Sodium Carbonate → 3-(pyridin-3-yl)-1H-indazole-6-carbaldehyde

HRID 1615303Notes

Reaction equation

HRID 1615303 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[NH:4][N:3]=1.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15](B(O)O)[CH:14]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.CCO.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>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:2]2[C:10]3[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=3)[NH:4][N:3]=2)[CH:14]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 178519327HCID 178519327, compound

Product 1

HCID 866519663-(pyridin-3-yl)-1H-indazole-6-carbaldehyde

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 3-iodo-1H-indazole-6-carbaldehyde (50 mg, 0.18 mmol), pyridin-3-ylboronic acid (27 mg, 0.22 mmol), PdCl2(PPh3)2 (13 mg, 0.018 mmol) and 2M Na2CO3 (0.10 mL, 0.18 mmol) in DME/H2O/EtOH (1.4 mL/0.4 mL/0.2 mL) was degassed by evacuation and refilling with Ar. The reaction mixture was sealed and heated with stirring under microwave irradiation at 125° C. for 60 min. The crude reaction mixture was concentrated under reduced pressure. Ethyl acetate (5 mL) was added and the solution was washed with brine (2×20 mL), dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel using MeOH (5%) in DCM as the eluent to provide the title compound a pale yellow solid (24 mg, 59%). 1H NMR (400 MHz, CDCl3) δ ppm 10.17 (s, 1H), 8.88 (d, J=2.3 Hz, 1H), 8.69 (d, J=4.8 Hz, 1H), 8.16 (d, J=8.5 Hz, 1H), 8.10 (s, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.82 (d, J=8.5 Hz, 1H), 7.45 (dd, J=8.0, 5.0 Hz, 1H); MS ESI 224.0 (100) [M+H]+, calcd for [C13H9N3O+H]+ 224.07.

Workup

  1. customwas degassed by evacuation and refilling with Ar
  2. customThe reaction mixture was sealed
  3. temperatureheated
  4. customThe crude reaction mixture
  5. concentrationwas concentrated under reduced pressure
  6. additionEthyl acetate (5 mL) was added
  7. washthe solution was washed with brine (2×20 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-893ba21f47eb436696c9c42710d522ea
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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