反应详情

温度

120 °C

4-Chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-3-quinolinecarboxamide (for a preparation see Intermediate 9) (3.33 g, 10.04 mmol) was dissolved in NMP (10 ml) and DIPEA (1.8 ml, 10 mmol) and [(1R)-1-phenylethyl]amine (1.58 g, 13.05 mmol) were added, then the solution was heated at 120° C. for 18 h, then cooled to room temperature, diluted with water (100 ml) and extracted with EtOAc (2×100 ml). The organic layer was washed with water (2×100 ml), dried with sodium sulphate and evaporated in vacuo to give a brown gum. This was dissolved in DCM 20 ml) and loaded onto a 100 g silica cartridge, then eluted with MeOH/DCM (0-10%) and product-containing fractions evaporated in vacuo to give 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-phenylethyl]amino}-3-quinolinecarboxamide (3.5 g, 8.40 mmol, 84% yield) as a beige solid. LCMS (formate) Rt 0.84 min, MH+ 417

1. temperaturecooled to room temperature
2. extractionextracted with EtOAc (2×100 ml)
3. washThe organic layer was washed with water (2×100 ml)
4. dry with materialdried with sodium sulphate
5. customevaporated in vacuo
6. customto give a brown gum
7. washeluted with MeOH/DCM (0-10%)
8. additionproduct-containing fractions
9. customevaporated in vacuo