Dimethyl Sulfoxide → HCID 13769699, compound

Participants

Reaction Steps

To a stirred and cooled (below 10° C.) mixture of 5.52 parts of 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidine ethanol, 100 parts of dimethyl sulfoxide and 90 parts of methylbenzene were added 0.75 parts of a sodium hydride dispersion 50%. After stirring for 30 minutes at a temperature below 10° C., 2.5 parts of 2-bromothiazole were added and stirring was continued overnight while the mixture was allowed to reach room temperature. 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 1 part (14.5%) of 1-[(4-fluorophenyl)methyl]-N-[1-[2-(2-thiazolyloxy)ethyl]- 4-piperidinyl]-1H-benzimidazol-2-amine; mp. 156.5° C. (compound 72).

Provenance & Evidence