反应详情

To a solution of 1-5 (150 mg, 0.39 mmol), HOBT (63 mg, 0.46 mmol) and EDC (111 mg, 0.58 mmol) was added 3(S)-(ethynyl)-β-alanine ethyl ester hydrochloride (1-32) (U.S. Pat. No. 5,272,162; 82 mg, 0.46 mmol) and Et3N (80.7 μl, 0.58 mmol). The mixture was stirred at room tempertature under argon for 16 hours and then partitioned between EtOAc and 10% citric acid. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers then washed with saturated aqueous NaHCO3 followed by brine. Removal of the dried (MgSO4) solvent afforded a yellow oil which was purified by column chromatography (silica gel; hexane/EtOAc 1:1) to give 1-33 as an oil. Rf (silica; EtOAc/hexane 2:1) 0.57 ##STR51## N-{[7-(Piperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetyl}-3(S)-(ethynyl)-β-alanine ethyl ester (1-34)

1. custompartitioned between EtOAc and 10% citric acid
2. extractionThe aqueous phase was extracted with EtOAc (×3)
3. washthe combined organic layers then washed with saturated aqueous NaHCO3
4. customRemoval of the
5. dry with materialdried (MgSO4) solvent
6. customafforded a yellow oil which
7. customwas purified by column chromatography (silica gel; hexane/EtOAc 1:1)