4-Chloroquinoline → 5-(Quinolin-4-yl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-Indole

HRID 278008

Reaction equation

HRID 278008 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+].Cl[C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]=[CH:30][CH:29]=1.C[Sn](C)C.C[Sn](C)C.[F-].[K+]>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.O1CCOCC1>[N:31]1[C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:28]([C:7]2[N:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][CH:11]=[C:10]3[CH:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[CH:29][CH:30]=1

Participants

8

Reactant 5

HCID 691404-ChloroquinolineHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 6327618HexamethylditinHCID 120418125-Trifluoromethanesulfonyloxy-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine

Product 1

HCID 98628845-(Quinolin-4-yl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-IndoleYield 45.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

O-Trifluoromethanesulfonyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-4-aza-1H-indole (239 mg, 0.658 mmol), tetrakis(triphenylphosphine)palladium(0) (76 mg, 0.065 mmol), dried lithium chloride (167 mg, 3.95 mmol), 4-chloroquinoline (108 mg, 0.658 mmol), hexamethylditin (215 mg, 0.658 mmol), and 15 mL of 1,4-dioxane were placed in a flask and heated to reflux (about 105° C.). The reaction was stirred for about 18 hours before 50 mL of 8M aqueous potassium fluoride solution was added. The solution was extracted with 3:1 chloroform:isopropanol and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (0-10% methanol:dichloromethane) to give 103 mg of the title compound. (46%). MS(FD) m/e 343.2 (M+H). EA calculated for C22H22N4: C, 77.16; H, 6.48; N, 16.36. Found: C, 76.98; H, 6.55; N, 16.29.

Workup

  1. temperatureheated
  2. additionwas added
  3. extractionThe solution was extracted with 3:1 chloroform
  4. dry with materialisopropanol and brine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel flash chromatography (0-10% methanol:dichloromethane)

Sources & evidence

ORD record
ord-c4f877cb1325475cab04bd5e252084bb
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Linked notes

Loading…