Rapid microwave-assisted liquid-phase combinatorial synthesis of 2-(arylamino)benzimidazoles

Journal of Combinatorial Chemistry

Volumn 4, Issue 4, 2002, Pages 359-361

  Bendale, Pravin M ^a   Sun, Chung Ming ^a  

^a NATIONAL DONG HWA UNIVERSITY   (Taiwan)

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ARTICLE;

EID: 0012760228     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc0200080     Document Type: Article

References (44)

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43. From comparison results of the microwave library with the conventionally generated library of benzimidazoles, the reaction time of microwave heating was reduced to 16 min from the regular 10h. If the overall average purity of each library member is considered, the purities of the microwave library and the purities of the conventional library are actually comparable at 83% and 87%, respectively.
44. All microwave-assisted reactions were performed in a 100 mL round-bottom flask (attached to the reflux condenser) with a Sharp domestic microwave oven at a frequency of 2450 Hz (900 W). A typical procedure for the synthesis of 5 (Table 1, entry 15) is the following. A mixture of polymer-supported diamine (510 mg), DCC (5 equiv), 10 mL of methanol, and 5 equiv of phenyl isothiocyanate was irradiated in a microwave cavity with an output at 50% (450 W) for 10 min. Upon completion of the reaction, cold diethyl ether (20 mL) was added to the reaction mixture to precipitate the PEG-bound benzimidazole. The precipitate was then collected on a sintered glass funnel and thoroughly washed with diethyl ether (20 mL × 3). PEG-bound benzimidazole was then dried under vacuum to yield the cyclized benzimidazole in quantitative yield. Finally, the resulting PEG-bound benzimidazole was cleaved in a microwave cavity by using LiBr (5 equiv) and DBU (3 equiv) in 10 mL of methanol. After 4 min of reaction, the detached MeO-PEG-OH was precipitated by adding cold diethyl ether. The polymer was filtered, and the combined filtrate was passed through an SPE (solid-phase extraction) short cartridge to remove a trace amount of PEG and DBU. The final compound was dried to offer the corresponding crude product in 92% yield with 91% HPLC purity.