Back to results
US 2003/0171612 A1Published application
Method of preparing retroviral protease inhibitor intermediates
AssigneeG.D. Searle & Co.
InventorsJohn S. Ng, Claire A. Przybyla, Shu-Hong Zhang
Life of this patent
Estimating the term…
Abstract
Chiral hydroxyethylamine, hydroxyethylurea or hydroxyethylsulfonamide isostere containing retroviral protease and renin inhibitors can be prepared by multi-step syntheses that utilize key chiral amine intermediates. This invention is a cost effective method of obtaining such key chiral amine intermediates enantiomerically, diastereomerically and chemically pure. The method is suitable for large scale (multikilogram) productions. This invention also encompasses organic acid and inorganic acid salts of the amine intermediates.
Claims12
Diastereomer purification method comprising
- (a) preparing an organic acid or inorganic acid salt of an amino compound of formula
- 25
- wherein R1 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radicals, which are optionally substituted with alkyl, halogen, NO2, OR9 or SR9 radicals, where R9 represents hydrogen, alkyl, aryl or aralkyl radicals;
- R3 represents hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or N-mono- or N,N-disubstituted aminoalkyl radicals, wherein said substituents are alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, or heterocycloalkylalkyl radicals, or in the case of a disubstituted aminoalkyl radical, said substituents along with the nitrogen atom to which they are attached form heterocycloalkyl or heteroaryl radicals;
- and
- p1 and p2 are each independently hydrogen, acyl, aralkyl, silyl, aralkoxycarbonyl, alkoxycarbonyl, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl or cycloalkenylalkyl radicals;
- or p1 and p2 together with the nitrogen atom to which they are bonded form a heterocyclic ring system;
- and
- (b) precipitating or crystallizing said salt from a solution.
6 more elements
Diastereomer purification method comprising
- (a) preparing an acetic acid, oxalic acid or hydrochloric acid salt of an amino compound of formula
- 26
- wherein R1 represents alkyl, cycloalkylalkyl or aralkyl radicals, which are optionally substituted with alkyl, halogen, NO2, OR9 or SR9 radicals, where R9 represents hydrogen, alkyl, aryl or aralkyl radicals;
- R3 represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl or aralkyl radicals;
- p1 represents benzyl radical;
- and
- p2 represents benzyl radical;
- or p1 and p2 together with the nitrogen atom to which they are bonded form 2-isoindolinyl radicals;
- and
- (b) precipitating or crystallizing said salt from a solution.
7 more elements
Compound of formula
- 27
- wherein R1 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radicals, which are optionally substituted with alkyl, halogen, NO2, OR9 or SR9 radicals, where R9 represents hydrogen, alkyl, aryl or aralkyl radicals;
- R3 represents hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or N-mono- or N,N-disubstituted aminoalkyl radicals, wherein said substituents are alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, or heterocycloalkylalkyl radicals, or in the case of a disubstituted aminoalkyl radical, said substituents along with the nitrogen atom to which they are attached form heterocycloalkyl or heteroaryl radicals;
- and
- p1 and p2 are each independently hydrogen, acyl, aralkyl, silyl, aralkoxycarbonyl, alkoxycarbonyl, alkylcarbonyl, aralkylcarbonyl, arylcarbonyl or cycloalkenylalkyl radicals;
- or p1 and p2 together with the nitrogen atom to which they are bonded form a heterocyclic ring system;
- and
- wherein said compound is an organic acid or inorganic acid salt.
5 more elements
Dependencies are inferred from the claim text.