Pyridine → N-[1-Isopropyl-3-(3,4,5-trifluoro-phenyl)-1H-indol-6-yl]-methanesulfonamide

HRID 2079885Notes

Reaction equation

HRID 2079885 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:14]3[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]([F:22])[CH:15]=3)=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[CH:4][CH:3]=1.ClCCl.N1C=CC=CC=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>C(OCC)(=O)C>[CH:11]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([NH:1][S:33]([CH3:32])(=[O:35])=[O:34])[CH:10]=2)[C:6]([C:14]2[CH:19]=[C:18]([F:20])[C:17]([F:21])=[C:16]([F:22])[CH:15]=2)=[CH:7]1)([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 31297Methanesulfonyl chlorideHCID 574421936-amino-1-isopropyl-3-(3,4,5-trifluoro-phenyl)-1H-indole

Product 1

HCID 67101228N-[1-Isopropyl-3-(3,4,5-trifluoro-phenyl)-1H-indol-6-yl]-methanesulfonamideYield 65.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Method I Combine 6-amino-1-isopropyl-3-(3,4,5-trifluoro-phenyl)-1H-indole (116.6 mg, 0.38 mmol), prepared as described immediately above, dichloromethane (3.0 mL) and pyridine (62 μL, 0.76 mmol) under a nitrogen atmosphere in a 25 mL flask. Cool the reaction to 0° C. and add methane sulfonyl chloride (33 μL, 0.42 mmol). Allow the reaction to warm to RT while stirring for 3 hours. Quench reaction with saturated aqueous sodium bicarbonate (5 mL), dilute with ethyl acetate (10 mL) and separate the layers. Wash the organic layer with water (5 mL), brine (5 mL), dry (Na2SO4) and filter. Concentrate the filtrate and adsorb the crude product onto silica gel. Purify by silica gel chromatography eluting with ethyl acetate in dichloromethane (0-5 v/v %) to give 95.1 mg of the title compound (61%). LRMS (API ES+)=383.0 (M+H).

Workup

  1. temperatureCool
  2. customthe reaction to 0° C.
  3. customthe reaction
  4. customQuench
  5. customreaction with saturated aqueous sodium bicarbonate (5 mL)
  6. customseparate the layers
  7. washWash the organic layer with water (5 mL), brine (5 mL)
  8. dry with materialdry (Na2SO4)
  9. filtrationfilter
  10. concentrationConcentrate the filtrate
  11. customPurify by silica gel chromatography
  12. washeluting with ethyl acetate in dichloromethane (0-5 v/v %)

Sources & evidence

ORD record
ord-8d02089631dd460189f2b6f46e7bc3d4
Source dataset
uspto-grants-2011_04
Patent number
US07932284B2

Reaction notes

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