反应详情

To a mixture of HOBt hydrate (0.042 g, 0.27 mmol), EDC (0.037 g, 0.19 mmol), and 3-(3-(5-chloro-4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)-1-(3,3-diphenylpropyl)ureido)benzoic acid 78 (0.089 g, 0.13 mmol) was added DMF (1.5 mL). The reaction mixture was stirred at room temperature for 10 min and methylamine (2 mL, 2 M in MeOH, 4 mmol) was added. The reaction mixture was stirred at room temperature for 1 d and diluted with EtOAc. The organic phase was washed with water (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (eluted with 20% to 80% EtOAc in hexanes) gave 3-(((5-chloro-4-(4-((methylsulfonyl)amino)phenyl)-1,3-thiazol-2-yl)carbamoyl)(3,3-diphenylpropyl)amino)-N-methylbenzamide 79. Mass spectrum, calculated for C34H32ClN5O4S2 673.2; found 674.2 (M++1).

1. stirringThe reaction mixture was stirred at room temperature for 1 d
2. washThe organic phase was washed with water (1×), brine (1×)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by flash column chromatography on silica gel (eluted with 20% to 80% EtOAc in hexanes)