3-(2-Bromoethyl)indole → N-(3-{3-[2-(1H-Indol-3-yl)ethyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 1826374Notes

Reaction equation

HRID 1826374 reaction equation
[CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)[CH:7]2[CH:3]1[CH2:4][NH:5][CH2:6]2.C(=O)([O-])O.[Na+].Br[CH2:25][CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1>CN(C)C=O>[NH:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:27]([CH2:26][CH2:25][N:5]2[CH2:6][CH:7]3[CH:3]([C:2]3([C:8]3[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=3)[CH3:1])[CH2:4]2)=[CH:28]1

Participants

5

Reactant 3

HCID 769243-(2-Bromoethyl)indoleHCID 516892Sodium BicarbonateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 1

HCID 9909452N-(3-{3-[2-(1H-Indol-3-yl)ethyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 50 mg, 0.165 mmol) in N,N-dimethylformamide (2 ml) was added sodium hydrogen carbonate (35 mg, 0.413 mmol) and 3-(2-bromoethyl)indole (37 mg, 0.165 mmol). The reaction mixture was heated at 55° C. for 48 h, cooled to room temperature and concentrated in vacuo. Water (10 ml) was added and the product was extracted with ethyl acetate (3×10 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to give a brown oil. The crude product was purified by chromatography using a Biotage Flash 12™ cartridge packed with silica gel (8 g), eluting with hexane:ethyl acetate (100:0 and then 0:100). The title compound was obtained as a glass (22 mg, 33%).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. additionWater (10 ml) was added
  4. extractionthe product was extracted with ethyl acetate (3×10 ml)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil
  9. customThe crude product was purified by chromatography
  10. washeluting with hexane:ethyl acetate (100:0

Sources & evidence

ORD record
ord-da2806bb7ba94f1096e4d93e889d2cff
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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