Sodium Bicarbonate → 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol

HRID 595656Notes

Reaction equation

HRID 595656 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](I)[C:5]([OH:9])=[CH:4][CH:3]=1.C(OC([N:17]1[C:25]2[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=2)[CH:19]=[C:18]1B(O)O)=O)(C)(C)C.C([O-])(O)=O.[Na+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:18]2[NH:17][C:25]3[C:20]([CH:19]=2)=[CH:21][C:22]([F:26])=[CH:23][CH:24]=3)[C:5]([OH:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27632925-Fluoro-1H-indole-2-boronic acid, N-BOC protectedHCID 234331586-Chloro-2-iodo-3-hydroxypyridine

Product 1

HCID 903334926-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-olYield 58.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 6-chloro-2-iodopyridin-3-ol (1.0 g, 3.91 mmol) and (1-(tert-butoxycarbonyl)-5-fluoro-1H-indol-2-yl)boronic acid (prepared using the method described in Example 1, 1.3 g, 4.66 mmol) in 1,4-dioxane-H2O (20 mL, 10:1), Pd(PPh3)2Cl2 (120 mg) and NaHCO3 (1.0 g, 11.90 mmol) were added under N2. The mixture was heated to 100° C. overnight. The reaction mixture was cooled to room temperature, filtered and washed with EtOAc. The filtrate was washed with H2O, brine, dried over Na2SO4. After concentrated, the residue was purified by column chromatography (PE:EA 5:1) to give the product of 6-chloro-2-(5-fluoro-1H-indol-2-yl)pyridin-3-ol (600 mg, yield: 58.2%). 1H-NMR (DMSO-d6, 400 MHz) δ 11.37 (br s, 1H), 11.03 (s, 1H), 7.51 (dd, J=8.8, 4.8 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.34 (dd, J=10.0, 2.4 Hz, 1H), 7.30 (d, J=1.2 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 6.94˜6.99 (m, 1H). MS (M+H)+: 263/265.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washwashed with EtOAc
  4. washThe filtrate was washed with H2O, brine
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentrated
  7. customthe residue was purified by column chromatography (PE:EA 5:1)

Sources & evidence

ORD record
ord-d73cc226d6fc4924a63b21438d1c78c8
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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