Tetrahydrofuran → 5-(4-Fluorophenyl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-Indole

HRID 278003Notes

Reaction equation

HRID 278003 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.[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+].O1CCCC1>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.C(Cl)(Cl)Cl>[F:25][C:26]1[CH:31]=[CH:30][C:29]([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[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 120418125-Trifluoromethanesulfonyloxy-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine

Product 1

HCID 98614675-(4-Fluorophenyl)-3-(1-Methylpiperidin-4-yl)-4-Aza-1H-IndoleYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
75 °C

Procedure

O-Trifluoromethanesulfonyl-3-(1-methylpiperidin-4-yl)-5-hydroxy-4-aza-1H-indole (150 mg, 0.412 mmol), 4-fluorophenylboronic acid (87 mg, 0.619 mmol), tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.041 mmol), 4 mL of 2M aqueous sodium bicarbonate, and 30 mL of tetrahydrofuran were placed in a round bottom flask. The mixture was heated to reflux (about 75° C.) and allowed to stir for about 18 hours. The reaction was poured into 3:1 chloroform:isopropyl alcohol, extracted three times each with 1N aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed (silica gel, 0-10% methanol/dichloromethane) to give 87.9 mg of the title compound. (79%). MS(FD) m/e 309.6 (M+). EA calculated for C19H20FN3: C, 73.79; H, 6.47; N, 13.59. Found: C, 73.69; H, 6.73; N, 13.40.

Workup

  1. temperatureThe mixture was heated
  2. extractionisopropyl alcohol, extracted three times each with 1N aqueous sodium hydroxide and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed (silica gel, 0-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-14d97597f0f54c4e825e32ddaec5e856
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Reaction notes

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