2- 叔丁胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a reaction flask 283.5 ml dimethylsulfoxide, 29.83 g 1-(2-hydroxyethyl)piperazine (0.229 mol), 12.08 g sodium carbonate (0.144 mol), 56.70 g ter-butyl-6-chloro-2-methylpyrimidin-4-yl-(5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl)carbamate (0.114 mol) were charged at a temperature of about 25° C. and the reaction mixture was kept under these conditions for about five hours. At the end of the reaction, 760 ml water were added, the mixture was kept under stirring for about 30 minutes and the formed solid was filtered, washed with water (4×260 ml) and suspended in 440 ml methanol. 42.88 g di-terbutylamine (DBTA, 0.120 mol) were added, the temperature was brought to the solvent reflux value and 15.19 g tromethamol (TRIZMA) (0.125 mol) were added. The temperature was brought to about 25° C. and the formed solid was filtered, washed with methanol (2×45 ml) and dried in oven under vacuum at a temperature of about 50° C. for eight hours to give 44.51 g dasatinib. were added the formed solid was filtered washed with water (4×260 ml) were added was brought to about 25° C. the formed solid was filtered washed with methanol (2×45 ml) dried in oven under vacuum at a temperature of about 50° C. for eight hours

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a reaction flask 283.5 ml dimethylsulfoxide, 29.83 g 1-(2-hydroxyethyl)piperazine (0.229 mol), 12.08 g sodium carbonate (0.144 mol), 56.70 g ter-butyl-6-chloro-2-methylpyrimidin-4-yl-(5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl)carbamate (0.114 mol) were charged at a temperature of about 25° C. and the reaction mixture was kept under these conditions for about five hours. At the end of the reaction, 760 ml water were added, the mixture was kept under stirring for about 30 minutes and the formed solid was filtered, washed with water (4×260 ml) and suspended in 440 ml methanol. 42.88 g di-terbutylamine (DBTA, 0.120 mol) were added, the temperature was brought to the solvent reflux value and 15.19 g tromethamol (TRIZMA) (0.125 mol) were added. The temperature was brought to about 25° C. and the formed solid was filtered, washed with methanol (2×45 ml) and dried in oven under vacuum at a temperature of about 50° C. for eight hours to give 44.51 g dasatinib. were added the formed solid was filtered washed with water (4×260 ml) were added was brought to about 25° C. the formed solid was filtered washed with methanol (2×45 ml) dried in oven under vacuum at a temperature of about 50° C. for eight hours

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of K2CO3 (200 g, 1.5 mole) in cyclohexane 200 mL and 1-bromo-3-chloropropane (540 gms, 3.4 mole) is added dropwise over a period of 1 h at 20C di-t-butyl amine (289 g, 2.24 mole). After complete addition the reaction is allowed to stir for an additional 20 h. The crude reaction mixture is filtered and then washed with saturated NaCl (3×100 mL). The organic phase is extracted with 3N HCl (3×100 mL). The resulting aqueous phase, containing the desired product as the hydrochloric salt, is washed with hexanes (3×100 mL) to remove any residual BCP. The aqueous phase is subsequently basified with 50 wt % NaOH and extracted with cyclohexane (3×100 mL). After solvent removal 234 g (51% yield) of the title compound is isolated as a yellow oil. After complete addition the reaction The crude reaction mixture is filtered washed with saturated NaCl (3×100 mL) The organic phase is extracted with 3N HCl (3×100 mL) The resulting aqueous phase, containing the desired product as the hydrochloric salt is washed with hexanes (3×100 mL) to remove any residual BCP extracted with cyclohexane (3×100 mL)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred suspension of K2CO3 (200 g, 1.5 mole) in cyclohexane 200 mL and 1-bromo-3-chloropropane (540 gms, 3.4 mole) is added dropwise over a period of 1 h at 20° C. di-t-butyl amine (289 g, 2.24 mole). After complete addition the reaction is allowed to stir for an additional 20 h. The crude reaction mixture is filtered and then washed with saturated NaCl (3×100 mL). The organic phase is extracted with 3N HCl (3×100 mL). The resulting aqueous phase, containing the desired product as the hydrochloric salt, is washed with hexanes (3×100 mL) to remove any residual BCP. The aqueous phase is subsequently basified with 50 wt % NaOH and extracted with cyclohexane (3×100 mL). After solvent removal 234 g (51% yield) of the title compound is isolated as a yellow oil. After complete addition the reaction The crude reaction mixture is filtered washed with saturated NaCl (3×100 mL) The organic phase is extracted with 3N HCl (3×100 mL) The resulting aqueous phase, containing the desired product as the hydrochloric salt is washed with hexanes (3×100 mL) to remove any residual BCP extracted with cyclohexane (3×100 mL)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a reaction flask 283.5 ml dimethylsulfoxide, 29.83 g 1-(2-hydroxyethyl)piperazine (0.229 mol), 12.08 g sodium carbonate (0.144 mol), 56.70 g ter-butyl-6-chloro-2-methylpyrimidin-4-yl-(5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl)carbamate (0.114 mol) were charged at a temperature of about 25° C. and the reaction mixture was kept under these conditions for about five hours. At the end of the reaction, 760 ml water were added, the mixture was kept under stirring for about 30 minutes and the formed solid was filtered, washed with water (4×260 ml) and suspended in 440 ml methanol. 42.88 g di-terbutylamine (DBTA, 0.120 mol) were added, the temperature was brought to the solvent reflux value and 15.19 g tromethamol (TRIZMA) (0.125 mol) were added. The temperature was brought to about 25° C. and the formed solid was filtered, washed with methanol (2×45 ml) and dried in oven under vacuum at a temperature of about 50° C. for eight hours to give 44.51 g dasatinib. were added the formed solid was filtered washed with water (4×260 ml) were added was brought to about 25° C. the formed solid was filtered washed with methanol (2×45 ml) dried in oven under vacuum at a temperature of about 50° C. for eight hours