Selective Solid Phase Synthesis of Ureas and Hydantoins from Common Phenyl Carbamate Intermediates

Journal of Organic Chemistry

Volumn 62, Issue 20, 1997, Pages 6968-6973

  Xiao, Xiao Yi ^a,b   Ngu, Khehyong ^a,c   Chao, Corinne ^a   Patel, Dinesh V ^a,c  

^a AFFYMAX RESEARCH INSTITUTE   (United States)

^b IRORI Quantum Microchemistry   (United States)

^c Versicor Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001149799     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo971087i     Document Type: Article

References (21)

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5. The five-membered hydantoins and six-membered diketopiperazines are two common examples of cyclic dipeptidomimetic motifs.
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18. Tenta Gel S resin is from RAPP Polymere: 90 μ. Initial loading: 0.23 mmol/g, AM: acid cleavable linker.
19. The reaction was usually continued until the resin became ninhydrin negative, signifying the disappearance of starting amine. Later experiments suggested that the carbamate formation was usually complete in 1 h.
20. Simple hydrolysis of phenyl carbamate 1 would also result in the release of phenol accompanied by the formation of corresponding free amine of 1. This possibility was ruled out because the final resin was ninhydrin negative. Therefore, it was appropriate to view the amount of phenol release from 1 upon DIEA treatment as an indication of the extent of cyclization to hydantoin. Similarly, since phenyl carbamate 1 was reasonably stable to storage, phenoi release upon reaction with phenethylamine was used as a measure of urea formation.
21. Other organic bases like triethylamine and N-methylmorpholine were also tested and and found to give less satisfactory results.