Ethyl isonicotinate → Ethyl 1-[[4-[(6-chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl]carbonyl]-4-piperidinecarboxylate

Participants

Reaction Steps

A mixture of 4-[(6-chloro-2-naphthyl)sulfonyl)-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazine carboxylic acid (0.18 g) obtained in Example 110, ethyl isonicotinate (0.068 ml) and 1-hydroxy-1H-benzotriazole monohydrate (0.068 g) in DMF (4.4 ml) was combined with WSC (0.096 g) and stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and partitioned between saturated aqueous sodium bicarbonate and methylene chloride. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified on a CHP-20 column (water→1% 1N hydrochloric acid-containing 30% aqueous solution of acetonitrile) to obtain ethyl 1-[[4-[(6-chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl]carbonyl]-4-piperidinecarboxylate as a colorless powder. Then a mixture of this material with 1N sodium hydroxide (1.14 ml) and methanol (4.0 ml) was stirred at 40° C. for 30 minutes. The reaction mixture was cooled, and the reaction system was adjusted at pH 5 with 1N hydrochloric acid, and concentrated under reduced pressure. The residue was purified on a CHP-20 column (water→1% conc. aqueous ammonia-containing 25% aqueous solution of acetonitrile) to obtain the title compound (0.07 g) as a colorless powder.

Provenance & Evidence