반응 #1837269

반응 방정식

intermediate 20

7-(3-bromopropoxy)-3,4-dihydroisoquinolin-1(2H)-one

NaI

Intermediate 2

7-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one

K2CO3

→

7-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)-3,4-dihydroisoquinolin-1(2H)-one

수율 71.5%

용매

CH3CN

water

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도to reflux for 30 min
3. 3
   온도The resulting mixture was heated
4. 4
   온도to reflux
5. 5
   추출extracted with EtOAc
6. 6
   세척The combined EtOAc layers were washed with brine
7. 7
   건조dried over anhydrous Na2SO4
8. 8
   농축concentrated in vacuo
9. 9
   기타purified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1)

실험 절차

A mixture of intermediate 20 (110 mg, 0.39 mmol) and NaI (117 mg, 0.78 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (165 mg, 0.58 mmol) and anhydrous K2CO3 (216 mg, 1.56 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred overnight. The reaction solution was diluted with water and extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1) to give 7-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)-3,4-dihydroisoquinolin-1(2H)-one (compound 5) (125 mg, 71%). 1H NMR (300 MHz, CDCl3) δ 7.60 (d, J=2.1 Hz, 1H), 7.14-7.08 (m, 3H), 7.02-7.00 (m, 2H), 6.02 (br., 1H), 4.10 (t, J=6.3 Hz, 2H), 3.56-3.53 (m, 2H), 3.31-3.27 (m, 4H), 2.96-2.88 (m, 6H), 2.77-2.72 (m, 2H), 2.01 (m, 4H). HPLC: 99%, RT 2.578 min. MS (ESI) m/z 448.1 [M+H]+. mp: 116-117° C.

출처