反应详情

A solution of tert-butyl 4-{4′-[(1-{[(cyanomethyl)amino]carbonyl}-3-methylbutoxy)methyl][1,1′-biphenyl]-4-yl}-1-piperazinecarboxylate (115 mg, 0.21 mmoles) in tetrahydrofuran (3.5 mL) was treated with methanesulfonic acid (30 μL, 0.4 mmoles). The same amount of acid was added 5 times at 1.5 hour intervals and stirred overnight. Acid addition was resumed and two more portions (30 μL, 0.4 mmoles) were added, with a 1.5 hour interval. The reaction was diluted with diethyl ether, ethylacetate, sat. aq. sodium bicarbonate. The phases were separated and the organic phase was dried over sodium sulfate and concentrated under reduced pressure. The product was chromatographed (1% sat. aq. ammonium hydroxyde, 9% methanol, 90% dichloromethane) to obtain 77 mg N-(cyanomethyl)-4-methyl-2-{[4′-(1-piperazinyl)[1,1′-biphenyl]-4-yl]methoxy}pentanamide, a yellowish solid.

1. additionThe same amount of acid was added 5 times at 1.5 hour intervals
2. additionAcid addition
3. additiontwo more portions (30 μL, 0.4 mmoles) were added, with a 1.5 hour interval
4. customThe phases were separated
5. dry with materialthe organic phase was dried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe product was chromatographed (1% sat. aq. ammonium hydroxyde, 9% methanol, 90% dichloromethane)