1,4-Dioxane → HCID 22053589, compound

Participants

Reaction Steps

1-(t-butoxycarbonyl)homopiperazine (36.1 mg), diisopropylethylamine (0.1 mL) and 1,4-dioxane (1 mL) were added to 6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-2-(methylsulfonyl)-5-oxopyrimido[4,5-b][1,5]diazocine (Compound of Reference Example 19; 85.9 mg). While heated, the mixture was refluxed for 5 hours. The reaction mixture was then diluted with ethyl acetate, was washed with water, and was then dried over anhydrous sodium sulfate. The solvent was removed and 3 mol/L hydrogen chloride/ethyl acetate (1 mL) was added while the residue was chilled on an ice bath. The mixture was stirred for 30 min and then additional 1 hour at room temperature. Following removal of the solvent, the residue was dissolved in tetrahydrofuran (1 mL). While the residue was chilled on an ice bath, triethylamine (0.1 mL) and anhydrous acetic acid (0.05 mL) were added and the mixture was stirred at room temperature for 30 min. Subsequently, the reaction mixture was diluted with ethyl acetate, was washed with water, and was then dried over anhydrous sodium sulfate. Following removal of the solvent, the residue was purified on a silica gel column chromatography (ethyl acetate:methanol=10:1) to obtain 2-(4-acetylhomopiperazine-1-yl)-6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-5-oxopyrimido[4,5-b][1,5]diazocine (70.7 mg, 74%).

Provenance & Evidence