Реакция #44939

Уравнение реакции

indomethacin

4-hydroxybutylamine

HOBt

DIPEA

EDCl

→

N-(4-hydroxybutyl)-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide

Выход 70.0%

Растворители

DMF

Условия реакции

Обработка

1. 1
   ДругоеRemoval of solvent in vacuo
2. 2
   Другоеafforded a residue, where 100 mL water
3. 3
   workup.ADDITIONwas added
4. 4
   Экстракцияextracted with EtOAc (3×75 mL)
5. 5
   СушкаCombined organic layers were dried over Na2SO4
6. 6
   ДругоеSolvent was evaporated completely
7. 7
   workup.DISSOLUTIONthe obtained mass was dissolved in CH2Cl2 (40 mL)
8. 8
   ДругоеHCl (gas) was bubbled for 2 h at 25° C
9. 9
   ДругоеRemoval of solvent in vacuo
10. 10
    Другоеafforded a yellow residue, where n-hexane
11. 11
    workup.ADDITIONwas added (20 mL)
12. 12
    Фильтрацияwas filtered

Методика

To a stirred solution of indomethacin (3.57 g, 10 mmol) in DMF was added 4-hydroxybutylamine (4.64 g), HOBt (2.02 g, 15 mmol), DIPEA (3.88 g, 30 mmol), EDCl (2.10 g, 11 mmol) at 25° C. The resultant solution was stirred for 16 h at 25° C. Removal of solvent in vacuo afforded a residue, where 100 mL water was added and extracted with EtOAc (3×75 mL). Combined organic layers were dried over Na2SO4. Solvent was evaporated completely and the obtained mass was dissolved in CH2Cl2 (40 mL), then HCl (gas) was bubbled for 2 h at 25° C. Removal of solvent in vacuo afforded a yellow residue, where n-hexane was added (20 mL) and stirred for 30 min to a make good slurry, which was filtered to afford the desired N-(4-hydroxybutyl)-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide as yellow solid (2.5 g, 70%). 1H NMR (500 MHz, DMSO-d6) δ 1.44-1.52 (m, 2H, CCH2CC), 1.53-1.59 (m, 2H, CCCH2C), 2.23 (s, 3H, CH3), 3.03-3.08 (m, 2H, CH2CCC), 3.52 (s, 2H, CH2CO), 3.75 (s, 3H, OCH3), 3.77-3.78 (m, 2H, CCCCH2), 4.53 (br s, 1H, OH), 6.684 (dd, J=9, 2.4 Hz, 1H, indolyl H-6), 6.916 (d, J=9 Hz, 1H, indolyl H-7), 7.144 (d, J=2.4 Hz, 1H, indolyl H-4), 7.64 (d, J=8.7 Hz, 2H, p-chlorobenzoyl H-3, H-5), 7.67 (d, J=8.7 Hz, 2H, p-chlorobenzoyl H-2, H-6), 8.24 (br s, 1H, NHCO). Mass (ESI) (M+Na) calcd for C23H25ClN2O4Na 451.15; found 451.04.

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