Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters

Tetrahedron Letters

Volumn 49, Issue 5, 2008, Pages 811-815

  Murphy, Douglas E ^a   Dragovich, Peter S ^a   Ayida, Benjamin K ^a   Bertolini, Thomas M ^a   Li, Lian Sheng ^a   Ruebsam, Frank ^a   Stankovic, Nebojsa S ^a   Sun, Zhongxiang ^a   Zhao, Jingjing ^a   Zhou, Yuefen ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Hydrazono ester; Keto ester; Dieckmann cyclization; Pyridazinone; Selective alkylation

Indexed keywords

6 SUBSITUTED 5 HYDROXY 3 OXO 2,3 DIHYDRO PYRIDAZINE 4 CARBOXYLIC ACID ETHYL ESTER DERIVATIVE; ALPHA HYDRAZONO ESTER; ALPHA KETO ESTER; ESTER DERIVATIVE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; DIECKMANN REACTION; SUBSTITUTION REACTION; SYNTHESIS;

EID: 37649021331     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2007.11.187     Document Type: Article

References (21)

1. Corsano S., Vezza R., Scapicchi R., Foresi S., Strappaghetti G., Nenci G.G., and Gresele P. Eur. J. Med. Chem. 30 (1995) 627
2. Betti L., Zanelli M., Giannaccini G., Manetti F., Schenone S., and Strappaghetti G. Bioorg. Med. Chem. 14 (2006) 2828 and references cited therein
3. Yamada T., Nobuhara Y., Shimamura H., Tsukamoto Y., Yoshihara K., Yamaguchi A., and Ohki M. J. Med. Chem. 26 (1983) 373
4. Li L.-S., Zhou Y., Zhao J., Dragovich P.S., Stankovic N., Bertolini T.M., Murphy D.E., Sun Z., Tran C.V., Ayida B.K., Ruebsam F., and Webber S.E. Synthesis 21 (2007) 3301
5. Yamada T., and Ohki M. Synthesis 8 (1981) 631
6. King J., and McMillan F. J. Am. Chem. Soc. 74 (1952) 3222
7. McMillan F., Kun K., McMillan C., Schwartz B., and King J. J. Am. Chem. Soc. 78 (1956) 407
8. Nitta Y., Yoneda F., Ohtaka T., and Kato T. Chem. Pharm. Bull. 12 (1964) 69
9. Holava H.M., and Partyka R.A. J. Med. Chem. 14 (1971) 262
10. The required α-keto-ester was obtained in 51% yield following a modified procedure from. Dondoni A., Fantin G., Fogagnolo M., Medici A., and Pedrini P. J. Org. Chem. 53 (1988) 1748 A neat mixture of 5-trimethylsilanyl-thiazole (1 equiv) and chloro-oxo-acetic acid ethyl ester (2 equiv) was heated at 80 °C for 1.75 h. After cooling to 25 °C, flash column chromatography (10-25% EtOAc/hexanes) afforded the α-keto-ester
11. 2O. Concentration in vacuo followed by flash column chromatography afforded the desired α-keto-ester
12. The required α-keto-ester was obtained in 53% yield by following the procedure described by. Babudri F., Fiandanese V., Marchese G., and Punzi A. Tetrahedron 52 (1996) 13513 (replacing chloro-oxo-acetic acid methyl ester with chloro-oxo-acetic acid ethyl ester)
13. The required α-keto-ester was obtained by following the procedure described in. Graham D.W., Ashton W.T., Barash L., Brown J.E., Brown R.D., Canning L.F., Chen A., Springer J., and Rogers E.F. J. Med. Chem. 30 (1987) 1074
14. No attempt was made to assign the hydrazone products as either the E or Z-isomers.
15. Dragovich P.S., Bertolini T.M., Ayida B.K., Li L.-S., Murphy D.E., Ruebsam F., Sun Z., and Zhou Y. Tetrahedron 63 (2007) 1154
16. 2. Concentration in vacuo afforded the desired tosylate.
17. 14 However, it was necessary to heat the reaction mixture to 45 °C for 16 h.
18. Wolniewicz A., and Dmowski W. J. Fluorine Chem. 109 (2001) 95
19. 5S: C, 49.99; H, 5.16; N, 8.97. Found: C, 49.83; H, 5.38; N, 9.01.
20. 4S: C, 49.62; H, 3.79; N, 10.52. Found: C, 49.48; H, 4.09; N, 10.67.
21. 4S: C, 57.12; H, 5.99; N, 8.33. Found: C, 57.13; H, 6.38; N, 8.49.