Practical asymmetric synthesis of a selective endothelin A receptor (ETA) antagonist

Organic Letters

Volumn 3, Issue 21, 2001, Pages 3357-3360

  Song, Zhiguo J ^a   Zhao, Matthew ^a   Frey, Lisa ^a   Li, Jing ^a   Tan, Lushi ^a   Chen, Cheng Y ^a   Tschaen, David M ^a   Tillyer, Richard ^a   Grabowski, Edward J J ^a   Volante, Ralph ^a   Reider, Paul J ^a   Kato, Yoshiaki ^b   Okada, Shigemitsu ^b   Nemoto, Takayuki ^b   Sato, Hiroki ^b   Akao, Atsushi ^b   Mase, Toshiaki ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b BANYU PHARMACEUTICAL CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIHYPERTENSIVE AGENT; BENZOFURAN DERIVATIVE; ENDOTHELIN A RECEPTOR; ENDOTHELIN RECEPTOR; PYRIDINE DERIVATIVE;

ARTICLE; DRUG ANTAGONISM; SYNTHESIS;

ANTIHYPERTENSIVE AGENTS; BENZOFURANS; PYRIDINES; RECEPTOR, ENDOTHELIN A; RECEPTORS, ENDOTHELIN;

EID: 18044403182     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol016601s     Document Type: Article

References (15)

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2. (b) Ishikawa, K.; Nagase, T.; Mase, T., Hayama, T.; Ihara, M.; Nishikibe, M.; Yano, M. PCT Int. Appi. WO 9505374, 1995.
3. Clark, W. M. Curr. Opin. Drug Discovery Dev. 1999, 2, 565.
4. (a) Song, Z. J.; Zhao, M.; Desmond, R.; Devine, P.; Tschaen, D. M.; Tillyer, R.; Frey, L.; Heid, R.; Xu, F.; Foster, B.; Li, J.; Reamer, R.; Volante, R.; Grabowski, E. J.; Dolling, U.-H.; Reider, P. J.; Okada, S.; Kato, Y.; Mano, E. J. Org. Chem. 1999, 64, 9658-9667.
5. (b). Devine, Paul N.; Desmond, R.; Frey, L.; F.; Heid, R. M.; Song, Z.; Tillyer, R. D.; Tschaen, D. M.; Zhao, M.; Kato, Y.; Mano, E.; Okada, S.; Kato, S.; Mase, T. Yuki Gosei Kagaku Kyokaishi 1999, 57, 1016-1025
6. (a) Frey, L. F.; Tillyer, R. D.; Caille, A.-S.; Tschaen, D. D.; Dolling, U.-H.; Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1998, 63, 3120.
7. (b) Alexakis, A.; Sedrani, R.; Mangeney, P.; Normant, J. F. Tetrahedron Lett. 1988, 29, 411.
8. (a) Paper from Banyu Medicinal Chemistry, manuscript in preparation.
9. 3 and 0.3 equiv of water were added to get complete conversion.
10. (c) Bradsher, C. K.; Reames, D. C. J. Org. Chem. 1981, 46, 1384.
11. 3, ppm) 161.1, 126.2, 125.8, 123.3, 120.8, 112.9, 71.9, 29.3; HPLC 95% pure by area.
12. 1H NMR (250 MHz, CDC13, ppm) 1.21 (d, J = 6.7 Hz, 6 H), 4.52 (s, 2H), 5.11 (hep, J = 6.7 Hz, 1H), 6.18 (d, J = 8.4 Hz, 1H), 6.0.68 (d, H=7.4 Hz, 1H), 7.14 (dd, J = 8.4, 7.4 Hz, 1H), 7.2-7.4 (m, 5H).
13. 3, ppm) 1.25 (d, 6H, J = 6.7 Hz), 1.54 (s, 9H), 4.68 (s, 2H), 5.35 (br, m, 1H), 6.41 (d, J = 10 Hz, 1H), 6.89 (d, J = 15 Hz, 1H), 7.15-7.36 (m, 5H), 7.83 (d, J = 10 Hz, 1H), 8.29 (d, J = 15 Hz, 1H), 10.20 (s 1H).
14. 13C NMR and elemental analysis results were obtained.
15. 3COH in the presence of t-BuOK.