6-Chloro-2-iodo-3-hydroxypyridine → HCID 86728233, compound

HRID 1776818Notes

Reaction equation

HRID 1776818 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](I)[C:5]([OH:9])=[CH:4][CH:3]=1.[CH3:10][Si:11]([CH3:29])([CH3:28])[CH2:12][CH2:13][O:14][CH2:15][N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH:18]=[C:17]1B(O)O>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]>[Cl:1][C:2]1[N:7]=[C:6]([C:17]2[N:16]([CH2:15][O:14][CH2:13][CH2:12][Si:11]([CH3:29])([CH3:28])[CH3:10])[C:20]3=[N:21][CH:22]=[CH:23][CH:24]=[C:19]3[CH:18]=2)[C:5]([OH:9])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 234331586-Chloro-2-iodo-3-hydroxypyridineHCID 68111616(1-{[2-(Trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acid

Product 1

HCID 86728233HCID 86728233, compoundYield 29.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a mixture of 6-chloro-2-iodopyridin-3-ol (8.39 g, 32.85 mmol), (1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)boronic acid (8.00 g, 27.38 mmol) and K3PO4.3H2O (22 mg, 82.13 mmol) in 1,4-dioxane (120 mL), Pd(dppf)Cl2 (50 mg) was added under N2 protection. After stirred overnight at 80° C., the reaction mixture was concentrated in vacuo, suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (petroleum ether:EtOAc=5:1) to provide the product of 6-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)pyridin-3-ol (3.01 g, yield: 29%). 1H-NMR (CDCl3, 400 MHz) δ 8.40 (dd, J=4.8 Hz, 1.6 Hz, 1H), 7.96 (dd, J=8.0 Hz, 1.6 Hz, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.17 (dd, J=8.0 Hz, 4.8 Hz, 1H), 6.82 (s, 1H), 5.85 (s, 2H), 3.65 (t, J=8.4 Hz, 2H), 0.89 (t, J=8.4 Hz, 2H), −0.08 (s, 9H). MS (M+H)+: 376/378.

Workup

  1. additionwas added under N2 protection
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-30114c47b6cf4b0594e8cb58097c5e4f
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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