US4341706A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for the preparation of carbapenem antibiotics
Assignee: Merck and Co Inc
•
Filing: 1980-10-10
•
Granted: 1982-07-27
•
Expires: 2000-10-10
Abstract
Abstract Disclosed is a process for the synthesis of carbapenem antibiotics I and their pharmaceutically acceptable salts and esters from 1: <IMAGE> <IMAGE> wherein: R7, R6, R1, R2 and R8 are selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, spirocycloalkyl, cycloalkylalkyl, alkylcycloalkyl, aryl, aralkyl, aralkenyl, aralkynyl, heteroalkyl, heteroaralkyl, heterocyclyl and heterocyclyalkyl.
Inventors
- 👤 Burton G. Christensen
- 👤 David H. Shih
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 09:49
CPC Classifications
C; C07; C07C; C07C17/00; C07C17/26; C07C17/272; C07C17/275; C07D; C07D205/00; C07D205/02; C07D205/06; C07D205/08; C07D477/00; C07D477/02; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/10; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/568
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
253 words
A process for preparing a compound having the structure: ##STR105## and the pharmaceutically acceptable salts thereof; wherein R 1 , R 2 , R 6 , R 7 and R 8 are independently selected from the group consisting of hydrogen (R 1 and R 2 are not both 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; spirocycloalkyl having 3-6 carbon atoms; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the alkyl chain has 1-6 carbon atoms; thiophenyl, imidazolyl, tetrazolyl, furyl; thiophenylalkyl, imidazolylalkyl, tetrazolylalkyl and furylalkyl wherein the alkyl moiety contains from 1-10 carbon atoms, and wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: amino, mono-, di-, and trialkylamino, hydroxyl, alkoxyl, mercapto, alkylthio, phenylthio, sulfamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, iodo, cyano and carboxy wherein the alkyl moieties of the above-recited substituents have 1-6 carbon atoms; comprising the steps of treating; ##STR106## with HSR 8 to yield: ##STR107## followed by treating with iodobenzenedichloride to yield: ##STR108## followed by dehydrochlorination in the presence of a strong base at 0° to 6° C., reduction with a reducing agent at -20° to 40° C. and deblocking by hydrogenation in the presence of a catalyst at 0° to 60° C. wherein R° is selected from the group consisting of hydrogen, an alkali metal, nitrobenzyl, tertiary butylbenzyl, trichloroacetoxymethyl, and triloweralkylkammonium.
Claim 2
Dependent Claim
253 words
A process for preparing a compound having the structure: ##STR105## and the pharmaceutically acceptable salts thereof; wherein R 1 , R 2 , R 6 , R 7 and R 8 are independently selected from the group consisting of hydrogen (R 1 and R 2 are not both 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; spirocycloalkyl having 3-6 carbon atoms; phenyl; aralkyl, aralkenyl, and aralkynyl wherein the aryl moiety is phenyl and the alkyl chain has 1-6 carbon atoms; thiophenyl, imidazolyl, tetrazolyl, furyl; thiophenylalkyl, imidazolylalkyl, tetrazolylalkyl and furylalkyl wherein the alkyl moiety contains from 1-10 carbon atoms, and wherein the substituent or substituents relative to the above-named radicals are selected from the group consisting of: amino, mono-, di-, and trialkylamino, hydroxyl, alkoxyl, mercapto, alkylthio, phenylthio, sulfamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, iodo, cyano and carboxy wherein the alkyl moieties of the above-recited substituents have 1-6 carbon atoms; comprising the steps of treating; ##STR106## with HSR 8 to yield: ##STR107## followed by treating with iodobenzenedichloride to yield: ##STR108## followed by dehydrochlorination in the presence of a strong base at 0° to 6° C., reduction with a reducing agent at -20° to 40° C. and deblocking by hydrogenation in the presence of a catalyst at 0° to 60° C. wherein R° is selected from the group consisting of hydrogen, an alkali metal, nitrobenzyl, tertiary butylbenzyl, trichloroacetoxymethyl, and triloweralkylkammonium.
Claim 3
Dependent Claim
46 words
A process for preparing a compound according to claim 1 wherein R 1 and R 2 are selected from hydrogen, alkyl, cycloalkyl, spirocycloalkyl, benzyl or phenyl; and R 6 is H or methyl and R 7 is alkyl, phenyl, aralkyl or hydroxyl-substituted alkyl, phenyl or aralkyl.
Claim 4
Dependent Claim
35 words
A process for preparing a compound according to claim 2 wherein R 1 and R 2 are selected from hydrogen, spirocyclopropyl, methyl, ethyl, isopropyl, t-butyl or phenyl and R 7 is 1-hydroxyethyl, methyl or hydroxymethyl.
Claim 5
Dependent Claim
17 words
A process according to claim 1 wherein R 8 is selected from the group consisting of: ##STR109##
Claim 6
Dependent Claim
50 words
A process for preparing a compound according to claim 4 wherein R 6 is H or methyl; R 7 is selected from: ##STR110## and R 1 and R 2 are selected from hydrogen, spirocyclopropyl; phenyl; cycloalkyl having 3-6 carbon atoms; alkyl having 1-6 carbon atoms; cyclopropylalkyl having 4-9 carbon atoms.
Claim 7
Dependent Claim
11 words
A process according to claim 5 wherein R 1 is hydrogen.
Claim 8
Dependent Claim
17 words
A process for preparing a compound according to claim 1 selected from the group consisting of: ##STR111##
Claim 9
Dependent Claim
27 words
A process for preparing a compound according to claim 7 wherein the aminoethylthio side chain ##STR112## is replaced by a member of the group consisting of: ##STR113##
Claim 10
Dependent Claim
15 words
A process for preparing a compound according to claim 1 wherein R 1 is hydrogen.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-07-26 | 1986-01-25 | 1986-07-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-07-26 | 1990-01-25 | 1990-07-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-07-26 | 1994-01-25 | 1994-07-27 | $7700.00 | Window Closed / Lapsed |