Diisopropylcarbodiimide: A novel reagent for the synthesis of 1,3,4- oxadiazoles on solid-phase

Synlett

Volumn , Issue 1, 2000, Pages 131-133

  Brown, Bethany J ^a   Clemens, Ian R ^a   Neesom, James K ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Acylations; Amides; Cyclisations; Heterocycles; Solid phase synthesis

Indexed keywords

1,3,4 OXADIAZOLE DERIVATIVE; CYANAMIDE;

ACYLATION; ARTICLE; CYCLIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; STRUCTURE ANALYSIS;

EID: 0033978534     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (19)

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14. A selection of amide coupling reagents e.g. O-(7-Azabenzotriazole-l-yl)-N,N,N',N'-tetramethyluronium heaxfluorophosphate (HATU®), PyBOP®, DCC, and DIPCDI, were employed to attempt this cyclisation but only carbodiimides gave respectable yields of the desired oxadiazoles.
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16. Coupling the free diacid led to considerable cross-linking of the resin, resulting in terephallicacid diamide impurity in products after cleavage from the solid support.
17. Reaction conditions: The resin bound 1,2-diacylhydrazine (200mg, 0.12mmol) was treated with DIPCDI (6mmol) in DMF (2ml) and heated at 100°C for 18 hours. The resin was then washed with DMF(×5) and DCM(×5). The resulting oxadiazoles were then cleaved from the support with TFA:DCM (50:50).
18. In the synthesis of other related systems we have subsequently demonstrated these conditions are also compatible with Wang and 2-chlorotrityl linkages.
19. In preliminary studies, we have synthesised the 4-methoxyphenyl derivative in comparable yield and purity, using this generic approach.