Phosphorus oxychloride → ethyl 4-[[6-chloro-7-[(4-fluorophenyl)methyl]-7H-purin-8-yl]amino]-1-piperidinecarboxylate

Participants

Reaction Steps

A mixture of 50.7 parts of ethyl 4-[[7-amino-1-[(4-fluorophenyl)-methyl]oxazolo[5,4-d]pyrimidin-2(1H)-yliden]amino]-1-piperidinecarboxylate and 3050 parts of phosphoryl chloride was stirred for 90 minutes at reflux temperature. The reaction mixture was evaporated. The residue was poured into ice water. The whole was treated with ammonium hydroxide. The product was extracted with 4-methyl-2-pentanone. 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 21.6 parts (41.5%) of ethyl 4-[[6-chloro-7-[(4-fluorophenyl)methyl]-7H-purin-8-yl]amino]-1-piperidinecarboxylate; mp. 126.6° C. (compound 25).

Provenance & Evidence