A convenient, efficient method for synthesising indole-3-substituted-2-benzimidazoles and benzothiazoles was carried out using N-arylation followed by condensation-oxidation protocol. N-arylation of 1H-indole-3-carbaldehyde was carried out via CuI/DMED to yield 1-(3-((tert-butylsulfonyl)methyl)phenyl)-1H-indole-3-carbaldehyde. Condensation using various o-phenylenediamines in the presence of CAN/DMF as oxidant furnished the desired 2-(1-(3-((tert-butylsulfonyl)methyl)phenyl)-1H-indol-3-yl)-1H-benzo[d]imidazole. In addition to simple o-phenylenediamines, 1,2-arylenediamines substituted with withdrawing and donating groups, heterocyclic-2,3-phenylene diamines are well tolerated and give good yields of up to 74% yield. As simple reaction between o-phenylenediamines and 1H-substituted indole-3-carboxyaldehyde give indole-3-substituted-2-benzimidazoles with moderate to good yields. These novel indole-derived benzimidazoles and benzothiazoles have shown their efficacy as anti-cancer agents with various cancer K-562, MDA-MB231, colon-205 cell lines.
Background:
1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity
Objective:
The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (anti-migraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc
Method:
Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4-methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products
Results:
A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol-1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4-triazole were prepared
Conclusion:
Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4-methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.
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