Method of preparing retroviral protease inhibitor intermediates
AssigneeG.D. Searle & Co.
InventorsJohn S Ng, Claire A Przybyla, Shu-Hong Zhang
Life of this patent
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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.
Claims11
A diastereomer purification method comprising
- (a) preparing an organic acid salt or inorganic acid salt of an amino compound of formula
- wherein
- 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 organic acid salt or said inorganic acid salt from a solution.
A diastereomer purification method comprising
- (a) preparing an acetic acid salt, an oxalic acid salt, or a hydrochloric acid salt of an amino compound of formula
- wherein
- 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 acetic acid salt, said oxalic acid salt, or said hydrochloric acid salt from a solution.
An organic acid salt or an inorganic acid salt of a compound of the formula
- wherein
- 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.
Dependencies are inferred from the claim text.