反应详情

To a stirred solution of tert-butyl (RS)-2-(4-amino-3-bromophenyl)morpholine-4-carboxylate (100 mg, example 28a) in dichloromethane (2 ml) was added triphosgene (31 mg). A solution of sodium carbonate (59 mg) in water (2 ml) was then added. The reaction mixture was stirred at room temperature for 2.5 hours. TLC showed all the starting material had reacted. A solution of 6-chloropyridin-3-amine (36 mg, CAS 5350-93-6) in dichloromethane (2 ml) was then added and the reaction mixture was stirred at room temperature for a further 2 hours. TLC showed the reaction was complete. The reaction mixture was poured into dichloromethane and extracted with water. The organic phase was separated, dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: 0% to 80% EtOAc in heptanes) to give (RS)-2-{3-bromo-4-[3-(6-chloro-pyridin-3-yl)-ureido]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (47 mg, 33%) as an off-white solid. MS (ISP): 515.2 ([{37Cl81Br}M+H]+), 513.2 ([{37Cl79Br or 35Cl81Br}M+H]+), 511.0 ([{35Cl79Br}M+H]+), 459.0 ([{37Cl81Br}M+H—C4H8]+), 457.0 ([{37Cl79Br or 35Cl81Br}M+H—C4H8]+), 454.9 ([{35Cl79Br}M+H—C4H8]+).

1. customhad reacted
2. stirringthe reaction mixture was stirred at room temperature for a further 2 hours
3. extractionextracted with water
4. customThe organic phase was separated
5. dry with materialdried over sodium sulphate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (SiO2; gradient: 0% to 80% EtOAc in heptanes)