反应详情

To a solution of tert-butyl 4-(2-(3-methylisoxazol-5-ylamino)-2-oxoethyl)piperazine-1-carboxylate (0.087 g, 0.27 mmol) in anhydrous dichloromethane (3 ml) was added TFA (3.7 ml). The reaction mixture was stirred at room temperature for 1 h and 45 min, then the solvent was removed in vacuo and the residue was dried in vacuo over P2O5. To a solution of this material (supposedly 0.27 mmol) in isopropanol (5 ml) was added 2-amino-4,5-dichloro-3-nitro-pyridine (0.050 g, 0.24 mmol) followed by diisopropylethylamine (0.22 ml, 1.25 mmol). The reaction mixture was stirred at 45° C. for 18 h, then allowed to cool to room temperature, and diluted with isopropanol (6 ml). The precipitate was collected by filtration, washed with isopropanol (2×6 ml), and diethyl ether (2×6 ml), and dried. The title compound was obtained as an orange solid (0.042 g). The filtrate was concentrated in vacuo, and purification of the residue by chromatography (10 g isolute column) on elution with dichloromethane/ethyl acetate (v/v; 1:1), and 2% methanol in dichloromethane/ethyl acetate (v/v; 1:1) afforded an additional 0.025 g of the product (overall yield: 63%). 1H-NMR (500 MHz, DMSO-d6) 2.18 (s, 3H, CH3), 2.63 (s, 4H, piperazine N(CH2)2), 3.28 (s, 2H, NCH2CO), 3.10 (s, 4H, piperazine N(CH2)2), 6.15 (s, 1H, isoxazole C—H), 7.00 (s, 2H, NH2), 8.07 (s, 1H, 6-H), 11.37 (s, 1H, CONH);

1. customthe solvent was removed in vacuo
2. dry with materialthe residue was dried in vacuo over P2O5
3. stirringThe reaction mixture was stirred at 45° C. for 18 h
4. temperatureto cool to room temperature
5. filtrationThe precipitate was collected by filtration
6. washwashed with isopropanol (2×6 ml), and diethyl ether (2×6 ml)
7. customdried