Phosphorus oxychloride → N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl)-4-piperidineacetamide

Participants

Reaction Steps

A mixture of 52.4 parts of 1-(phenylmethyl)-4-piperidineacetic acid hydrochloride, 38.7 parts of N4 -[(4-fluorophenyl)methyl]- 4,5-pyrimidinediamine and 765 parts of phosphoryl chloride was stirred and refluxed for 30 minutes. The reaction mixture was evaporated. The residue was decomposed with ice water. The product was extracted with dichloromethane after treatment with sodium hydroxide. The extract was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 37 parts (61%) of N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl)-4-piperidineacetamide; mp. 157.3° C. (interm. 45).

Provenance & Evidence