反应详情

To a stirred solution of neopentyl alcohol (105 mg, 1.19 mm ol) in THF (5 mL) at ambient temperature add sodium hydride (31 mg, 95%, 1.19 mmol) and continue stirring for 3 h at ambient temperature. Add a solution of 3-tert-butoxycarbonyl-7-chloro-6-(6-chloro-pyridazin-3-ylmethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (315 mg, 0.59 mmol) in THF (1 mL) and continue stirring overnight at ambient temperature and then at 60° C. for 1 h. Dilute with water, extract the reaction mixture three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (6:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[6-(2,2-dimethyl-propoxy)-pyridazin-3-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a clear oil (81 mg, 28%). MS (APCI+) m/z: 492 (M+H)+, 392 (M+H−Boc)+. Use a method similar to the General Procedure 1-4 to give the title compound as a white powder. MS (APCI+) m/z: 392 (M+H)+, m/z: 322 M+H−C5H11)+.

1. stirringcontinue stirring overnight at ambient temperature
2. waitat 60° C. for 1 h
3. extractionextract the reaction mixture three times with EtOAc
4. dry with materialdry over anhydrous Na2SO4
5. concentrationconcentrate in vacuo
6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (6:1)