Phenethyl bromide → Avn-101

HRID 2195829

Reaction equation

HRID 2195829 reaction equation
Cl.[C:2]1([CH3:10])[CH:7]=[CH:6][C:5]([NH:8]N)=[CH:4][CH:3]=1.[C:11]1([CH2:17][CH2:18]Br)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C.Cl.[CH3:28][N:29]1[CH2:34][CH2:33][C:32](=O)[CH2:31][CH2:30]1>C(O)C>[CH3:28][N:29]1[CH2:34][CH2:33][C:32]2[N:8]([CH2:18][CH2:17][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:5]3[CH:4]=[CH:3][C:2]([CH3:10])=[CH:7][C:6]=3[C:31]=2[CH2:30]1

Participants

6

Reactant 4

HCID 7666Phenethyl bromideHCID 8471TriethylamineHCID 125044-Methylphenylhydrazine monohydrochlorideHCID 122100571-Methylpiperidin-4-one hydrochloride

Product 1

HCID 42631003Avn-101Yield 3.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Preparation of the title compound was carried out according to General Method 8. p-Tolylhydrazine hydrochloride (2 g, 12.6 mmol), 2-phenyl ethyl bromide (1.7 ml, 12.6 mmol) and triethyl amine (1.7 mL, 12.6 mmol) in ethanol (6 ml) were stirred at 25° C. for 1 h after which the contents were heated at 80° C. for 2 h. The contents were cooled to 25° C., N-methyl-4-piperidone hydrochloride (2.87 g, 18.9 mmol) was added and heating was continued at 80° C. for 16 h. The contents were concentrated in vacuo, basified by adding saturated aqueous NaHCO3, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel chromatography (230-400 mesh) using ethyl acetate-hexane gradient to obtain 150 mg of 2,3,4,5-tetrahydro-2,8-dimethyl-5-phenethyl-1H-pyrido[4,3-b]indole. The free base was converted into its oxalate salt by treatment of oxalic acid (1 equiv) in anhydrous THF.

Workup

  1. temperatureThe contents were cooled to 25° C.
  2. temperatureheating
  3. concentrationThe contents were concentrated in vacuo
  4. additionby adding saturated aqueous NaHCO3
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography (230-400 mesh)

Sources & evidence

ORD record
ord-6639b69c60d54942a85a8fbf1de1c9f3
Source dataset
uspto-grants-2012_12
Patent number
US08338408B2

Linked notes

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