Sodium Carbonate → 2-(2,5-Difluorophenyl)-5-methylpyridin-4-amine

HRID 1522636Notes

Reaction equation

HRID 1522636 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([CH3:9])=[CH:4][N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1B(O)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>[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([CH3:9])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 126437092-Bromo-5-methylpyridin-4-amine

Product 1

HCID 674696792-(2,5-Difluorophenyl)-5-methylpyridin-4-amine

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

Bis(triphenylphosphine)palladium chloride (0.927 g, 1.321 mmol), 2-bromo-5-methylpyridin-4-amine (2.47 g, 13.21 mmol), Na2CO3 (6.60 mL, 13.21 mmol) and 2,5-difluorophenylboronic acid (2.71 g, 17.17 mmol) were combined and heated at 95° C. overnight. The reaction was cooled, filtered through a pad of Celite®, and concentrated directly onto silica gel and then purified by column chromatography (NH, silica) eluted with EtOAc/hexanes (0-100%) to give 2-(2,5-difluorophenyl)-5-methylpyridin-4-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.05 (3H, s) 5.96 (2H, s) 7.04 (1H, d, J=2.02 Hz) 7.20-7.29 (1H, m) 7.29-7.38 (1H, m) 7.68 (1H, ddd, J=9.73, 6.19, 3.28 Hz) 8.02 (1H, s). MS [M+H] found 221.2.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of Celite®
  3. concentrationconcentrated directly onto silica gel
  4. custompurified by column chromatography (NH, silica)
  5. washeluted with EtOAc/hexanes (0-100%)

Sources & evidence

ORD record
ord-32d7d429f6d24611a2d2b4ec6c5b8693
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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