反应详情

温度

100 °C

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.051 g, 0.155 mmol) in dry dioxane (0.7 mL) add N-[4-(4-bromo-phenyl)-thiazol-2-yl]-cyclopropylmethylamine (0.043 g, 0.14 mmol), tris(dibenzylideneacetone)dipalladium(0) (3.2 mg, 0.0035 mmol), Xantphos (4.1 mg, 0.014 mmol) and diisopropylethylamine (0.049 mL, 0.28 mmol) at room temperature. Purge the reaction mixture with nitrogen and heat the mixture at 100° C. overnight. Cool the reaction mixture to room temperature, dilute with DCM (50 mL) and filter through Celite®. Concentrate the filtrate 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 (0:100 to 25:75 EtOAc/hexane over 33 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-{4-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-phenylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.076 g, 97%) as a colorless oil.

1. customPurge the reaction mixture with nitrogen
2. temperatureCool the reaction mixture to room temperature
3. additiondilute with DCM (50 mL)
4. filtrationfilter through Celite®
5. concentrationConcentrate the filtrate in vacuo
6. dissolutionDissolve the residue in DCM
7. customload the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 25:75 EtOAc/hexane over 33 min; 35 mL/min)