Diisopropylethylamine → 4-(4-Benzyl-piperazin-1-yl)-1H-indole

HRID 1006414

Reaction equation

HRID 1006414 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([NH2:10])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Cl.[CH2:12]([N:19]([CH2:23][CH2:24]Cl)[CH2:20][CH2:21]Cl)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C>ClC1C=CC=CC=1>[CH2:12]([N:19]1[CH2:23][CH2:24][N:10]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH:3]=[CH:2][NH:1]3)[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 5834314-AminoindoleHCID 2777881N,N-Bis(2-chloroethyl)benzylamine hydrochloride

Product 1

HCID 27285324-(4-Benzyl-piperazin-1-yl)-1H-indoleYield 24.9%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 500 mg (3.78 mmole) 1H-indol-4-yl-amine, 993 mg (3.78 mmole) N-benzyl-bis(2-chloroethyl)amine hydrochloride, and 1.32 mL (7.6 mmole) diisopropylethylamine in 10 mL chlorobenzene was heated at 130° C. for 24 hours. Another 0.66 mL (3.8 mmole) diisopropylethylamine was added and the mixture was heated at 130° C. for an additional 5 hours. The mixture was partitioned between 25 mL ethyl acetate and 10 mL 5% sodium hydroxide. The organic phase was extracted with 10 mL 3 N hydrochloric acid. The aqueous phase was washed with 15 mL ethyl ether, then made basic with 50% sodium hydroxide. The product was extracted with 25 mL dichloromethane, the organic phase was washed with 10 mL water, dried (magnesium sulfate) and concentrated under reduced pressure. 4-(4-benzyl-piperazin-1-yl)-1H-indole (274 mg) was isolated as the hydrochloride salt from ethyl ether.

Workup

  1. temperaturethe mixture was heated at 130° C. for an additional 5 hours
  2. customThe mixture was partitioned between 25 mL ethyl acetate and 10 mL 5% sodium hydroxide
  3. extractionThe organic phase was extracted with 10 mL 3 N hydrochloric acid
  4. washThe aqueous phase was washed with 15 mL ethyl ether
  5. extractionThe product was extracted with 25 mL dichloromethane
  6. washthe organic phase was washed with 10 mL water
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9408847ab45a49e3b91921d8b0d4da6e
Source dataset
uspto-grants-2004_09
Patent number
US06790848B2

Linked notes

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