Hydrochloric Acid → 2-(5-chloro-1-(2-cyclopentylethyl)-1H-indol-3-yl)-N-methylethanamine

HRID 1775947Notes

Reaction equation

HRID 1775947 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:11][CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)N)=[CH:5][CH:4]=1.C(O[CH:21](OCC)[CH2:22][CH2:23][CH2:24][NH:25][CH3:26])C>C(O)C.O>[Cl:2][C:3]1[CH:8]=[C:7]2[C:6](=[CH:5][CH:4]=1)[N:9]([CH2:11][CH2:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)[CH:21]=[C:22]2[CH2:23][CH2:24][NH:25][CH3:26]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid3×HCID 139945474,4-Diethoxy-N-methylbutan-1-amine2×HCID 669116271-(4-Chlorophenyl)-1-(2-cyclopentylethyl)hydrazine

Product 1

HCID 669116392-(5-chloro-1-(2-cyclopentylethyl)-1H-indol-3-yl)-N-methylethanamineYield 56.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

28% aqueous HCl (0.3 mL, 2.26 mmol) was added to a solution of N-(4-Chloro-phenyl)-N-(2-cyclopentyl-ethyl)-hydrazine (0.54 g, 2.26 mmol) in ethanol (2.5 mL) and water (1 mL) under a nitrogen atmosphere. The reaction was heated to 60° C. (oil bath temperature) and 4,4-diethoxy-N-methylbutan-1-amine (0.32 g, 1.84 mmol) was added. The reaction was heated to reflux and 28% aqueous HCl (0.15 mL, 1.13 mmol) was added. The reaction was heated at reflux for 2.5 h. The reaction was cooled to 60° C. and then more 4,4-diethoxy-N-methylbutan-1-amine (0.32 g, 1.84 mmol) was added. The reaction was heated to reflux and then more 28% aqueous HCl (0.15 mL, 1.13 mmol) was added. The reaction was heated to reflux for a further 3.5 h. The reaction was cooled and concentrated under reduced pressure. The red brown residue was subjected to column chromatography (silica gel, eluent: EtOAc followed by EtOAc:EtOH:NH4OH 90:10:1) to give the product (0.318 g, 46%).

Workup

  1. additionwas added
  2. temperatureThe reaction was heated
  3. temperatureto reflux
  4. temperatureThe reaction was heated
  5. temperatureat reflux for 2.5 h
  6. temperatureThe reaction was heated
  7. temperatureto reflux
  8. temperatureThe reaction was heated
  9. temperatureto reflux for a further 3.5 h
  10. temperatureThe reaction was cooled
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-430e7cfe322e4ea588cdcdd964522648
Source dataset
uspto-grants-2016_02
Patent number
US09260429B2

Reaction notes

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