Cesium carbonate → tert-Butyl 9-methyl-7-(2-oxo-4-phenethylpiperazin-1-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

HRID 2365387Notes

Reaction equation

HRID 2365387 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:7]=3[N:8]2[CH3:11])=[CH:4][CH:3]=1.[CH2:23]([N:31]1[CH2:36][CH2:35][NH:34][C:33](=[O:37])[CH2:32]1)[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)Cl.CO.[NH4+].[OH-].[Cu]I>[CH3:11][N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([N:34]3[CH2:35][CH2:36][N:31]([CH2:23][CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:32][C:33]3=[O:37])[CH:10]=2)[C:6]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:7]1=2

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 85471654-Phenethylpiperazin-2-oneHCID 57950468tert-butyl 7-bromo-9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate

Product 1

HCID 67986813tert-Butyl 9-methyl-7-(2-oxo-4-phenethylpiperazin-1-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylateYield 10%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 21896990Dichloromethane methanol ammonium hydroxideSolvent

Conditions

Temperature
110 °C

Procedure

tert-Butyl 7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (270 mg, 0.740 mmol), 4-phenethylpiperazin-2-one (150 mg, 0.735 mmol), CuI (140 mg, 0.735 mmol), trans-N,N′dimethylcyclohexane-1,2-diamine (104 mg, 0.735 mmol) and Cs2CO3 (311 mg, 0.956 mmol) in toluene (15 mL) were sparged with a nitrogen stream for 45 min and then stirred at 110° C. for 16 h. The mixture was diluted with 90:9:1 CH2Cl2/MeOH/NH4OH (50 mL) and washed with brine (3×50 mL). The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride and a 9:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 85% methylene chloride, to provide the title compound (35 mg, 10%) as a yellow oil: ESI MS m/z 489 [M+H]+.

Workup

  1. washwashed with brine (3×50 mL)
  2. dry with materialThe resulting solution was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride

Sources & evidence

ORD record
ord-885fcb4022344bffb16ee49e467d48b7
Source dataset
uspto-grants-2014_04
Patent number
US08697700B2

Reaction notes

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