3-Aminopyridine → (5-Fluoro-2-nitrophenyl)pyridin-3-ylamine

HRID 242961Notes

Reaction equation

[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=1.F[C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]>C1COCC1>[F:25][C:23]1[CH:22]=[CH:21][C:20]([N+:26]([O-:28])=[O:27])=[C:19]([NH:17][C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=2)[CH:24]=1

Participants

Conditions

Temperature: -78 °C

Procedure

LiHMDS (1.0M in THF, 50 mL, 50 mmol) was added dropwise to a stirred solution of pyridin-3-ylamine (2.5 g, 26.4 mmol) in anhydrous THF (20 mL) under a nitrogen atmosphere at −70° C. After 10 min stirring at −78° C., a solution of 2,4-difluoro-1-nitrobenzene (4.0 g, 25.1 mmol) in THF (40 mL) was added dropwise at −78° C. The reaction mixture was slowly warmed to RT. After 4 h stirring at RT, the crude mixture was quenched by addition of an aqueous solution of NH4Cl and the aqueous fraction extracted with EtOAc. The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo to afford the title compound as a red solid (quantitative). 1H NMR (CDCl3, 300 MHz): δ 9.58 (1H, br s), 8.61 (1H, d, J=2.64 Hz), 8.55 (1H, d, J=4.76 Hz), 8.29 (1H, dd, J=9.47, 5.92 Hz), 7.66-7.61 (1H, m), 7.40 (1H, dd, J=8.19, 4.75 Hz), 6.74 (1H, dd, J=10.95, 2.62 Hz), 6.60-6.51 (1H, m).

Workup

temperatureThe reaction mixture was slowly warmed to RT
stirringAfter 4 h stirring at RT
customthe crude mixture was quenched by addition of an aqueous solution of NH4Cl
extractionthe aqueous fraction extracted with EtOAc
washThe combined organic fractions were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-faa4689ffbc6495892858858abdb42ab
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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