Sodium Carbonate → HCID 178517589, compound

HRID 595678Notes

Reaction equation

HRID 595678 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](I)[C:5]([OH:8])=[N:6][CH:7]=1.[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[CH:13]=[C:14](B(O)O)[NH:15]2.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[CH:3]=[C:4]([C:14]2[NH:15][C:16]3[C:12]([CH:13]=2)=[C:11]([F:10])[CH:19]=[CH:18][CH:17]=3)[C:5]([OH:8])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 90333436(4-fluoro-1H-indol-2-yl)boronic acidHCID 178517595HCID 178517595, compound

Product 1

HCID 178517589HCID 178517589, compoundYield 52.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-3-iodopyridin-2-ol (5 g, 16.7 mmol), (4-fluoro-1H-indol-2-yl)boronic acid (4.48 g, 25.0 mmol), sodium carbonate (3.53 g, 33.4 mmol) and Pd(dppf)Cl2 (200 mg) in 1,4-dioxane (50 mL) was stirred at 100° C. for 16 hours under nitrogen atmosphere. The mixture was filtered through celite and concentrated, and the residue was diluted with water and EA. After extracted with EA, the combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford crude 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-ol (3.5 g) through the column chromatography (DCM:EA=5:1). Finally the pure 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-ol (2.7 g, yield: 52%) was obtained by recrystallized from DCM:MeOH (10:1). 1H-NMR (DMSO-d6, 400 MHz) δ 12.36 (br s, 1H), 11.79 (s, 1H), 8.25 (s, 1H), 7.70 (s, 1H), 7.39 (s, 1H), 7.30 (d, J=8.00 Hz, 1H), 7.04˜7.07 (m, 1H), 6.74˜6.78 (m, 1H). MS (M+H)+: 307/309.

Workup

  1. filtrationThe mixture was filtered through celite and
  2. concentrationconcentrated
  3. additionthe residue was diluted with water and EA
  4. extractionAfter extracted with EA
  5. washthe combined organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto afford crude 5-bromo-3-(4-fluoro-1H-indol-2-yl)pyridin-2-ol (3.5 g) through the column chromatography (DCM:EA=5:1)

Sources & evidence

ORD record
ord-9acd07c3d9e14291b5730e48f324e012
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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