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

HRID 1522639Notes

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

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), sodium carbonate (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 and filtered through a pad of Celite®, rinsed with dioxane (3×50 mL) and the filtrate was concentrated directly onto silica gel and then purified by column chromatography on NH silica eluted with 0-100% ethyl acetate/hexanes 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

temperatureThe reaction was cooled
filtrationfiltered through a pad of Celite®
washrinsed with dioxane (3×50 mL)
concentrationthe filtrate was concentrated directly onto silica gel
custompurified by column chromatography on NH silica
washeluted with 0-100% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-411855efcb55429eab66713ff5d2a914
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073918B2

Reaction notes

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