Practical synthesis of 2-pyridone core: Ethyl 8-chloro-1-cyclopropyl-7- fluoro-9-methyl-4-oxo-4H-quinolizinone-3-carboxylate

Heterocycles

Volumn 51, Issue 6, 1999, Pages 1345-1353

  Li, Qun ^a   Sowin, Thomas ^a   Claiborne, Akiyo ^a   Lijewski, Linda ^a   Zhang, Xiaolin ^a   Raye, Kathleen ^a   Mazdiyasni, Hormoz ^a   Arnold, William ^a   Melcher, Laura M ^a   Wang, Weibo ^a   Hasvold, Lisa ^a   Fung, Anthony ^a   Chu, Daniel T W ^a   Plattner, J J ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PYRIDONE DERIVATIVE; 8 (3 AMINO 1 PYRROLIDINYL) 1 CYCLOPROPYL 7 FLUORO 9 METHYL 4 OXO 3 QUINOLIZINECARBOXYLIC ACID; 8 CHLORO 1 CYCLOPROPYL 7 FLUORO 9 METHYL 4 OXO 4H QUINOLIZINONE 3 CARBOXYLIC ACID ETHYL ESTER; ANTIINFECTIVE AGENT; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

EID: 0033150538     PISSN: 03855414     EISSN: None     Source Type: Journal    
DOI: 10.3987/COM-99-8500     Document Type: Article

References (16)

1. Q. Li, D. T. Chu, A. Claiborne, C. S. Cooper, C. M. Lee, K. Raye, K. B. Berst, P. Donner, W. Wang, L. Hasvold, A. Fung, Z. Ma, M. Tufano, R. Flamm, L. L. Shen, J. Baranowski, A. Nilius, J. Alder, J. Meulbroek, K. Marsh, D. Crowell, Y. Hui, L. Seif, L. M. Melcher, R. Henry, S. Spanton, R. Faghih, L. L. Klein, S. K. Tanaka, and J. J. Plattner, J. Med. Chem., 1996, 39, 3070, and references therein.
2. For other 2-pyridone related papers, see: (a) Q. Li, W. Wang, K. B. Berst, A. Claiborne, L. Hasvold, K. Raye, M. Tufano, A. Nilius, L. L. Shen, R. Flamm, J. Alder, K. Marsh, D. Crowell, D. T. W. Chu, and J. J. Plattner, Bioorg. Med. Chem. Lett., 1998, 8, 1953.
3. (b) Z. Ma, D. T. W. Chu, Q. Li, L. L. Shen, A. Fung, C. S. Cooper, W. Wang, S. Wang, R. K. Flamm, A. Nilius, J. D. Alder, S. K. Tanaka, Y. Or, and J. J. Plattner, 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1997, Abstract F169.
4. (c) T. Park, K. Nam, Y. Ha, Y. Choi, Y. Choi, J. Kong, and Y. Kim, 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1997, Abstract 173.
5. (d) L. L. Klein, D. A. DeGoey, S. A. Thomas, C. M. Yeung, C. L. Leone, D. J. Grampovnik, D. T. Chu, and P. A. Lartey, Bioorg. Med. Chem. Lett., 1997, 7, 1167.
6. (e) R. K. Flamm, C. Vojtko, D. T. Chu, D. Q. Li, J. Beyer, D. Hensey, N. Ramer, J. J. Clement, and S. K. Tanaka, Antimicrob. Agents Chemother, 1995, 39, 964.
7. (f) G. M. Eliopoulos, C. B. Wennersten, G. Cole, D. Chu, D. Pizzuti, and R. C. Moellering, Jr., Antimicrob. Agents Chemother, 1995, 39, 850.
8. (g) J. Alder, J. Clement, J. Meulbroek, N. Shipkowitz, M. Mitten, K. Jarvis, A. Oleksijew, T. Hutch, Sr., L. Paige, R. Flamm, D. Chu, and K. Tanaka, Antimicrob. Agents Chemother, 1995, 39, 971.
9. (h) R. A. Fromtling, Drugs Fut., 1995, 20, 1103.
10. R. D. Chambers, J. Hutchinson, and W. K. R., Muscrave, J. Chem, Soc., 1964, 3573. The 70% pure 3 was available from Aldrich. The pure 3 is now available from both Fluorochem and Aldrich.
11. Repeating the same reaction starting with the 99% pure 3-chlorotetrafluoro-pyridine (3) gave 4-tertbutoxypyridine 4 in 75% yield on a kilogram scale.
12. R. D. Chambers, D. Close, W. K. R. Musgrave, J. S. Waterhouse, and D. L. H. Williams, J. Chem. Soc., Perkin Trans II, 1977, 1774.
13. R. D. Chambers, J. Hutchinson and W. K. R. Musgrave, J. Chem. Soc., 1964, 5634.
14. Separation of 4 and 5 is not necessary. However, when pure 4 was used, the overall yield from 4 to 7 increased to 67%.
15. Recently, Park and his colleagues claimed at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy that they were able to reduce 9 directly to the aldehyde using DIBAL as a reducing agent. Our reduction attempts using DIBAL under several different conditions were unsuccessful. See ref. 2c.
16. Dowtherm A is a mixture of biphenyl and diphenyl ether (23:77).