2-Aminopyridine → (2-Bromo-3-fluoro-6-nitro-phenyl)-pyridin-2-yl-amine

HRID 243054Notes

Reaction equation

CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1.[Br:14][C:15]1[C:20](F)=[C:19]([N+:22]([O-:24])=[O:23])[CH:18]=[CH:17][C:16]=1[F:25]>C1COCC1.O>[Br:14][C:15]1[C:16]([F:25])=[CH:17][CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[C:20]=1[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Potassium tert-butoxide (2.82 g, 25.2 mmol) was added to a solution of 2-aminopyridine (1.25 g, 13.2 mmol) in THF (40 mL) at 0° C. and the reaction mixture stirred at 0° C. for 30 min. 2-Bromo-1,3-difluoro-4-nitrobenzene (3 g, 12.6 mmol) was added as a solution in THF (10 mL) and the reaction mixture stirred at 0° C. for 2 h. The reaction mixture was diluted with water and the product extracted with EtOAc (3×40 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) to yield the title compound as a yellow solid (2.38 g, 60%). 1H NMR 400 MHz δ (CDCl3): 8.16 (1H, ddd, J=5.1, 2.0, 1.0 Hz), 8.08 (1H, dd, J=9.3, 5.6 Hz), 7.82 (1H, br s), 7.62 (1H, ddd, J=8.1, 7.3, 1.8 Hz), 6.99 (1H, dd, J=9.2, 7.1 Hz), 6.91 (1H, ddd, J=7.3, 5.0, 1 Hz), 6.82 (1H, dt, J=8.3, 1.0 Hz).

Workup

stirringthe reaction mixture stirred at 0° C. for 2 h
extractionthe product extracted with EtOAc (3×40 mL)
washThe combined organic extracts were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-e6be7a2d098f48ef9acad40b4013857c
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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