2-Chlorobenzothiazole → N-[1-[2-(2-benzothiazolyloxy)ethyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine

Participants

Reaction Steps

To a stirred mixture of 5.5 parts of 4-[1-[(4-fluorophenyl)-methyl]-1H-benzimidazol-2-ylamino]-1-piperidineethanol and 135 parts of N,N-dimethylformamide were added 0.75 parts of a sodium hydride dispersion 50%. After stirring for 30 minutes at room temperature, 2.54 parts of 2-chlorobenzothiazole were added and the whole was further stirred for 3 hours. The reaction mixture was poured onto water and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 4.6 parts (61%) of N-[1-[2-(2-benzothiazolyloxy)ethyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine; mp. 147.0° C. (compound 67).

Provenance & Evidence