Potassium Phosphate, Tribasic → HCID 58215691, compound

HRID 1661626Notes

Reaction equation

HRID 1661626 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:8]=[O:9])[CH:7]=1.C([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]1B(O)O)(OC(C)(C)C)=O.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].C1(C)C=CC=CC=1>[NH:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]1[C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)HCID 27847345-Bromo-3-pyridinecarboxaldehydeHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 58215691HCID 58215691, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A flask is charged with 3-bromopyridine-5-carboxaldehyde (4.12 g, 21.48 mmol), N-Boc-indoleboronic acid (8.59 g, 32.23 mmol), s-Phos (0.68 g, 1.61 mmol), finely crushed potassium phosphate (9.21 g, 42.97 mmol) and toluene (70 mL). After degassing for 1 h, Pd2dba3 (0.40 g, 0.43 mmol) is added, the flask is flushed with nitrogen and the mixture is heated to 85° C. After 30 min, the mixture is allowed to cool to r.t., diluted with ethyl acetate and filtered through a plug of silica gel. Silica gel (50 g) is added to the filtrate and the mixture is concentrated in vacuo. The residue is heated to 60° C. with gentle stirring under oil pump vacuum overnight. The mixture is then loaded on a silica gel flash chromatography column and eluted (heptane-ethyl acetate, 4:1 to 2:3) to give 5-(1H-indol-2-yl)-pyridine-3-carbaldehyde. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.02-7.08 (m, 1H), 7.14-7.19 (m, 1H), 7.20 (d, J=1.5 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.59 (d, J=8.1 Hz, 1H), 8.66 (t, J=2.1 Hz, 1H), 9.00 (d, J=1.8 Hz, 1H), 9.39 (d, J=2.3 Hz, 1H), 10.18 (s, 1H), 11.86 (br. s., 1H). MS (ESI) m/z 223.02 (M+H)+.

Workup

  1. customAfter degassing for 1 h
  2. customthe flask is flushed with nitrogen
  3. temperatureto cool to r.t.
  4. additiondiluted with ethyl acetate
  5. filtrationfiltered through a plug of silica gel
  6. additionSilica gel (50 g) is added to the filtrate
  7. concentrationthe mixture is concentrated in vacuo
  8. temperatureThe residue is heated to 60° C.
  9. washeluted (heptane-ethyl acetate, 4:1 to 2:3)

Sources & evidence

ORD record
ord-2e4c5a5cc73b490aaffbbdac9fcad0b5
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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