Methyl iodide → 2-Chloro-7,7-difluoro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

関与物質

反応条件

反応手順

2-chloro-7,7-difluoro-9-isopropyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (0.800 g, 2.89 mmol) was dissolved in DMA (7 mL) and cooled to 0° C. under nitrogen. NaH (140 mg, 3.50 mmol) was added, the mixture was stirred for 20 min and MeI (0.23 mL, 3.61 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 h and quenched with water (25 mL). The pH was adjusted to 1 (aq. HCl) and the mixture was extracted with ethyl acetate (4×20 mL). The comb organic extracts were concentrated in vacuo, dissolved in dichloromethane/trifluoroacetic acid (5:1, 6 ml) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (80 g SiO2, hexanes:ethyl acetate 1:1) to afford the title compound as a yellow solid (0.753 g, 90%).

情報源と証拠