反应详情

温度

80 °C

Sodium hydride (72 mg, 3 mmol) is added to a solution of 7-chloro-4-quinolone (359 mg, 2 mmol) in DMF. After 1 h at 40° C. N-phenyl(trifluoromethylsulfon)imide (1.0 g, 2.8 mmol) and, 1 h later, 1-tert-butoxycarbonyl-2,5-dimethylpiperazine (1.8 g, 8 mmol) is added. The reaction mixture is stirred at 80° C. for 2 days, concentrated, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and concentrated. The residue is purified by reversed phase HPLC with water-MeCN-TFA to give 4-[4-(tert-butoxycarbonyl)-2,5-dimethylpiperazin-1-yl]-7-chloroquinoline (188 mg, 0.5 mmol) which is deprotected with TFA in CH2Cl2 and transformed after being washed with base into the product with 4-fluorophenyl isocyanate (31 μL, 0.27 mmol) according to method C giving the title product as a colorless solid.

1. concentrationconcentrated
2. additiondiluted with EtOAc
3. washwashed with water and brine
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated
6. customThe residue is purified by reversed phase HPLC with water-MeCN-TFA