反应详情

(±)-4-(4-Chlorophenyl)-6-ethoxycarbonyl-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid (2.0 g) is dissolved in dimethylformamide (20 ml). 1-Hydroxybenzotriazole (HOBt, 0.81 g), N-dimethylaminopropyl-N'-ethylcarbodiimide hydrochloride (WSC, 1.10 g) and triethyl amine (0.77 ml) are added in order under ice-cooling, and the mixture is stirred. Ten minutes later, a solution of 2-methoxyaniline (0.65 g) dissolved in dimethylformamide (6 ml) is dropwise added to the reaction mixture, and the mixture is stirred at room temperature overnight. The reaction mixture is poured into water and extracted with toluene. The organic layer is washed with a 10% aqueous solution of hydrochloric acid, an aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate. After removing the solvent, the residue is recrystallized from ethanol to give 1.55 g of (±)-ethyl 4-(4-chlorophenyl)-6-(2-methoxyanilino)-carbonylmethyl-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4, 3-a][1,4]diazepine-6-carboxylate. 1/2 hydrate, melting point 136°-138° C.

1. temperaturecooling
2. additionis dropwise added to the reaction mixture
3. stirringthe mixture is stirred at room temperature overnight
4. extractionextracted with toluene
5. washThe organic layer is washed with a 10% aqueous solution of hydrochloric acid
6. dry with materialan aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate
7. customAfter removing the solvent
8. customthe residue is recrystallized from ethanol