Potassium Phosphate, Tribasic → 5-(6-chloro-1H-indol-2-yl)-pyridine-3-carbaldehyde

HRID 593582Notes

Reaction equation

HRID 593582 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)[CH:10]=[C:9]1B(O)O)=O)(C)(C)C.Br[C:22]1[CH:23]=[N:24][CH:25]=[C:26]([CH:29]=1)[CH:27]=[O:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:17][C:14]1[CH:15]=[C:16]2[C:11]([CH:10]=[C:9]([C:22]3[CH:29]=[C:26]([CH:27]=[O:28])[CH:25]=[N:24][CH:23]=3)[NH:8]2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27847345-Bromo-3-pyridinecarboxaldehydeHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 441191511-Boc-6-chloroindole-2-boronic acid

Product 1

HCID 582157125-(6-chloro-1H-indol-2-yl)-pyridine-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
85 °C

Procedure

A flask is charged with N-(tert-butoxycarbonyl)-6-chloro-1H-indol-2-ylboronic acid (8.3 g, 28.1 mmol), 5-bromonicotinaldehyde (4.35 g, 23.4 mmol), K3PO4 (9.94 g, 46.8 mmol), s-Phos (0.480 g, 1.170 mmol) and Pd2(dba)3 (0.429 g, 0.468 mmol), and the flask is flushed with N2. Toluene (250 mL) is added, and the mixture is heated to 85° C. for 1.5 h. The mixture is cooled to room temperature. Ethyl acetate (250 mL) is added and the mixture is filtered through a pad of silica gel, which is washed with EtOAc. Silica gel is added to the combined filtrate, which is concentrated in vacuo. The residue is placed under high vacuum at 63° C. overnight, and after elution with ethyl acetate, 5-(6-chloro-1H-indol-2-yl)-pyridine-3-carbaldehyde is obtained. MS (ESI) m/z 257.0 and 258.9 (M+H)+.

Workup

  1. customthe flask is flushed with N2
  2. additionToluene (250 mL) is added
  3. temperatureThe mixture is cooled to room temperature
  4. additionEthyl acetate (250 mL) is added
  5. filtrationthe mixture is filtered through a pad of silica gel, which
  6. washis washed with EtOAc
  7. additionSilica gel is added to the combined filtrate, which
  8. concentrationis concentrated in vacuo
  9. washafter elution with ethyl acetate

Sources & evidence

ORD record
ord-8f21af8a22834822af67bae66315afd0
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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