反应详情

To a solution of 6-(5-amino-[1,3,4]thiadiazol-2-ylthiomethyl)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.252 g, 0.59 mmol) in anhydrous DCE (1 mL), add a solution of cyclopropane carboxaldehyde (0.083 g, 1.2 mmol) in anhydrous DCE (1 mL) at room temperature. Add sodium tris(acetoxy)borohydride (0.38 g, 1.8 mmol) and a solution of glacial acetic acid (0.20 mL, 3.5 mmol) in anhydrous DCE (1 mL) to the reaction mixture at room temperature. Heat at reflux overnight, cool the reaction mixture to room temperature and add saturated aqueous NaHCO3 (25 mL) to the mixture. After stirring at room temperature for 1 h, extract the two-phase mixture with DCM (2×50 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 hexane/EtOAc over 33 min; 95:5 to 50:50 hexane/EtOAc over 33 min; 50:50 to 0:100 hexane/EtOAc over 30 min; 35 mL/min) to afford the desired intermediate (0.087 g, 31%). MS (ES+) m/z: 481.2 (M+H)+.

1. customat room temperature
2. temperatureHeat
3. temperatureat reflux overnight
4. extractionextract the two-phase mixture with DCM (2×50 mL)
5. dry with materialDry the combined organic extracts over Na2SO4
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. dissolutionDissolve the residue in DCM
9. customload the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 hexane/EtOAc over 33 min; 95:5 to 50:50 hexane/EtOAc over 33 min; 50:50 to 0:100 hexane/EtOAc over 30 min; 35 mL/min)