Methods for the production of C-8 lactam lactone compounds
AssigneeNovartis AG
InventorGottfried Sedelmeier
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Abstract
The invention related to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially renin inhibitors, such as Aliskiren, the invention relates to a process for the manufacture of a compound of the formula I, or a salt thereof, wherein R1 as well as Act are as defined in the specification, and processes of manufacturing this compound as well as intermediates in this process.
Claims39
A process for preparing a compound of formula (V),
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl, or a salt thereof, said process comprising an organocatalytic nitro-Michael addition reaction of nitroethylene or a precursor thereof of formula (XII), or salts thereof,
- wherein —O-LG is a leaving group that is eliminated under the reaction conditions to reveal nitroethylene,
- with a compound of formula (IV), or salt thereof,
- wherein
- R1 is hydrogen, C1-7 alkyl, C3-8 cycloalkyl or benzyl;
- R2 and R3 together with N form a chiral amine moiety.
A process for preparing a compound of formula (VII),
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl and PG is a hydroxyl protecting group, or a salt thereof, said process comprising protecting the hydroxyl functionality of a compound of formula (VI), or salt thereof,
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl, with a protecting group.
A compound of formula (VII),
- wherein
- R1 is isopropyl;
- PG is a hydroxyl protecting group;
- or a salt thereof.
The compound of formula (VIII)
- wherein R1 is isopropyl and PG is benzyl.
A compound of formula (IX),
- wherein
- R1 is isopropyl;
- R5 is hydrogen or PG;
- PG is a hydroxyl protecting group and whereby both PG's can be the same or different;
- or a salt thereof.
A compound of formula (X),
- wherein
- R1 is isopropyl;
- and
- Act is an activating group selected from an amino protecting group, in particular one that together with N forms a carbamate,
- or a salt thereof.
A process for preparing a compound of formula (VIII),
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl and PG is as defined for a compound of formula (VII), or a salt thereof, said process comprising reduction of the nitrile functionality of a compound of formula (XIV),
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl, and PG is as defined for a compound of formula (VII), or a salt thereof,
- into an aldehyde functionality.
A compound of the formula (XVI)
- wherein
- both R1's are the same or different from each other and are hydrogen, C1-7alkyl;
- R8 is C1-7alkyl;
- PG is a hydroxyl protecting group;
- or a salt thereof.
A compound of the formula (XVII)
- wherein
- both R1's are the same or different from each other and are hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl;
- or a salt thereof.
A compound of formula (I), or salt thereof, having one of the following structures:
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl and Act is an activating group selected from an amino protecting group, in particular one that together with N forms a carbamate.
A compound of formula (I), or salt thereof, having one of the following structures:
- wherein Act is an activating group selected from an amino protecting group, in particular one that together with N forms a carbamate.
A compound of formula (V),
- wherein
- R1 is isopropyl or a salt thereof.
A compound of formula (VI),
- wherein
- R1 is isopropyl
- or a salt thereof.
A compound of formula (XVIII)
- having one of the following structures:
- wherein R1 is hydrogen, C1-7alkyl, C3-8cycloalkyl or benzyl.
Dependencies are inferred from the claim text.