Lithium Chloride → 5-(Pyrid-2-yl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-Indole

HRID 278010Notes

Reaction equation

HRID 278010 reaction equation
FC(F)(F)S(O[C:7]1[N:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)(=O)=O.[Cl-].[Li+].C([Sn](CCCC)(CCCC)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1)CCC.[F-].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[N:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[C:7]1[N:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1

Participants

8

Reactant 4

HCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 6077842-(Tributylstannyl)pyridineHCID 120418125-Trifluoromethanesulfonyloxy-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine

Product 1

HCID 99480135-(Pyrid-2-yl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-IndoleYield 25.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

O-Trifluoromethanesulfonyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-4-aza-1H-indole (150 mg, 0.413 mmol), palladium(II)acetate (9.2 mg, 0.041 mmol), 1,1′-bis(diphenylphosphino)ferrocene (45 mg, 0.083), lithium chloride (105 mg, 2.48 mmol), and 15 mL of 1,4-dioxane were combined and stirred for 5 minutes. 2-Tributylstannylpyridine (197 μL, 0.537 mmol) was added and the mixture was heated to reflux (about 105° C.) and stirred for about 18 hours. 50 mL of 8M aqueous potassium fluoride solution was added and the solution was extracted with 3:1 chloroform:isopropanol and brine and concentrated in vacuo. The residue was purified by silica gel flash chromatography (0-20% methanol:dichloromethane) to give 31.1 mg of the title compound. (26%). MS(FD) m/e 293.1 (M+).

Workup

  1. temperaturethe mixture was heated
  2. stirringstirred for about 18 hours
  3. extractionthe solution was extracted with 3:1 chloroform
  4. concentrationisopropanol and brine and concentrated in vacuo
  5. customThe residue was purified by silica gel flash chromatography (0-20% methanol:dichloromethane)

Sources & evidence

ORD record
ord-f9737f96e1ac4aff9f062dc6927c17c6
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Reaction notes

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