Trimethylsilyl iodide → HCID 11563152, compound

Participants

Reaction Steps

Methyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}pyridin-2-yl)oxy]-2,2-dimethylbutanoate was prepared from (2S,4R)-N-(4-chloro-phenyl)-N-[1-(6-methoxy-pyridine-3-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide by deprotection of the methoxy and elaboration. (2S,4R)-N-(4-chloro-phenyl)-N-[1-(6-methoxy-pyridine-3-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.062 g, 0.13 mmol) was dissolved in methylene chloride and TMSI (0.020 mL, 0.13 mmol) was added and stirred at room temperature for 14 h. The reaction mixture was concentrated down and methanol was added and stirring was continued for 10 h, concentrated down and used directly. N-(4-chlorophenyl)-N-{(2S,4R)-1-[(6-hydroxypyridin-3-yl)carbonyl]-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl}acetamide (0.060 g, 0.13 mmol) was dissolved in 2 mL of dimethylformamide, followed by 0.046 g of methyl 4-bromo-2,2-dimethylbutanoate (0.20 mmol) and 0.057 g of silver carbonate (0.20 mmol). The flask was covered with aluminum foil and the lights were turned off in the enclosure. The reaction was allowed to heat to 80° C. for 24 h. Additional methyl 4-bromo-2,2-dimethylbutanoate (0.046 g, 0.20 mmol) was added and continued stirring at 80° C. for 24 h. The reaction was concentrated down and partitioned between ethyl acetate and water. The organics were collected together and dried over MgSO4, filtered and concentrated. The residue was purified with 2% methanol/98% methylene chloride to 5% methanol/95% methylene chloride to 10% methanol/90% methylene chloride. Two products were obtained the O- and N-alkylated product, methyl 4-[(5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}pyridin-2-yl)oxy]-2,2-dimethylbutanoate (0.025 g, 32%) and methyl 4-[5-{[(2S,4R)-4-[acetyl(4-chlorophenyl)amino]-2-methyl-3,4-dihydroquinolin-1(2H)-yl]carbonyl}-2-oxopyridin-1(2H)-yl]-2,2-dimethylbutanoate (0.025 g, 32%).

Provenance & Evidence