反应详情

A solution of tert-butyl 4-(1-(pyridin-2-yl)ethyl)piperazine-1-carboxylate (1.1 eq, 1.10 mmol, 321 mg) in TFA (4 mL) and CH2Cl2 (4 mL) at 0° C. was stirred for 30 minutes and concentrated in vacuo. The remaining TFA was removed by azeotroping with toluene (3×10 mL) and drying at high vacuum for 2 h. Then the residue was reacted with 5-bromo-4-chloro-3-nitropyridin-2-amine (253 mg, 1.00 mmol) in iPrOH (5 mL) and DIPEA (2 mL) using the same procedure described for 2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide. After 18 h, the precipitate was filtered and washed with cold water (2×3 mL) and hexane (3 mL) to give the product (313 mg, 70% for two steps) as a yellow solid; 1H-NMR (500 MHz, DMSO-d6) 1.33 (d, J=6.7 Hz, 3H, CH3), 2.48-2.62 (2 m, 4H, piperazine N(CH2)2), 3.04-3.13 (m, 4H, piperazine N(CH2)2), 3.63-3.69 (m, 1H, CH), 6.95 (br s, 2H, NH2), 7.25 (dd, br, J=6.8, 5.2 Hz, 1H, pyridine H-5), 7.44 (d, J=7.8 Hz, 1H, pyridine H-3), 7.77 (td, J=7.7, 1.6 Hz, 1H, pyridine H-4), 8.13 (s, 1H, bromopyridine H-6), 8.50 (d, br, J=4.2 Hz, 1H, pyridine H-6);

1. concentrationconcentrated in vacuo
2. customThe remaining TFA was removed
3. customby azeotroping with toluene (3×10 mL)
4. customdrying at high vacuum for 2 h
5. filtrationthe precipitate was filtered
6. washwashed with cold water (2×3 mL) and hexane (3 mL)
7. customto give the product (313 mg, 70% for two steps) as a yellow solid