Solid-phase synthesis of unsymmetrical ureas through the use of Kenner safety-catch linker

Tetrahedron Letters

Volumn 44, Issue 4, 2003, Pages 811-814

  Fattori, Daniela ^a   D'Andrea, Piero ^a   Porcelloni, Marina ^a  

^a Menarini Ricerche SpA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACETONITRILE DERIVATIVE; AMINE; ISOCYANATE; UREA DERIVATIVE;

ARTICLE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PROTON NUCLEAR MAGNETIC RESONANCE; SOLID; SYNTHESIS; TECHNIQUE;

EID: 0037455030     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(02)02656-4     Document Type: Article

References (17)

1. Smith R.A., Barbosa J., Blum C.L., Bobko M.A., Caringal Y.V., Dally R., Johnson J.S., Katz M.E., Kennure N., Kingery-Wood J., Lee W., Lowinger T.B., Lyons J., Marsh V., Rogers D.H., Swartz S., Walling T., Wild H. Bioorg. Med. Chem. Lett. 11:2002;2775-2778.
2. Muller G., Albers M., Fisher R., Hessler G., Lehmann T.E., Okigami H., Tajimi M., Bacon K., Rolle T. Bioorg. Med. Chem. Lett. 11:2002;3019-3021.
3. Hutchins S.M., Chapman K.T. Tetrahedron Lett. 35:1994;4055-4058.
4. Wang G.T., Chen Y., Wang S., Sciotti R., Sowin T. Tetrahedron Lett. 38:1997;1895-1898.
5. Paio A., Ferritto C.R., Seneci P., Ciriaco M. J. Comb. Chem. 3:2001;354-359.
6. Zheng C., Combs A. J. Comb. Chem. 4:2002;38-43.
7. Ingenito R., Fattori D., Bianchi E., Pessi A. J. Am. Chem. Soc. 121:1999;11369.
8. Fattori D., Kinzel O., Ingallinella P., Bianchi E., Pessi A. Bioorg. Med. Chem. Lett. 12:2002;1143-1147.
9. Kenner G.W., McDermott J.R., Sheppard R.C. Chem. Commun. 1971;636-637.
10. Backes B.J., Virgilio A.A., Ellman J.A. J. Am. Chem. Soc. 118:1996;3055-3056.
11. Fluka 08559 (1) and Novabiochem (2).
12. A batch of resin swelled in 1:1 THF/DCM was treated with phenyl isocyanate (10 equiv.) and DIPEA (10 equiv.) and shaken at rt for 12 h. Then it was washed with THF, DCM, THF, diethyl ether and dried in vacuo.
13. A batch of activated resin was treated with 1.2 equiv. of p-methoxybenzylamine in 1.5 mL of solvent for 12 h. Then, 2 equiv. of isocyanate resin were added together with 2 mL of THF and the resulting mixture was shaken for an additional 2 h. Filtration and concentration in vacuo (Genevac HT-4 apparatus) afforded the desired crude compounds.
14. 2 (resin 1) or iodoacetonitrile (resin 2). The quantity of p-methoxyphenyl amide obtained following cleavage with p-methoxybenzyl-amine and treatment with isocyanate resin, was used to evaluate the starting resin loading.
15. HPLC was carried out on a 50×4.6 mm, 3 μm LUNA RPC18 column (Phenomenex) or on a Symmetry RPC18, 100×4.6 mm column (Waters) using Water Alliance 2695 equipment with a gradient of acetonitrile in water (1 mL/min, 0.1% TFA acid buffer, gradient 10-80 over 12 min) and UV detection at 220 nm.
16. Loading of the isocyanate was prolonged for 5 days instead of 12 h.
17. a (DMSO) 17.5; data from http://daeiris.harvard.edu/pKa/pKa.html.