(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 → (6S,9aS)-N-Benzyl-8-((6-(3-((3S)-3,4-dimethylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-6-((2-fluoro-4-hydroxyphenyl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide

Participants

Reaction Steps

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 (4.00 g 6.94 mmol) described in Production Example 1-1-6 and pyridine (100 mL) was added (2S)-4-(azetidin-3-yl)-1,2-dimethylpiperazine (2.35 g, 13.9 mmol) described in Production Example 4-3 at room temperature. The resultant mixture was stirred under reflux for 6 hours and 50 minutes. The reaction mixture was cooled to room temperature, and then concentrated under a reduced pressure. The resultant residue was purified by silica gel column chromatography (methanol), and then purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1) to give the title compound (2.93 g, yield: 58%).

Provenance & Evidence