反应详情

To a stirred solution of NaBH4 (0.449 g, 11.81 mmol) in 50 mL of dry THF at 0° C. under N2 was added dropwise 48% w/w BF3 ether complex (1.47 mL, 11.68 mmol). The cooling bath was removed and the solution was stirred for 1 h at room temperature. Into the above was added dropwise a solution of 2-(4-nitro-phenyl)-N-[2-(4-phenyl-piperazin-1-yl)-ethyl]-acetamide 26a (0.55 g, 1.49 mmol) dissolved in THF (5 mL). The reaction mixture was refluxed for 6 h. After the solution cooled to room temperature, methanol (5 mL) was added slowly. The solvent was removed under reduced pressure and 10% HCl/MeOH (25 mL) was added to the residue and the solution refluxed for 1 h. Solid NaHCO3 was added and methanol was removed in vacuo. The mixture was extracted with EtOAc. The combined organic phase was dried over Na2SO4 and evaporated to give the crude product which was purified by chromatography (EtOAc/MeOH=4/1) to give 27a: 0.385 g (73% yield) as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ 1.62 (1H, bs, NH), 2.50 (2H, t, J=5.6 Hz, CH2—CH2NH), 2.58 (4H, t, J=4.8 Hz, (CH2)2N), 2.76 (2H, t, J=5.6 Hz, CH2Ar), 2.90-2.96 (4H, m, (CH2)2NH), 3.14 (4H, t, J=4.8 Hz, (CH2)2NPh), 6.85 (1H, t, J=7.2, ArH), 6.90 (2H, d, J=9.2, ArH), 7.25 (2H, t, J=9.2, ArH), 7.37 (2H, d, J=8.8, ArH), 8.15 (2H, d, J=8, ArH).

1. customThe cooling bath was removed
2. temperatureThe reaction mixture was refluxed for 6 h
3. temperatureAfter the solution cooled to room temperature
4. customThe solvent was removed under reduced pressure and 10% HCl/MeOH (25 mL)
5. additionwas added to the residue
6. temperaturethe solution refluxed for 1 h
7. additionSolid NaHCO3 was added
8. custommethanol was removed in vacuo
9. extractionThe mixture was extracted with EtOAc
10. dry with materialThe combined organic phase was dried over Na2SO4
11. customevaporated
12. customto give the crude product which
13. customwas purified by chromatography (EtOAc/MeOH=4/1)