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US4160085A Expired / Lapsed US ⏱️ 0.0 years remaining

Cyclization to form cephem ring and intermediates therefor

Assignee: Eli Lilly and Co
•
Filing: 1977-12-01
•
Granted: 1979-07-03
•
Expires: 1997-12-01
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Abstract

Abstract Intermediates represented by the following formulas are useful for synthesizing 3-hydroxy-3-cephem compounds ##STR1## wherein A and B each is a hydrogen or amino substituent; R is a hydrogen or thiol substituent; Hal is a halogen; X is a hydroxy or carboxy protecting group; the broken line between A and R shows that when R and B are hydrogens, and A is a carboxylic acyl, the substituents can be combined to form an azetidinothiazoline bicyclic ring; and the enamine derivatives thereof. One embodiment provides for cyclizing a compound of the formula: ##STR2## wherein A, B, X and Hal are as defined above, which comprises treating the said compound with an acid, base, or solvent if required in the presence of a catalyzer to give a compound represented by following formula ##STR3## In a further embodiment a compound represented by the following formula ##STR4## wherein A, B, R and X are as defined above, is prepared by a process which comprises treating an enamine of a compound represented by following formula ##STR5## wherein A, B, R, X, Hal and broken line are as defined above, with a disubstituted amino containing from 2 to 20 carbon atoms, with the action of an aqueous acid.

Inventors

  • 👤 Teruji Tsuji
  • 👤 Yoshio Hamashima
  • 👤 Mitsuru Yoshioka
  • 👤 Masayuki Narisada
  • 👤 Hiroshi Tanida
  • 👤 Taichiro Komeno
  • 👤 Wataru Nagata

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-30 17:56
CPC Classifications
C; C07; C07D; C07D205/00; C07D205/02; C07D205/06; C07D205/08; C07D205/09; C07D205/095; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55

Claims Analysis

Total Claims: 6
Claim 1
Independent Claim 189 words
A process for cyclizing a compound represented by the formula ##STR157## wherein R' represents a member selected from the group consisting of (1) hydrogen, (2) C 1 to C 4 alkyl, (3) phenyl, (4) α-chlorobenzyl, (5) ArCQQ, (6) Ar-G-CQQ wherein Q represents hydrogen or methyl, G represents oxygen or sulfur and Ar represents (a) phenyl, (b) dihydrophenyl, (c) monocyclic heterocyclic aromatic containing from 1 to 4 hereto atoms selected from the group of nitrogen, oxygen and sulfur or (d) one of said groups (a) to (c) substituted by an inert group selected from the group of alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, chlorine, bromine, iodine, fluorine, trifluoromethyl hydroxy, cyano, aminomethyl, amino and nitro, or ##STR158## represents phthalimido, COX represents carboxy or protected carboxy, and Hal represents a halogen atom, which comprises the step of treating the said compound with a member of the group consisting of acid, base, solvent and a solvent together with a catalyzer selected from the group of a neutral or basic silica gel, alumina, diatomaceous earth and fluorisil to give a compound represented by the formula ##STR159##
Claim 2
Dependent Claim 189 words
A process for cyclizing a compound represented by the formula ##STR157## wherein R' represents a member selected from the group consisting of (1) hydrogen, (2) C 1 to C 4 alkyl, (3) phenyl, (4) α-chlorobenzyl, (5) ArCQQ, (6) Ar-G-CQQ wherein Q represents hydrogen or methyl, G represents oxygen or sulfur and Ar represents (a) phenyl, (b) dihydrophenyl, (c) monocyclic heterocyclic aromatic containing from 1 to 4 hereto atoms selected from the group of nitrogen, oxygen and sulfur or (d) one of said groups (a) to (c) substituted by an inert group selected from the group of alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, chlorine, bromine, iodine, fluorine, trifluoromethyl hydroxy, cyano, aminomethyl, amino and nitro, or ##STR158## represents phthalimido, COX represents carboxy or protected carboxy, and Hal represents a halogen atom, which comprises the step of treating the said compound with a member of the group consisting of acid, base, solvent and a solvent together with a catalyzer selected from the group of a neutral or basic silica gel, alumina, diatomaceous earth and fluorisil to give a compound represented by the formula ##STR159##
Claim 3
Dependent Claim 31 words
A process according to claim 1 wherein the acid is a mineral acid, sulfonic acid, phosphonic acid, or carboxylic acid, or their salts with a weak base, or their acidic salts.
Claim 4
Dependent Claim 13 words
A process according to claim 1 wherein the base is a weak base.
Claim 5
Dependent Claim 20 words
A process according to claim 1 wherein the solvent is an amide, alcohol, or water solvents as the cyclization reagent.
Claim 6
Dependent Claim 77 words
A process for preparing a compound of the following formula: ##STR160## wherein R' and COX are as defined in claim 1 which comprises the step of treating a compound of the following formula: ##STR161## wherein R' and COX are as defined above, Hal is halogen, and Y is morpholino-4-yl, C 4-8 alkyleneamino, C 2-6 dialkylamino or C 14-20 diaralkylamino, to the action of an aqueous protonic acid in a solvent selected from alcoholic, etheric and halohydrocarbon solvent.

References Cited (Backward Citations)

US4079181A Cited
US4066641A Cited
US4008230A Cited
US4058521A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1982-07-02 1983-01-01 1983-07-03 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1986-07-02 1987-01-01 1987-07-03 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1990-07-02 1991-01-01 1991-07-03 $7700.00 Window Closed / Lapsed

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