US 6,187,916 B1 · Process for the preparation of taxane derivatives and β-lactam intermediates therefor

Abstract

A process for the preparation of a taxane derivative of the formula in which R2 represents an RO—, RS— or RR′N— in which R represents an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, or cycloalkyl, saturated heterocyclic, cycloalkenyl, unsaturated heterocyclic, aryl or heterocyclic aromatic; R′ is a hydrogen or R defined above; R and R′ can be connected to form together with the nitrogen a cyclic structure; Y is oxygen or sulfur; R3 represents an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, cycloalkenyl or an unsubstituted or substituted aryl; which comprises reacting a β-lactam of the formula in which R311 represents a radical R3 defined above or a protected R3 whenever R3 includes one or more active hydrogens; with a baccatin III derivative of the formula: in which M is an alkali metal or alkaline earth metal atom (ion).

Claims13

Dependent claims

A β-lactam of the formula I:

in which:
R2′ represents RO—, RS—, or RR′N— in which R represents a cycloalkyl, cycloalkenyl, or unsaturated or saturated heterocyclic radical containing 3 to 15 carbon atoms, wherein said heterocyclic radical contains at least one oxygen, nitrogen, or sulfur atom. R′ is hydrogen or R as defined above, or R and R′ are together an alkylene, alkenylene, or alkynylene of 2 to 10 carbons;
R3′ represents a straight-chain or branched alkyl, alkenyl, or alkynyl radical, or a cycloalkyl, cycloalkenyl, or aryl radical;
wherein R and R3′ are unsubstituted or substituted with one or more halogen, hydroxyl, alkoxy, aryloxy, heteroaryloxy, amino, alkylamino, dialkylamino, mercapto, alkylthio, arylthio, heteroarylthio, cyano, carboxyl, alkoxycarbonyl, wherein the alkyl portion contains 1 to 15 carbon atoms, aryloxycarbonyl, wherein the aryl portion contains 6 to 20 carbon atoms, or heteroaryloxycarbonyl radicals, wherein the heteroaryl portion contains 3 to 15 carbon atoms;
G1 represents a hydrogen or a hydroxyl protecting group;
and
Y is oxygen.

4 more elements

A β-lactam of the formula I:

in which:
R2′ represents RO—, RS—, or RR′N— in which R represents a straight-chain or branched alkyl, alkenyl, or alkynyl radical, a cycloalkyl, cycloalkenyl, aryl, or unsaturated or saturated heterocyclic radical containing 3 to 15 carbon atoms, wherein said heterocyclic radical contains at least one oxygen, nitrogen, or sulfur atom, R′ is hydrogen or R as defined above, or R and R′ are together an alkylene, alkenylene, or alkynylene of 2 to 10 carbons;
R3′ represents a cycloalkyl or cycloalkenyl radical;
wherein R and R3′ are unsubstituted or substituted with one or more halogen, hydroxyl, alkoxy, aryloxy, heteroaryloxy, amino, alkylamino, dialkylamino, mercapto, alkylthio, arylthio, heteroarylthio, cyano, carboxyl, alkoxycarbonyl, wherein the alkyl portion contains 1 to 15 carbon atoms, aryloxycarbonyl, wherein the aryl portion contains 6 to 20 carbon atoms, or heteroaryloxycarbonyl radicals, wherein the heteroaryl portion contains 3 to 15 carbon atoms;
G1 represents a hydrogen or a hydroxyl protecting group;
and
Y is oxygen.

4 more elements

A β-lactam of the formula I:

in which:
R2′ represents RO—, RS—, or RR′N— in which R represents a straight-chain or branched alkyl, alkenyl, or alkynyl radical, a cycloalkyl, cycloalkenyl, aryl, or unsaturated or saturated heterocyclic radical containing 3 to 15 carbon atoms, wherein said heterocyclic radical contains at least one oxygen, nitrogen, or sulfur atom, R′ is hydrogen or R as defined above, or R and R′ are together an alkylene, alkenylene, or alkynylene of 2 to 10 carbons;
R3′ represents a straight-chain or branched alkyl, alkenyl, or alkynyl radical, or a cycloalkyl, cycloalkenyl, or aryl radical;
wherein R and R3′ are unsubstituted or substituted with one or more halogen, hydroxyl, alkoxy, aryloxy, heteroaryloxy, amino, alkylamino, dialkylamino, mercapto, alkylthio, arylthio, heteroarylthio, cyano, carboxyl, alkoxycarbonyl, wherein the alkyl portion contains 1 to 15 carbon atoms, aryloxycarbonyl, wherein the aryl portion contains 6 to 20 carbon atoms, or heteroaryloxycarbonyl radicals, wherein the heteroaryl portion contains 3 to 15 carbon atoms;
G1 represents a hydrogen or a hydroxyl protecting group;
and
Y is sulfur.

4 more elements

Dependencies are inferred from the claim text.

Process for the preparation of taxane derivatives and β-lactam intermediates therefor

Life of this patent

Process for the preparation of taxane derivatives and β-lactam intermediates therefor

Life of this patent

Abstract

Claims13