3-(2-(4-Pyridyl)ethyl)indole → 1-butyl-N,N-dimethyl-4,4-bis(3-(2-(pyridin-4-yl)ethyl)-1H-indol-2-yl)cyclohexanamine

HRID 1011629Notes

Reaction equation

HRID 1011629 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][CH:10]=2)=[CH:3][CH:2]=1.[CH2:18]([C:22]1([N:29]([CH3:31])[CH3:30])[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21].FC(F)(F)S(O)(=O)=O>ClCCl>[CH2:18]([C:22]1([N:29]([CH3:31])[CH3:30])[CH2:27][CH2:26][C:25]([C:10]2[NH:11][C:12]3[C:17]([C:9]=2[CH2:8][CH2:7][C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)([C:10]2[NH:11][C:12]3[C:17]([C:9]=2[CH2:8][CH2:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21]

Participants

5

Reactant 3

HCID 279343-(2-(4-Pyridyl)ethyl)indoleHCID 62406Trifluoromethanesulfonic acidHCID 57475098HCID 57475098, compound

Product 1

HCID 445131681-butyl-N,N-dimethyl-4,4-bis(3-(2-(pyridin-4-yl)ethyl)-1H-indol-2-yl)cyclohexanamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(2-pyridin-4-ylethyl)-1H-indole (667 mg, 3 mmol, synthesis cf. WO2008009415, indole unit Ind-14) together with 4-butyl-4-(dimethylamino)cyclohexanone (592 mg, 3 mmol, synthesis cf. WO2008009415, ketone unit Ket-4) was dissolved in dichloromethane (45 ml) and mixed with trifluoromethane sulphonic acid (0.553 ml, 6.3 mmol). The batch was stirred for 67 h at RT, and a brown oil separated out. For work up the reaction solution was mixed with 1N NaOH (10 ml) and THF (10 ml). The mixture was stirred a further 60 min. After separation of the phases the aqueous phase was extracted with dichloromethane (3×10 ml). The combined organic extracts were dried over Na2SO4 and then concentrated to low volume. The raw product obtained (1.24 g) was purified by column chromatography [silica gel 60 (100 g); ethyl acetate/methanol (10:1, 1200 ml), ethyl acetate/methanol (5:1, 600 ml) ethyl acetate/methanol (2:1, 700 ml), ethyl acetate/methanol (1:2, 750 ml), methanol (800 ml)].

Workup

  1. customa brown oil separated out
  2. additionFor work up the reaction solution was mixed with 1N NaOH (10 ml) and THF (10 ml)
  3. stirringThe mixture was stirred a further 60 min
  4. customAfter separation of the phases the aqueous phase
  5. extractionwas extracted with dichloromethane (3×10 ml)
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. concentrationconcentrated to low volume

Sources & evidence

ORD record
ord-14e392e6b7f34b05823996612c441abc
Source dataset
uspto-grants-2011_07
Patent number
US07977370B2

Reaction notes

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