Cesium carbonate → tert-butyl 8-(4-(4-chlorophenethyl)-2-oxopiperazin-1-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

HRID 474941

반응식

HRID 474941 반응식
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]2)=[CH:4][CH:3]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28][C:23]=3[N:24]([CH3:27])[C:25]=2[CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN[C@@H]1CCCC[C@H]1NC>O1CCOCC1.[Cu]I>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:18]3[CH:19]=[CH:20][C:21]4[C:22]5[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28][C:23]=5[N:24]([CH3:27])[C:25]=4[CH:26]=3)[C:10](=[O:14])[CH2:9]2)=[CH:15][CH:16]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 580922294-(4-Chlorophenethyl)piperazin-2-oneHCID 58093439tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

생성물 1

HCID 66873906tert-butyl 8-(4-(4-chlorophenethyl)-2-oxopiperazin-1-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 312751,4-Dioxane용매

반응 조건

온도
25 °C

실험 절차

A suspension of 4-(4-chlorophenethyl)piperazin-2-one (90 mg, 0.38 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (130 mg, 0.344 mmol), Cs2CO3 (123 mg, 0.378 mmol), CuI (131 mg, 0.688 mmol) and trans-1,2-bis(methylamino)cyclohexane (24 mg, 0.17 mmol) in dioxane (10 mL) was degassed by bubbling N2 through the suspension for 45 min. The suspension was put under N2 and heated at reflux for 5 d. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. Activated carbon was added to the resulting solution, and the resulting suspension was filtered. The filtrate was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH) afforded tert-butyl 8-(4-(4-chlorophenethyl)-2-oxopiperazin-1-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate as a tan solid. 2 N HCl in Et2O (100 mL) was added to a solution of the tan solid in CH2Cl2 (5 mL) under N2, and the resulting suspension was stirred at 25° C. for 16 h. The suspension was concentrated, and the resulting residue was dissolved in MeOH (1 mL). Et2O (100 mL) was added, the resulting suspension was filtered, and the solid was washed with Et2O and put in a vacuum oven at 40° C. for 1 h to afford 22 mg (13%) of the title compound as a tan solid: 1H NMR (500 MHz, DMSO-d6) δ 11.54 (br s, 1H), 9.16 (br s, 2H), 7.54-7.32 (m, 6H), 6.96 (d, J=8.0 Hz, 1H), 4.21-3.44 (m, 9H), 3.42-3.05 (m, 12H); ESI MS m/z 437 [M+H]+.

후처리

  1. customwas degassed
  2. customby bubbling N2 through the suspension for 45 min
  3. temperatureheated
  4. temperatureat reflux for 5 d
  5. temperatureThe suspension was cooled
  6. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added
  7. washthe filtrate was washed with brine
  8. additionActivated carbon was added to the resulting solution
  9. filtrationthe resulting suspension was filtered
  10. dry with materialThe filtrate was dried over Na2SO4
  11. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-ffa85fe0a81245b9a8a729eb9086bce9
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637501B2

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