Process for the preparation of 1-carbapenems and intermediates via silyl-substituted dithioacetals

Claim 2

A compound selected from the group consisting of: wherein R 1 ' is hydrogen or a readily removable protecting group; R a and R b are independently selected from: alkyl having 1-6 carbon atoms, phenyl, benzyl, methoxybenzyl, trityl, and -(CH 2 ) 3 - (joinder of R a and R b ); R c is alkyl having 1-6 carbon atoms, and phenyl; and wherein R 6 and R 7 are independently selected from the group consisting of: hydrogen; substituted and unsubstituted: alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: chloro, bromo, fluoro, R 1 , and wherein, relative to the above listed substituents on R 6 , and R 7 , the groups R l and R 2 are independently selected from: hydrogen, alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; and wherein the hetero atom or atoms in the above-named heterocyclic moieties are selected from the group consisting of 1-4 oxygen, nitrogen or sulphur atoms and wherein the alkyl moieties associated with said heterocyclic moieties have 1-6 carbon atoms; R and R 7 are not both hydrogen at the same time; when R 6 / R 7 is hydrogen, then R 7 /R 6 is not

Claim 3

A compound according to Claim 1 wherein R 1 ' is hydrogen or a triorganosilyl group.

Claim 4

A compound according to Claim 2 wherein R 1 ' is hydrogen or a trialkylsilyl group wherein each alkyl moiety has from 1-6 carbon atoms; R c is alkyl having 1-3 carbon atoms, phenyl; and R a and R b are: -(CH2)3-, or alkyl having 1-3 carbon atoms each.

Claim 5

A compound according to Claims 1, 2 or 3 wherein R 6 and R 7 are independently selected from the group consisting of: hydrogen; substituted and unsubstituted: alkyl, alkenyl and alkynyl having from 1-10 carbon atoms, cycloalkyl, cycloalkylalkyl and alkylcycloalkyl, having 3-6 carbonatoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic protion has 1-6 carbon atoms; wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: chloro, bromo, fluoro, and wherein, relative to the above listed substituents on R 6 , and R 7 , the groups R 1 and R 2 are independently selected from: hydrogen, alkyl, alkenyl and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties, phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms.

Claim 6

A compound according to Claims 1, 2, 3 or 4 wherein R 7 is hydrogen or methyl.

Claim 7

A compound according to Claim 5 wherein R 6 is selected from the group consisting of: substituted and unsubstituted: alkyl, alkenyl and cycloalkylalkyl wherein the substituent or substituents are selected from hydroxyl, alkoxyl having from 1-6 carbon atoms, phenoxy, amino, and carboxy.

Claim 8

A compound according to Claims 5 or 6 wherein R6is selected from the group consisting of alkyl, cycloalkylalkyl, alkyl substituted by one or more hydroxyl groups, or cycloalkylalkyl substituted by one or more hydroxyl groups.

Claim 9

A compound according to Claims 5, 6 or 7 wherein R 7 is hydrogen.

Claim 10

A process for preparing a compound according to Claims 1, 2, 3, 4, 5, 6, 7 or 8 having the structure: which comprises the steps of treating: with: wherein M is a metal cation to yield: followed by treating in the presence of base with an alkylating or acylating agent calculated to establish R and R 7 .

Claim 11

A process for preparing a compound according to Claims 1, 2, 3, 4, 5, 6, 7 or 8 having the structure: comprising treating a compound according to Claim 9 with a Lewis acid.

Claim 12

A process for preparing: comprising the step of treating a compound of Claim 10 with an oxidizing agent.

Claim 13

A compound according to Claim 1 wherein R 7 is hydrogen and R 6 is selected from the group consisting of:

Claim 14

A process for preparing and the pharmaceutically acceptable salt, ester and amide derivatives thereof; wherein: R 6 , R 7 and R 8 are independently selected from the group consisting of: hydrogen; substituted and unsubstituted: alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: chloro, bromo, fluoro, and wherein, relative to the above listed substituents on R 6 , and R 7 , the groups R 1 and R 2 are independently selected from: hydrogen, alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; and wherein the hetero atom or atoms in the above-named heterocyclic moieties are selected from the group consisting of 1-4 oxygen, nitrogen or sulphur atoms and wherein the alkyl moieties associated with said heterocyclic moieties have 1-6 carbon atoms; when -R 6 /R 7 is hydrogen, then R 7/R 6 is not when R 8 is CH 2 CH 2 NH 2 ; which process comprises the steps of oxidizing: to form: wherein R 1 ' is hydrogen or a protecting group; and R c is independently selected from alkyl having 1-6 carbon atoms and phenyl; followed by treating with 1,1'-carbonyldimidazole followed by (R 2' O 2 CCH 2 CO 2 ) 2 Mg to yield: wherein R 2' is a protecting group or a pharmaceutically acceptable ester moiety; followed by diazotizing, cyclizing, activating and reacting with HSR 8 .

Claim 15

A process for preparing and the pharmaceutically acceptable salt, ester and amide derivatives thereof; wherein: R 6 , R 7 and R 8 are independently selected from the group consisting of: hydrogen; substituted and unsubstituted: alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: chloro, bromo, fluoro, and wherein, relative to the above listed substituents on R 6 , and R 7 , the groups R 1 and R 2 are independently selected from: hydrogen, alkyl, alkenyl, and alkynyl, having from 1-10 carbon atoms; cycloalkyl, cycloalkylalkyl, and alkylcycloalkyl, having 3-6 carbon atoms in the cycloalkyl ring and 1-6 carbon atoms in the alkyl moieties; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the aliphatic portion has 1-6 carbon atoms; heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl; and wherein the hetero atom or atoms in the above-named heterocyclic moieties are selected from the group consisting of 1-4 oxygen, nitrogen or sulphur atoms and wherein the alkyl moieties associated with said heterocyclic moieties have 1-6 carbon atoms; when -R 6 /R 7 is hydrogen, then R 7/R 6 is not when R 8 is CH 2 CH 2 NH 2 ; which process comprises the steps of oxidizing: to form: wherein R 1 ' is hydrogen or a protecting group; and R c is independently selected from alkyl having 1-6 carbon atoms and phenyl; followed by treating with 1,1'-carbonyldimidazole followed by (R 2' O 2 CCH 2 CO 2 ) 2 Mg to yield: wherein R 2' is a protecting group or a pharmaceutically acceptable ester moiety; followed by diazotizing, cyclizing, activating and reacting with HSR 8 .