反应详情

A suspension of 4-oxo-N-[(3-piperazin-1-ylphenyl)methyl]-3,4-dihydroquinazoline-2-carboxamide dihydrochloride obtained in Reference Example 116 (0.109 g, 0.250 mmol), (2,5-dioxoimidazolidin-4-yl)acetic acid (0.047 g, 0.300 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl-carbodiimide hydrochloride (0.096 g, 0.500 mmol) and 1-hydroxybenzotriazole (0.068 g, 0.500 mmol) in DMF (5 mL) was stirred at room temperature for 1 hr. Triethylamine (0.139 mL, 1.00 mmol) was added thereto, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase: distilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid), gradient: distilled water/acetonitrile=90/100/100, time: 10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and crystallized from methanol-diethyl ether to give the title compound as a pale-yellow powder (0.078 g, 62%).

1. stirringthe mixture was stirred at room temperature for 12 hr
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customthe residue was purified by preparative HPLC (GILSON 215LIQUD HANDLER, 322PUMP, UV/VIS-156, SHISEIDO CAPCELL PACK C-18 UG120 S-5 (20 mmφ×50 mm), mobile phase
4. distillationdistilled water (containing 0.1% trifluoroacetic acid)/acetonitrile (containing 0.1% trifluoroacetic acid)
5. distillationgradient: distilled water/acetonitrile=90/100/100, time
6. custom10 min, flow rate: 25 mL/min, detection wavelength: 220 nm), and crystallized from methanol-diethyl ether