Sodium Iodide → 7-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroisoquinolin-1(2H)-one

HRID 1750089노트

반응식

HRID 1750089 반응식
Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][NH:13][C:14]2=[O:17])=[CH:9][CH:8]=1.[Na+].[I-].[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[N:28]1[CH2:34][CH2:33][CH2:32][N:31](CCCCOC2C=C3C(CCC(=O)N3)=CC=2)[CH2:30][CH2:29]1.C([O-])([O-])=O.[K+].[K+]>CC#N.O>[Cl:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[N:28]1[CH2:34][CH2:33][CH2:32][N:31]([CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:16]=[C:15]3[C:10]([CH2:11][CH2:12][NH:13][C:14]3=[O:17])=[CH:9][CH:8]=2)[CH2:30][CH2:29]1

참가 물질

7

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 56597938Unc0006HCID 686269787-(4-Bromobutoxy)-3,4-dihydro-1(2h)-isoquinolinone

생성물 1

HCID 565982107-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroisoquinolin-1(2H)-one수율 68.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

A mixture of intermediate 21 (100 mg, 0.34 mmol) and NaI (102 mg, 0.68 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 2 (144 mg, 0.51 mmol) and anhydrous K2CO3 (188 mg, 1.36 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-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydroisoquinolin-1(2H)-one (compound 6) (107 mg, 68%). 1H NMR (300 MHz, CDCl3) δ 7.58 (s, 1H), 7.20-7.09 (m, 3H), 7.02-6.98 (m, 2H), 6.04 (br., 1H), 4.05 (t, J=6.6 Hz, 2H), 3.54-3.52 (m, 2H), 3.32-3.28 (m, 4H), 2.95-2.91 (m, 6H), 2.70-2.68 (m, 2H), 2.06-2.04 (m, 2H), 1.84-1.77 (m, 4H). HPLC: 99%, RT 2.676 min. MS (ESI) m/z 462.4 [M+H]+. mp: 86-88° C.

후처리

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. extractionextracted with EtOAc
  6. washThe combined EtOAc layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1)

출처 및 근거

ORD 기록
ord-05842c3cb429463ea1937217a58b3f03
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156822B2

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