Remarkable three-step-one-pot solution phase preparation of novel imidazolines utilizing a UDC (Ugi/de-Boc/cyclize) strategy

Tetrahedron Letters

Volumn 40, Issue 45, 1999, Pages 7925-7928

  Hulme, Christopher ^a   Ma, Liang ^a   Romano, Joseph ^a   Morrissette, Matthew ^a,b  

^a Department of New Leads Discovery   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOALDEHYDE; IMIDAZOLINE DERIVATIVE;

ARTICLE; CYCLIZATION; DIASTEREOISOMER; DRUG SYNTHESIS; POLYMERIZATION;

EID: 0033527709     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01580-4     Document Type: Article

References (29)

1. For two reviews, see: (a) Storer, R. Drug Discovery Today, 1996, 1, 248.
2. (b) Balkenhohl, F.; Bussche-Hünnefeld, C.; Lansky, A.; Zechel, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2288.
3. For two reviews, see: (a) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527.
4. (b) Terrett, N. K.; Gardner, M.; Gordon, D. W.; Kobylecki, R. J.; Steele, J. Tetrahedron 1995, 51, 8135.
5. (a) Hulme, C.; Morrissette, M. M.; Volz, F. A.; Burns, C. J. Tetrahedron Lett. 1998, 39, 113.
6. (b) Bienayme, H.; Bouzid, K.; Tetrahedron Lett. 1998, 39, 2735.
7. (c) Armstrong, R. W.; Brown, S. D.; Keating, T. A.; Tempest, P. A. In Combinatorial Chemistry. Synthesis and Application; Wilson, S. R.; Czarnik, A. W., Eds.; John Wiley: New York, 1997; pp. 153-190.
8. (d) Blackburn, C.; Guan, B.; Fleming, P.; Shiosaki, K.; Tsai, S. Tetrahedron Lett. 1998, 39, 3635.
9. (e) Hulme, C.; Peng, J.; Louridas, B.; Menard, P.; Krolikowski, P.; Kumar, N. V. Tetrahedron Lett. 39, 7227.
10. (a) Ugi, I. Angew. Chem., Int. Ed. Engl. 1962, 1, 8.
11. (b) Ugi, I.; Steinbruckner, C. Chem. Ber. 1961, 94, 734.
12. (c) Ugi, I.; Domling, A.; Horl, W. Endeavor 1994, 18, 115.
13. For a previous synthesis of imidazolines, see: Baumgartner, H.; O'Sullivan, A. C. Tetrahedron 1997, 53, 2775.
14. (a) Pigini, M.; Bousquet, P.; Carotti, A.; Dontenwill, M.; Gianella, M.; Moriconi, R.; Piergentili, A.; Quaglia, W.; Tayebati, S. K.; Brasili, L. Bioorg. Med. Chem. 1997, 5, 833.
15. (b) Harfenist, M.; Heuser, D. J.; Joyner, C. T.; Batchelor, J. F.; White, H. L. J. Med. Chem. 1996, 39, 1857.
16. (c) Jackson, H. C.; Griffin, I. J.; Nutt, D. J. Br. J. Pharmacol. 1991, 104, 258.
17. (d) Tibirica, E.; Feldman, J.; Mermet, C.; Gonon, F.; Bousquet, P. J. Pharmacol. 1987, 134, 1.
18. (a) Gilbert, I.; Rees, D. C.; Richardson, R. S. Tetrahedron Lett. 1991, 32, 2277.
19. (b) Jones, R. C. F.; Ward, G. J. Tetrahedron Lett. 1988, 29, 3853.
20. 3CN to 100% over 15 min. HPLC was interfaced with APCI techniques.
21. Note: evaporation was performed over only 2 hours at 65°C in vacuo with a SAVANT evaporator for compounds 3 to 8.
22. The N-Boc-α-amino aldehydes may be purchased from Peninsula laboratories.
23. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
24. Performed in a SAVANT® evaporator for 2 hours.
25. +).
26. (a) Booth, R. J.; Hodges, J. C. J. Am. Chem. Soc. 1997, 119, 4882.
27. (b) Flynn, D. L.; Crich, J. Z.; Devraj, R. V.; Hockerman, S. L.; Parlow, J. J.; South, M. S.; Woodward, S. J. Am. Chem. Soc. 1997, 119, 4874.
28. Purchased from Argonaut® technologies (PS-DIEA - polystyrene bound disopropylethylamine).
29. Note the following limitation: imidazoline products containing hydroxyl groups are removed during the scavenging step.