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

HRID 242913Notes

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].[NH4+].[Cl-]>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, 12.6 mL, 12.6 mmol) was added dropwise to a stirred solution of pyridin-3-ylamine (621 mg, 6.60 mmol) in anhydrous THF (10 mL) under a nitrogen atmosphere at −78° C. After 45 min stirring at −78° C., a solution of 2,4-difluoro-1-nitrobenzene (690 μL, 6.29 mmol) in THF (10 mL) was added and stirring continued for 1 h. The solution was poured into an aqueous solution of NH4Cl (100 mL) and extracted with EtOAc (×3). The combined organic fractions were washed with water, followed by brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was triturated with EtOAc to afford the title compound as a dark orange solid (638 mg). The mother liquours were concentrated under reduced pressure to afford the title compound as a dark orange solid (648 mg, 87% for the combined batches). 1H NMR (CDCl3, 400 MHz): δ 9.60 (1H, br s), 8.63 (1H, s), 8.56 (1H, d, J=4.76 Hz), 8.35-8.27 (1H, m), 7.65 (1H, d, J=8.20 Hz), 7.45-7.38 (1H, m), 6.75 (1H, d, J=11.14 Hz), 6.57 (1H, t, J=8.24 Hz)

Workup

stirringstirring
waitcontinued for 1 h
extractionextracted with EtOAc (×3)
washThe combined organic fractions were washed with water
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe resulting residue was triturated with EtOAc

Sources & evidence

ORD record: ord-97904e6db19f4368a522f183a303aa1a
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

Loading…