Benzimidazole. 2-chloro-, amination

Similarly, thiazol-2-amine, 5-ethyl-l,3,4-thiadiazol-2-amine, 5-methylisoxazol-3-amine. 1,2,4-triazol-3-amine and benzimidazol-2-amine give the corresponding heterocyclic systems on reaction with 2-aza-l-chloro-l,3-bis(dimethylamino)-3-phenylpropenylium perchlorate.490... 

Benzimidazoles bearing a halogen in the activated 2-position show a remarkable reactivity in palladium catalyzed carbon-nitrogen bond forming reactions. TV-protected 2-chlorobenzimidazoles reacted smoothly with a series of amines (6.81.). The activity of the aryl halide, besides the ready coupling of the chloro derivative, is also emphasized by the low catalyst loading used.112... 

The 2-halo-substituted benzimidazoles, then, more or less readily react with ammonia, amines and hydrazines (80AHC 27)241,70AHC(12)103,74CRV279), It is likely that the formation of the 2-pyridinium compound (123) when cycloheptimidazolin-2(l//)-one reacts with phosphoryl chloride in pyridine occurs via the 2-chloro intermediate (Scheme 56). The sulfur function of benzimidazole-2-sulfonic acid can be displaced by amino or alkylamino groups. 

The amines selected from the modeling were successfully reacted with 2-chloro-5-(trifluoromethyl)-lH-benzimidazole according to the scheme outlined in Figure 12.9, with the products purified by reverse-phase HPLC. Two of the monomers failed and there is no screening data for these compounds. The functional activity at the human NPY-Y5 receptor was measured in a FLIPRCa + flux assay activated by endogenous PYY protein. Fifteen of the compounds demonstrated submicromolar potency in the... 

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