A solid phase traceless synthesis of benzimidazoles with three combinatorial steps

Tetrahedron Letters

Volumn 40, Issue 43, 1999, Pages 7633-7636

  Smith, Jennifer M ^a   Krchňák, Viktor ^a  

^a SIDDCO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE; AMINE; ANILINE; BENZIMIDAZOLE DERIVATIVE; CHLORIDE; HETEROCYCLIC COMPOUND; NITROBENZENE DERIVATIVE; TIN CHLORIDE;

ACYLATION; ALKYLATION; ARTICLE; CYCLIZATION; SOLID; SYNTHESIS;

EID: 0033595867     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01560-9     Document Type: Article

References (21)

1. Rather than using a relative term 'traceless linker' we prefer to use the terminology traceless synthesis. For example, the Wang linker may leave a trace (carboxyl group) on a heterocyclic compound, however, it is suitable for the linkerless synthesis of peptides since the carboxyl group is an inherent part of peptides. On the other hand the silicon linker leaves a trace, the benzene ring, if the benzene moiety is not a part of the target compound.
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16. Smith, J.; Krokhina, G.; Gard, J.; Kaniszai, A.; Krchňák, V., submitted for publication
17. The reaction of o-phenylenediamine with aldehyde yields benzimidazoline, which is prone to oxidation to benzimidazole. We never detected this primary product.
18. Pre-weighted sample of the secondary amine resin was treated with 0.5 M Fmoc-Cl and 0.5 M DIEA in DCM for 1 h. After washing the resin with DCM and DMF, the Fmoc group was cleaved by 10 min treatment with 50% piperidine in DMF. The resin was washed with DMF, all washes were collected, the absorbance at 302 nm was measured, and the Fmoc release was quantified. Another sample of Fmoc-Cl treated secondary amine resin was cleaved by TFA for 1 h, TFA was evaporated, sample dissolved in MeOH and the purity evaluated by analytical HPLC.
19. Krchňák, V.; Padera, V. Bioorg. Med. Chem. Lett. 1998, 8, 3261-3264.
20. Analytical gradient HPLC profile was run on a ProC18 4.6 × 50 mm analytical column (YMC, Wilmington, NC), gradient 0-70% of ACN in 7 min. The purity was estimated based on analytical traces at 280 nm.
21. 6). One example is shown in Fig. 2.