反应详情

To a mixture of 220 mg of methyl 4-[2-(4-{[(2-{[3-({[2-(methylamino)ethyl](pentan-3-yl)amino}methyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate, 0.20 mL of N-ethyl-N-isopropylpropan-2-amine and 5.0 mL of methylene chloride was added 100 mg of 2,2-dimethylglutaric anhydride under ice cooling, followed by stirring for 1 hour at the same temperature and then for a day at room temperature, and the reaction mixture was concentrated under reduced pressure. 200 mg of potassium carbonate and 10 mL of DMF were added to the obtained residue, 150 mg of methyl iodide was further added thereto under ice cooling, and the reaction mixture was stirred for 1 hour under ice cooling and then for a day at room temperature. Ethyl acetate and water were added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (5% methanol/chloroform), thereby obtaining 260 mg of methyl 4-(2-{4-[({2-[(3-{[{2-[(5-methoxy-4,4-dimethyl-5-oxopentanoyl)(methyl)amino]ethyl}(pentan-3-yl)amino]methyl}benzoyl)amino]-4,5,6,7-tetrahydro-1-benzothiophen-3-yl}carbonyl)amino]phenyl}ethyl)benzoate.

1. waitfor a day at room temperature
2. concentrationthe reaction mixture was concentrated under reduced pressure
3. addition200 mg of potassium carbonate and 10 mL of DMF were added to the obtained residue, 150 mg of methyl iodide
4. additionwas further added
5. stirringunder ice cooling, and the reaction mixture was stirred for 1 hour under ice cooling
6. waitfor a day at room temperature
7. additionEthyl acetate and water were added to the reaction mixture
8. extractionfollowed by extraction with ethyl acetate
9. washThe organic layer was washed with saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationfollowed by concentration under reduced pressure
12. customThe residue was purified by silica gel column chromatography (5% methanol/chloroform)