Solid phase synthesis of ureas of secondary amines via carbamoyl chloride

Tetrahedron Letters

Volumn 38, Issue 11, 1997, Pages 1895-1898

  Wang, Gary T ^a   Chen, Yuanwei ^a   Wang, Sheldon ^a   Sciotti, Richard ^a   Sowin, Thomas ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; UREA DERIVATIVE;

ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; STEREOSPECIFICITY;

EID: 0031575734     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00245-1     Document Type: Article

References (13)

1. 1. Reviews: (a). Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res. 1996, 29, 144-154.
2. (b) Ellman, J. A. Acc. Chem. Res. 1996, 29, 132-143.
3. (c). Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251.
4. (d). Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P.A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401.
5. 2. Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600
6. 3. Hermkens, P. H. H.; Ottenheilm, H. C., Rees, D. Tetrahedron 1996, 52, 4527-4559.
7. 4. (a) Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1994, 35, 4055-4058.
8. (b) Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1995, 36, 2583-2586.
9. 5. Burgess, K.; Linthicum, D. S.; Shin, H. Angew. Chem. Int. Ed. Engl. 1995, 34, 907-909.
10. 6. We thank Dr. Doug Kalvin for a sample of Fmoc-isonipecotic acid.
11. 7. The reaction has also been performed successfully using triphosgene following a slightly different procedure. To preswelled resin (50-100 mg) in DCM (1-2 mL) at room temperature was added diisopropylethyl amine (10 equivalents) followed by triphosgene (3 equivalents). The reaction was allowed to shake for 1-1.5 hours then drained, washed with DCM (4X), then dried under vacuum.
12. 8. An Advanced ChemTech Model 396 multiple peptide synthesizer was used. This instrument allows 96 parallel reactions with 60 individual monomers (starting materials).
13. 9. The signal of evaporative light scattering detection is independent of the absorption spectrum of the analyte. Elfakir, C.; Lafosse, M.; Dreux, M. J. Chromatography 1990, 513, 354-359.