Diisocyanates as scaffolds for combinatorial libraries. The solid-phase synthesis of bis-ureas from polymer-supported diisocyanates

Tetrahedron Letters

Volumn 37, Issue 45, 1996, Pages 8141-8144

  Scialdone, Mark A ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

UREA DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030569340     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01893-X     Document Type: Article

References (31)

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28. 28. Nitrogen analysis, when correcting for the added carbon, hydrogen and oxygen weight of the diisocyanate scaffold, is an accurate measure of substrate loading on the polymer and indeed correlates quite well with the observed yields of products.
29. -1 (Table 1) corresponding to the terminal isocyanate and the oxime-derived carbamate respectively. Nitrogen analysis (see footnote 28) verified high efficiency of loading. This resin was swelled again with dichloromethane and treated with excess amine in dichloromethane and shaken at room temperature overnight. The resulting resin was filtered, washed and dried as before and IR (KBr) showed complete loss of the isocyanate peak. This resin was swelled again with dichloromethane and treated with trapping amine (excess if volatile under high vacuum or 1 eq. if non-volatile) in toluene and the vial was sealed and heated to 75°C overnight. After allowing to cool, sampling of the resin and taking an IR can be done to see if the thermolytic release of the isocyanate is complete. In the examples illustrated in Table 2, reaction times between 24 and 48 hours were sufficient for complete reaction. Filtration followed by washing with copious amounts of dichloromethane then methanol at least three times and evaporation of the solvents under vacuum gave the bis-urea products which were analyzed directly without purification.
30. 30. All new compounds displayed spectroscopic data consistent with their structural assignments. Low resolution mass spectra were obtained with a VG Trio-2000 quadrapole mass spectrometer using the electrospray atmospheric pressure chemical ionization (APCI) technique. High resolution mass spectra were obtained using a ZAB 2F magnetic sector high resolution mass spectrometer. HPLC analyses were performed on a Hewlett-Packard 1090 Liquid chromatography system using a photodiode array detector and a Zorbax SB-C18 column, 2.1 × 150 mm, starting at 5% acetonitrile/water/0.1% HOAc -> 99.9% acetonitrile/0.1% HOAc.
31. 31. Mechanistic studies of the thermolytic cleavage of polymer-supported oxime-derived carbamates are currently in progress and results will be reported in due course.