Cesium carbonate → HCID 67986827, compound

HRID 2365420Notes

Reaction equation

HRID 2365420 reaction equation
[F: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[C:31]([CH3:33])([CH3:32])[N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29][CH2:28][C:23]=3[N:24]([CH3:27])[C:25]=2[CH:26]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I>[F: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[C:31]([CH3:32])([CH3:33])[N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[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

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 575147614-(4-Fluorophenethyl)piperazin-2-oneHCID 67969542HCID 67969542, compound

Product 1

HCID 67986827HCID 67986827, compoundYield 66.1%

Reagents, catalysts & solvents 2

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

Procedure

A suspension of 4-(4-fluorophenethyl)piperazin-2-one (66.6 mg, 0.300 mmol), tert-butyl 7-bromo-1,1,5-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (120 mg, 0.300 mmol), CuI (114 mg, 0.600 mmol), (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (95.0 μL, 0.600 mmol) and Cs2CO3 (195 mg, 0.600 mmol) in dioxane (5.00 mL) was degassed under reduced pressure for 5 min. The suspension was put under N2 and stirred at refluxing temperature for 24 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added, and the resulting suspension was stirred at 25° C. for 20 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine (3×). The resulting solution was dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by flash chromatography (silica gel, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 50:50) afforded the title compound (106 mg, 66%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 7.59 (d, J=8.5 Hz, 1H), 7.21-7.17 (m, 3H), 7.02-6.95 (m, 3H), 3.85 (t, J=5.0 Hz, 2H), 3.75 (t, J=5.0 Hz, 2H), 3.60 (s, 3H), 3.43 (s, 2H), 2.91-2.88 (m, 2H), 2.86-2.82 (m, 2H), 2.78-2.70 (m, 4H), 1.85 (s, 6H), 1.55-1.53 (m, 9H).

Workup

  1. customwas degassed under reduced pressure for 5 min
  2. temperatureat refluxing temperature for 24 h
  3. temperatureThe suspension was cooled
  4. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH was added
  5. stirringthe resulting suspension was stirred at 25° C. for 20 min
  6. washthe filtrate was washed with brine (3×)
  7. dry with materialThe resulting solution was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography (silica gel, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 50:50)

Sources & evidence

ORD record
ord-d50211db4cd0450ea118fc67b22dea04
Source dataset
uspto-grants-2014_04
Patent number
US08697700B2

Reaction notes

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