Potassium Phosphate, Tribasic → 2-(5-amino-pyridin-3-yl)-1-methyl-1H-indole

HRID 1661625Notes

Reaction equation

HRID 1661625 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](Br)[CH:7]=1.[CH3:9][N:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[C:11]1B(O)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>[NH2:1][C:2]1[CH:7]=[C:6]([C:11]2[N:10]([CH3:9])[C:18]3[C:13]([CH:12]=2)=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 8176813-Amino-5-bromopyridineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 22733820(1-Methyl-1H-indol-2-yl)boronic acid

Product 1

HCID 582155792-(5-amino-pyridin-3-yl)-1-methyl-1H-indole

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A flask is charged with 3-amino-5-bromopyridine (0.173 g, 0.950 mmol), N-methyl-indole boronic acid (0.262 g, 1.425 mmol), s-Phos (0.030 g, 0.071 mmol), finely crushed potassium phosphate (0.407 g, 1.900 mmol) and toluene (4 mL). After degassing for 30 min, Pd2dba3 (0.018 g, 0.019 mmol) is added, the flask is flushed with nitrogen and the mixture is heated to 85° C. After 3 h, the mixture is allowed to cool to r.t., diluted with ethyl acetate and filtered through a plug of silica gel (elution with ethyl acetate). The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:7 to 0:1) to give 2-(5-amino-pyridin-3-yl)-1-methyl-1H-indole as an off-white powder. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.74 (s, 3H), 5.49 (s, 2H), 6.56 (s, 1H), 7.05-7.09 (m, 1H), 7.09-7.10 (m, 1H), 7.17-7.21 (m, 1H), 7.49 (d, J=7.6 Hz, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.94 (d, J=2.0 Hz, 1H), 7.99 (d, J=2.5 Hz, 1H). MS (ESI) m/z 224 (M+H)+.

Workup

  1. customAfter degassing for 30 min
  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 (elution with ethyl acetate)
  6. customThe residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:7 to 0:1)

Sources & evidence

ORD record
ord-9de6eeb4514d4cd58548dbed6fd6464c
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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