EP0365863A2
Expired / Lapsed
EP
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Novel quinolyloxazole-2-ones useful as proteinkinase C inhibitors
Assignee: Aventis Pharmaceuticals Inc
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Filing: 1989-09-28
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Granted: —
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Expires: 2009-09-28
Abstract
Abstract This invention relates to novel quinolyloxazole-2-ones which are useful as protein kinase C inhibitors, effective in the treatment of hypertension and asthma. This invention also includes a novel procedure for producing an intermediate ketone compound involving the reaction of a bromo-quinoline compound with butyl lithium and further reacting the lithiated compound with N-methyl-N-methoxyalkanamide.
Inventors
- 👤 Winton Dr. Jones
- 👤 George P. Claxton
- 👤 Phillip J. Robinson
- 👤 Richard C. Dage
- 👤 Hsien C. Cheng
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 03:31
CPC Classifications
C; C07; C07D; C07D413/00; C07D413/02; C07D413/04; A; A61; A61P; A61P11/00; A61P11/08; A61P43/00; A61P9/00; A61P9/08; A61P9/12
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
198 words
A process for preparing a compound of the formula (I) wherein R and R¹ are each independently selected from the group consisting of hydrogen, C₁-C₆ alkyl, and C₁-C₃ alkylphenyl wherein the phenyl ring is optionally substituted with one, two or three of the substituents selected from the group consisting of fluorine, chlorine, bromine, C₁-C₄ alkyl, and C₁-C₄ alkoxy; and R² is a 2-, 3-, or 4-quinolyl group, optionally substituted with one, two or three of the substituents selected from the group consisting of fluorine, chlorine, bromine, C₁-C₄ alkyl, C₁-C₄ alkoxy, nitro and trifluoromethyl, or R² is a 5-, 6-, 7-, or 8-quinolyl group; which comprises reacting an optionally substituted 2-, 3-, 4-, or a 5-, 6-, 7-, or 8-bromoquinoline with butyl lithium in tetrehydrofuran or ether at a temperature of from -70 °C to 0 °C, and then further reacting the lithiated compound with a compound of the formula to form an alkanone of the formula (IV) or (IX) then brominating the alkanone and subsequently treating the compound with triethylamine in dimethylformamide in the presence of potassium cyanate, and then optionally reacting the resulting product with sodium hydride and an appropriate alkyl iodide or phenylalkyl iodide in tetrahydrofuran.
Claim 2
Dependent Claim
198 words
A process for preparing a compound of the formula (I) wherein R and R¹ are each independently selected from the group consisting of hydrogen, C₁-C₆ alkyl, and C₁-C₃ alkylphenyl wherein the phenyl ring is optionally substituted with one, two or three of the substituents selected from the group consisting of fluorine, chlorine, bromine, C₁-C₄ alkyl, and C₁-C₄ alkoxy; and R² is a 2-, 3-, or 4-quinolyl group, optionally substituted with one, two or three of the substituents selected from the group consisting of fluorine, chlorine, bromine, C₁-C₄ alkyl, C₁-C₄ alkoxy, nitro and trifluoromethyl, or R² is a 5-, 6-, 7-, or 8-quinolyl group; which comprises reacting an optionally substituted 2-, 3-, 4-, or a 5-, 6-, 7-, or 8-bromoquinoline with butyl lithium in tetrehydrofuran or ether at a temperature of from -70 °C to 0 °C, and then further reacting the lithiated compound with a compound of the formula to form an alkanone of the formula (IV) or (IX) then brominating the alkanone and subsequently treating the compound with triethylamine in dimethylformamide in the presence of potassium cyanate, and then optionally reacting the resulting product with sodium hydride and an appropriate alkyl iodide or phenylalkyl iodide in tetrahydrofuran.
Claim 3
Dependent Claim
20 words
A process according to claim 1 for preparing a compound wherein R² is a 5-, 6-, 7-, or 8-quinolyl group.
Claim 4
Dependent Claim
21 words
A process according to claim 1 for preparing a compound wherein R² is an optionally substituted 2-, 3-, or 4-quinolyl group.
Claim 5
Dependent Claim
27 words
A process according to claim 3 for preparing a compound wherein R and R¹ are each independently selected from the group consisting of hydrogen or C₁-C₆ alkyl.
Claim 6
Dependent Claim
19 words
A process according to claim 4 for preparing a compound wherein R is C₁-C₆ alkyl and R¹ is hydrogen.
Claim 7
Dependent Claim
20 words
A process according to claim 3 for preparing a compound wherein R² is an unsubstituted 2-, 3-, or 4-quinolyl group.
Claim 8
Dependent Claim
21 words
A process according to claim 6 for preparing a compound wherein R₂ is 4-quinolinyl, R is propyl, and R¹ is hydrogen.
Claim 9
Dependent Claim
22 words
A process according to any of claims 1 to 7 wherein the bromoquinoline is reacted with butyl lithium in tetrahydrofuran or ether.
Claim 10
Dependent Claim
26 words
A process according to any of claims 1 to 7 wherein the bromoquinoline/butyl lithium reaction is effectuated at a temperature of -60 °C to -55 °C.
Claim 11
Dependent Claim
26 words
A process according to any of claims 1 to 7 wherein the lithiated compound is further reacted at a temperature of -50 °C to 0 °C.
Claim 12
Dependent Claim
52 words
A process according to any of claims 1 to 7 wherein the bromoquinoline is reacted with butyl lithium in tetrahydrofuran, and the bromoquinoline/butyl lithium reaction is effectuated at a temperature of -60 °C to -55 °C, and the lithiated compound is further reacted at a temperature of -50 °C to 0 °C.
References Cited (Backward Citations)
No citation records indexed.
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