Sulfuric Acid → 2,3,4,5-Tetrahydro-8-iodo-2-methyl-1h-pyrido[4,3-b]indole

HRID 1400338Notes

Reaction equation

HRID 1400338 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]N)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH3:15][N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>O1CCOCC1>[I:1][C:2]1[CH:7]=[CH:6][C:5]2[NH:8][C:19]3[CH2:20][CH2:21][N:16]([CH3:15])[CH2:17][C:18]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 740491-Methyl-4-piperidoneHCID 7045914-Iodophenylhydrazine

Product 1

HCID 594549742,3,4,5-Tetrahydro-8-iodo-2-methyl-1h-pyrido[4,3-b]indole

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of compound 4-iodophenylhydrazine (1 equiv.) in 1,4-dioxane (50 mL) is added conc. sulfuric acid, followed by dropwise addition of 1-methyl-4-piperidone (1 equiv.) at RT. The reaction mixture is heated at 70° C. for 90 min., evaporated, diluted with water and the pH is adjusted to 12 with 40 mL of 15% aq. KOH solution. The reaction mixture is extracted with EtOAc, followed by brine wash, dried over sodium sulfate and evaporated under vacuum. The crude product is column purified over 230-400 silica gel using a gradient of 0-5% of MeOH in EtOAc. Note 1: The reaction temperature should be 70° C. Higher temperature results in the de-iodo carboline.

Workup

  1. customevaporated
  2. additiondiluted with water
  3. extractionThe reaction mixture is extracted with EtOAc
  4. washwash
  5. dry with materialdried over sodium sulfate
  6. customevaporated under vacuum
  7. custompurified over 230-400 silica gel using a gradient of 0-5% of MeOH in EtOAc
  8. customshould be 70° C
  9. customHigher temperature results in the de-iodo carboline

Sources & evidence

ORD record
ord-c67ab966e05d48daaea7d3942a6858a7
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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