Hydrochloric Acid → 2-(5-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)-1-(4-methylpiperidin-1-yl)ethanone

HRID 2198334Notes

Reaction equation

HRID 2198334 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:10][C:11]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]2C)=[O:12])N)=[CH:4][CH:3]=1.Cl.C(O[CH:24](OCC)[CH2:25][CH2:26][CH2:27][NH:28][CH3:29])C.[CH3:33]COC(C)=O.CCO.[NH4+].[OH-]>C(OCC)(=O)C.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[N:8]([CH2:10][C:11]([N:13]1[CH2:14][CH2:15][CH:16]([CH3:33])[CH2:17][CH2:18]1)=[O:12])[CH:24]=[C:25]2[CH2:26][CH2:27][NH:28][CH3:29]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid3×HCID 139945474,4-Diethoxy-N-methylbutan-1-amine3×HCID 18433202Ethyl acetate ethanol ammonium hydroxideHCID 669117252-[N-(4-Chloro-phenyl)-hydrazino]-1-(methyl-piperidin-1-yl)-ethanone

Product 1

HCID 669116502-(5-chloro-3-(2-(methylamino)ethyl)-1H-indol-1-yl)-1-(4-methylpiperidin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

2-[N-(4-Chloro-phenyl)-hydrazino]-1-(methyl-piperidin-1-yl)-ethanone (0.75 g, 2.66 mmol) was dissolved in ethyl acetate (3 mL) and 4M hydrochloride in dioxane (0.7 mL) was added. The mixture was concentrated under reduced pressure to a glassy oil/foam. This was dissolved in a mixture of ethanol (4 mL) and water (2 mL) and heated to 60° C. The 4,4-diethoxy-N-methylbutan-1-amine (0.47 g, 2.68 mmol) was added and then heated to 7080° C. 28% aqueous HCl (0.35 mL, 2.66 mmol) was added and the reaction heated at 80° C. for 1 h. More 4,4-diethoxy-N-methylbutan-1-amine (0.2 g, 1.14 mmol) and 28% aqueous HCl (0.3 mL, 2.30 mmol) was added and heated for a further 3 h. Further 4,4-diethoxy-N-methylbutan-1-amine (0.3 g, 1.71 mmol) was added and heated for a further 6 h. The reaction was concentrated under reduced pressure to give a dark brown oil. The oil was subjected to column chromatography (silica gel, eluent: EtOAc:EtOH:NH4OH 7:3:1) to give a brown oil (0.29 g). Further purification of the brown oil by column chromatography (silica gel, eluent: EtOAc:EtOH:NH4OH 7:3:1) gave pure product (179 mg, 19%).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure to a glassy oil/foam
  2. dissolutionThis was dissolved in a mixture of ethanol (4 mL) and water (2 mL)
  3. temperatureheated to 7080° C
  4. temperaturethe reaction heated at 80° C. for 1 h
  5. temperatureheated for a further 3 h
  6. temperatureheated for a further 6 h
  7. concentrationThe reaction was concentrated under reduced pressure
  8. customto give a dark brown oil

Sources & evidence

ORD record
ord-a3f7cac158a34fbe86db44750993fe27
Source dataset
uspto-grants-2012_12
Patent number
US08338447B2

Reaction notes

Loading…