Synthesis of azepane scaffolds on solid support for combinatorial chemistry

Tetrahedron Letters

Volumn 40, Issue 33, 1999, Pages 6005-6008

  Gauzy, Laurence ^a   Merrer, Yves Le ^a   Depezay, Jean Claude ^a   Clerc, François ^b   Mignani, Serge ^b  

^a UNIVERSITÉ PARIS DESCARTES   (France)

^b SANOFI   (France)

Author keywords

Azepane; Combinatorial chemistry; Rink resin; Solid phase synthesis

Indexed keywords

AMMONIA; AZEPANE; AZEPINE DERIVATIVE; CARBON; EPOXIDE; RESIN; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; SOLID;

EID: 0033551756     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01247-2     Document Type: Article

References (26)

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17. Deprotection was carried out by 30% piperidine in DMF.
18. The amine 8 was prepared from the commercialy available Fmoc-Rink linker by amidification with benzylamine in presence of DCC and N,N-diisopropylethylamine, and subsequent Fmoc removal with piperidine in THF.
19. The formation of the desired azepane was indicated by the disappearance of the free amine of the linker. In order to quantify reaction yields directly on beads, we have used a protocol involving ninhydrin.
20. 2O (2 × 10 mL), then dried under reduced pressure to give 2. Resin loading of "Rink-azepane resin" 1 was determined to be 0.23 mmol/g by ninhydrin test.
21. Degradation has been confirmed by heating the deprotected Rink resin in DMF at 80°C during 2, 5 or 7 days. Treatment of each batch with N-Fmoc glycine (DIC, DMAP) and subsequent measurement of the Fmoc group introduced allowed to quantify the remaining free amino group after heating. The ratio of remaining amine relative to the initial quantity was respectively 87, 35 or 26% after heating during 2, 5 or 7 days.
22. For example, without caping free amines, the azepane 4 isolated after benzoylation and cleavage was contamined with benzamide.
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24. 2O (2 × 1 mL) and drying under reduced pressure. After protection of the remaining free amines as carbamates, only 0.07 mmol/g of Rink-linker remains free.
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