Potassium Carbonate → 4-Fluoro-N-(2-{4-[2-(1H-indol-4-yl)-pyridin-3-yl]-piperazin-1-yl}-ethyl)-N-methyl-benzenesulfonamide hydrochloride

HRID 553516Notes

Reaction equation

HRID 553516 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:27])[S:17]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:28]1[C:36]2[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[C:31]=2[CH:30]=[CH:29]1.C(=O)([O-])[O-].[K+].[K+].B(O)O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[F:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([N:16]([CH2:15][CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:7]3[C:2]([C:32]4[CH:33]=[CH:34][CH:35]=[C:36]5[C:31]=4[CH:30]=[CH:29][NH:28]5)=[N:3][CH:4]=[CH:5][CH:6]=3)[CH2:9][CH2:10]2)[CH3:27])(=[O:19])=[O:18])=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 27631731H-Indole-4-boronic acidHCID 86640209N-{2-[4-(2-Chloro-pyridin-3-yl)-piperazin-1-yl]-ethyl}-4-fluoro-N-methyl-benzenesulfonamide

Product 1

HCID 673670934-Fluoro-N-(2-{4-[2-(1H-indol-4-yl)-pyridin-3-yl]-piperazin-1-yl}-ethyl)-N-methyl-benzenesulfonamide hydrochlorideYield 15.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Dissolve N-{2-[4-(2-chloro-pyridin-3-yl)-piperazin-1-yl]-ethyl}-4-fluoro-N-methyl-benzenesulfonamide (0.160 g, 0.387 mmol) in DME (5 mL, previously degassed with nitrogen). Add 4-indole boronic acid (0.094 g, 0.581 mmol), 2N aqueous potassium carbonate (0.464 mL, 0.129 g, 0.930 mmol), and tetrakis(triphenylphosphine)palladium (0.022 g, 0.022 mmol). Stir the reaction mixture at 80° C. for 18 hr. Add fresh catalyst (0.015 g) and boronic acid (0.050 g). Stir an additional 8 hr. at 95° C. Cool to room temperature and concentrate to remove DME. Dilute with ethyl acetate and brine. Extract the aqueous layer with ethyl acetate. Combine the organic layers, dry over sodium sulfate, filter, and concentrate. Purify the resulting material by silica gel chromatography eluting with dichloromethane:methanol 94:6 to 90:10 to afford the title compound (0.031 g).

Workup

  1. custompreviously degassed with nitrogen)
  2. stirringStir an additional 8 hr
  3. customat 95° C
  4. temperatureCool to room temperature
  5. concentrationconcentrate
  6. customto remove DME
  7. additionDilute with ethyl acetate and brine
  8. extractionExtract the aqueous layer with ethyl acetate
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the resulting material by silica gel chromatography
  13. washeluting with dichloromethane:methanol 94:6 to 90:10

Sources & evidence

ORD record
ord-4bdadbb919334267b45f5d2714c15373
Source dataset
uspto-grants-2011_11
Patent number
US08048884B2

Reaction notes

Loading…