N,N'-Dimethylethylenediamine → Pyrazino[1,2-a]indol-1(2H)-one, 2-(3-bromo-2-methylphenyl)-3,4,6,7,8,9-hexahydro-

HRID 1918789Notes

Reaction equation

HRID 1918789 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:6]=[C:5]1[C:13]([O:15]CC)=O.[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](Br)[C:20]=1[CH3:26].C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>CNCCNC.[Cu].O1CCOCC1>[Br:18][C:19]1[C:20]([CH3:26])=[C:21]([N:1]2[CH2:2][CH2:3][N:4]3[C:12]4[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=4[CH:6]=[C:5]3[C:13]2=[O:15])[CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 346812,6-DibromotolueneHCID 58043965Ethyl 1-(2-Aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

Product 1

HCID 58043828Pyrazino[1,2-a]indol-1(2H)-one, 2-(3-bromo-2-methylphenyl)-3,4,6,7,8,9-hexahydro-Yield 57%

Reagents, catalysts & solvents 2

HCID 86661228HCID 86661228, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A 50-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with ethyl 1-(2-aminoethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate 101k (560 m g, 2.95 mmol), 2,6-dibromotoluene (1.47 g, cesium carbonate (1.92 g, 5.90 mmol), N,N′-dimethylethylenediamine (260 mg, 2.95 mmol) and 1,4-dioxane (25 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper N,N′-dimethylethylenediamine (260 mg, 2.95 mmol) was added, and the reaction mixture was heated at 105° C. (oil bath temperature) for 14 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (100 mL) and water (20 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 57% yield (600 mg) of 2-(3-bromo-2-methylphenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one 101l as a white solid: mp 163-165° C.; 1H NMR (500 MHz, DMSO-d6) d 7.57 (dd, 1H, J=8.0, 0.5 Hz), 7.32 (d, 1H, J=7.5 Hz), 7.21 (t, 1H, J=8.0 Hz), 6.50 (s, 1H), 4.11 (m, 3H), 3.75 (m, 1H), 2.59 (m, 2H), 2.45 (m, 2H), 2.21 (s, 3H), 1.78 (m, 2H), 1.68 (m, 2H); (APCI+) m/z 358.6 (M+H)

Workup

  1. customA 50-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet
  2. customAfter bubbling nitrogen through the resulting suspension for 30 min
  3. temperatureAfter this time, the mixture was cooled to room temperature
  4. filtrationfiltered
  5. additionThe filtrate was diluted with ethyl acetate (100 mL) and water (20 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×30 mL)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-8530e7114bba4f259bf5e744ed8b4125
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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