反应详情

DIPEA (110.8 mg, 0.147 mL, 0.85 mmol) was added to a stirred solution of biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (100 mg, 0.22 mmol) in DMF (3 mL). HOBT (28.3 mg, 0.2 mmol) and EDCI.HCl (91.25 mg, 0.47 mmol) were then added. After 2 minutes 3-methyl-thiophene-2-carboxylic acid (27 mg, 0.19 mmol) was added and the resulting mixture was stirred overnight. The reaction mixture was diluted with cold water. The product was extracted with ethyl acetate and the ethyl acetate layer was washed with NaHCO3 solution, saturated brine solution, dried over sodium sulphate and concentrated under reduced pressure to afford 62 mg (72.9% yield) of biphenyl-4-carboxylicacid {2-[4-(3-methyl-thiophene-2-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LC-MS purity: 90.22%, HPLC Purity: 92.38%, 1H NMR: (CDCl3) δ 7.9 (d, 2H), 7.75-7.6 (m, 4H), 7.5 (m, 2H), 7.4 (m, 1H), 7.3-7.4 (m, 2H), 6.9 (d, 1H), 4.3 (d, 2H), 3.7 (m, 6H), 3.5 (m, 2H), 2.4 (s, 3H).

1. extractionThe product was extracted with ethyl acetate
2. washthe ethyl acetate layer was washed with NaHCO3 solution, saturated brine solution
3. dry with materialdried over sodium sulphate
4. concentrationconcentrated under reduced pressure