反应详情

温度

0 °C

A solution of tert-butyl 4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazine-1-carboxylate (250 mg, 0.62 mmol) in CH2Cl2 (2.5 mL) at 0° C. was treated with TFA (2.5 mL) and stirred at 0° C. for 1.5 h. After this time, the solvents were evaporated in vacuo and the excess TFA removed by azeotroping with toluene (3×10 mL). The residue was suspended in CHCl3 (3 mL) and pyridine (3 mL) and treated with benzenesulfonyl chloride (1.1 eq, 0.68 mmol, 0.09 mL), warmed to room temperature and stirred for 12 h. The solvents were removed in vacuo and the residue partition between water (5 mL) and EtOAc (5 mL). The aqueous layer was extracted with EtOAc (2×5 mL) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. Column chromatography (hexane-EtOAc, 1:1) gave the product (107 mg, 39% for two steps) as a yellow solid; 1H-NMR (500 MHz, DMSO-d6) 3.09 (br s, 8H, 2× piperazine N(CH2)2), 7.08 (br s, 2H, NH2), 7.67-7.70 (m, 2H, phenyl H-3 & H-5), 7.74-7.78 (m, 3H, phenyl H-2, H-4 & H-6), 8.16 (s, 1H, pyridine H-6);

1. customAfter this time, the solvents were evaporated in vacuo
2. customthe excess TFA removed
3. customby azeotroping with toluene (3×10 mL)
4. temperaturewarmed to room temperature
5. stirringstirred for 12 h
6. customThe solvents were removed in vacuo
7. customthe residue partition between water (5 mL) and EtOAc (5 mL)
8. extractionThe aqueous layer was extracted with EtOAc (2×5 mL)
9. dry with materialthe combined organic extracts were dried (MgSO4)
10. concentrationconcentrated in vacuo
11. customColumn chromatography (hexane-EtOAc, 1:1) gave the product (107 mg, 39% for two steps) as a yellow solid