependencies are inferred from the claim text.