Synthesis of a highly functionalized rigid template by solid phase azomethine ylide cycloaddition

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 20, 1996, Pages 2441-2444

  Bicknell, Andrew J ^a   Hird, Nicholas W ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PYRROLIDINE DERIVATIVE;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REACTION ANALYSIS; TECHNIQUE;

EID: 0030598197     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00447-7     Document Type: Article

References (14)

1. 1. (a) Baum, R.M. C & E. N. Feb. 7, 1994, 20.
2. (b) Gallop, M.A.; Barrett, R. W.; Dower, W.J.; Fodor, S.P.A.; Gordon, E.M.; J. Med. Chem. 1994, 37, 1233
3. (c) Gordon, E.M.; Barrett, R.W.; Dower, W.J.; Fodor, S.P.A.; Gallop, M.A.;. J. Med. Chem. 1994, 37, 1385
4. (d) Terrett, N.K.; Gardner, M.; Gordon, D.W.; Kobylecki, R.J.; Steele, J. Tetrahedron, 1995, 51, 8135.
5. 2. Hermkens, P.H.H.; Ottenheijm, H.C.J.; Rees, D.; Tetrahedron, 1996, 51, 4527.
6. 3. B.C. Hamper, D.R. Dukesherer, M.S. South. Tet. Letts., 1996, 37, 3671
7. 4. A. M. Costero, M. Pitarch and M. Luz Cano, J. Chem Res (S), 1994, 316
8. 5. Murphy, M.M.; Schullek, J.R.; Gordon, E.M.; Gallop, M.A. J. Am. Chem. Soc., 1995, 117, 7029
9. 6. Typical Procedure: To 0.3mmol deprotected Fmoc Ala Wang resin(0.52mmol/g) (dried in vacuo) suspended in dry dichloromethane (10ml) in a round bottom flask under argon was added 4-nitrobenzaldehyde (3mmol) and the mixture shaken overnight. The resin was removed by filtration and washed with 3×20ml dry dichloromethane and dried in vacuo.
10. 7. As 6 except resin was suspended in dry toluene (10ml) in a round bottom flask under argon, to which was added aldehyde (3mmol) and the mixture was heated to reflux overnight.
11. 8. Typical Procedure: 0.16mmol resin was suspended in dry toluene (10ml) in a round bottom flask under argon and N-phenylmaleimide (1.6mmol) was added. The mixture was refluxed for 24h after which the resin was filtered and washed successively with toluene, dioxane and ether (each 3×10ml) and dried under high vacuum. The resin was cleaved by suspension in trifluoroacetic acid/dichloromethane (1:1) for 1h, followed by washing with dichloromethane.
12. 9. Grigg, R.; Gunaratine, H.Q.N.; Tet. Letts., 1983, 24, 4457.
13. 10. Typical Procedure: 0.1mmol resin was suspended in 1:1 (v/v) phenylacetylchloride in dichloromethane (1ml) to which leq of pyridine was added, and the mixture was shaken for 16h. The resin was removed by filtration and washed successively with dichloromethane, methanol, methanol-water (3:1), methanol and dioxane (each 3×10ml). The coupling procedure was repeated, and the resin was cleaved as described above.
14. 11. Barn, D.R.; Morphy, J.R.; Rees, D.C.; Tet. Letts., 1996, 37, 3213.