反应详情

Methanesulfonyl chloride (0.065 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (0.27 g) from Preparation No. 10, DMAP (0.017 g), and 2,4,6-collidine (0.12 mL) in anhydrous DMF (14 mL). The mixture is stirred at room temperature overnight and 2-(methylamino)ethanol (0.61 mL) is added. The reaction mixture is stirred at room temperature for 2 h, poured into water, and extracted with CH2Cl2 (3×). The organic layers are combined, dried (Na2SO4), filtered, and concentrated in vacuo. The residue is dissolved in CH2Cl2/MeOH and adsorbed onto silica. Purification by chromatography (eluent CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), 2.5% MeOH/CH2Cl2 (1 L), 3.5% MeOH/CH2Cl2 (1 L), 5% MeOH/CH2Cl2 (1 L), 6% MeOH/CH2Cl2 (1 L)) affords the product as a clear residue. The residue is crystallized by addition of CH2Cl2/hexanes followed by removal of the solvents in vacuo to give 0.21 g (69%) of the title compound as a white solid.

1. stirringThe reaction mixture is stirred at room temperature for 2 h
2. extractionextracted with CH2Cl2 (3×)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThe residue is dissolved in CH2Cl2/MeOH
7. customPurification by chromatography (eluent CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), 2.5% MeOH/CH2Cl2 (1 L), 3.5% MeOH/CH2Cl2 (1 L), 5% MeOH/CH2Cl2 (1 L), 6% MeOH/CH2Cl2 (1 L))
8. customaffords the product as a clear residue
9. customThe residue is crystallized by addition of CH2Cl2/hexanes
10. customfollowed by removal of the solvents in vacuo