Pyridine → (6S,9aS)-N-Benzyl-8-((6-(3-((2S)-2,4-dimethylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-6-((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-8-((6-fluoropyridin-2-yl)methyl)-6-((4-hydroxyphenyl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide (3.68 g, 6.59 mmol) described in Production Example 2-4 and pyridine (20 mL) was added a mixture (4.45 g) of (2S)-1-(azetidin-3-yl)-2,4-dimethylpiperazine and benzylbenzene described in Production Example 6-3 at room temperature. The resultant mixture was stirred under reflux for 5 hours and 45 minutes. The reaction mixture was cooled to room temperature, and was then concentrated under a reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1 and subsequently methanol) and then further purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1) to give a solid material. Ethyl acetate, diethyl ether and heptane were added to the solid material, and a precipitate was collected by filtration to give the title compound (3.44 g, yield: 74%).

Provenance & Evidence