反应详情

To a mixed solution of (6S,9aS)-N-benzyl-6-((2-fluoro-4-hydroxyphenyl)methyl)-8-((6-fluoropyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide (20.0 mg, 0.0347 mmol) described in Production Example 1-1-6 and NMP (2.0 mL) was added a mixture (59.0 mg) of (2R)-4-(azetidin-3-yl)-1,2-dimethylpiperazine and benzylbenzene described in Production Example 5-3 at room temperature. The resultant mixture was irradiated with a microwave at 140° C. for 12 hours. The reaction mixture was cooled to room temperature, and then water was added thereto, the resultant solution was extracted with ethyl acetate, and an organic layer was washed with water and then with saturated brine. An organic layer was dried over anhydrous magnesium sulfate and then filtrated. The solvent was evaporated under a reduced pressure, and the resultant residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1) and then further purified by NH silica gel thin-layer chromatography (ethyl acetate) to give the title compound (10.8 mg, yield: 43%).

1. customdescribed in Production Example 5-3 at room temperature
2. extractionthe resultant solution was extracted with ethyl acetate
3. washan organic layer was washed with water
4. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
5. filtrationfiltrated
6. customThe solvent was evaporated under a reduced pressure
7. customthe resultant residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1)
8. customfurther purified by NH silica gel thin-layer chromatography (ethyl acetate)