2-Aminopyridine → (3-Fluoro-2-methyl-6-nitro-phenyl)-pyridin-2-ylamine

HRID 243059Notes

Reaction equation

CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17](F)[C:16]=1[CH3:25]>C1COCC1.O>[F:14][C:15]1[C:16]([CH3:25])=[C:17]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Potassium tert-butoxide (2.59 g, 23.1 mmol) was added to a solution of 2-aminopyridine (1.14 g, 12.1 mmol) in THF (30 mL) at 0° C. and the reaction mixture stirred at 0° C. for 20 min. 1,3-Difluoro-2-methyl-4-nitrobenzene (2 g, 11.6 mmol) was added as a solution in THF (10 mL) and the reaction mixture stirred at 0° C. for 30 min. 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 g, 70%). 1H NMR 400 MHz δ (CDCl3): 8.53 (1H, br s), 8.19 (1H, ddd, J=5.1, 1.9, 0.8 Hz), 8.02 (1H, dd, J=9.2, 5.7 Hz), 7.57 (1H, ddd, J=8.2, 7.3, 1.9 Hz), 6.94 (1H, dd, J=9.1, 8.2 Hz), 6.86 (1H, ddd, J=7.3, 5.1, 1.0 Hz), 6.69 (1H, dt, J=8.3, 0.9 Hz), 2.06 (3H, d, J=2.8 Hz).

Workup

stirringthe reaction mixture stirred at 0° C. for 30 min
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-b1cb19b6362b4091a95d39ae07192a08
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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