Acetic Acid → 6-(4-chloro-1H-imidazol-1-yl)-5-methoxypyridin-3-amine

HRID 1803162Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[C:12]([O:13][CH3:14])=[CH:11][C:10]([N+:15]([O-])=O)=[CH:9][N:8]=2)[CH:6]=1.C(O)C.C(O)(=O)C.[OH-].[Na+]>[Fe].O>[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:8]=[CH:9][C:10]([NH2:15])=[CH:11][C:12]=2[O:13][CH3:14])[CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Step O (2): Iron powder-325 mesh (2.19 g, 39.3 mmol) was added to a flask charged with a mixture of 2-(4-chloro-1H-imidazol-1-yl)-3-methoxy-5-nitropyridine (5.0 g, 19.64 mmol), absolute ethanol (50 mL), and glacial acetic acid (20 mL). A water-cooled reflux condenser was attached to the flask and the heterogeneous mixture was heated to 100° C. with vigorous stirring for 30 min. The reaction mixture was allowed to cool to rt and was neutralized upon addition to a chilled and vigorously stirred solution of 5 M NaOH. The resulting mixture was poured into a reparatory funnel and extracted with EtOAc. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford 6-(4-chloro-1H-imidazol-1-yl)-5-methoxypyridin-3-amine (3.12 g, 71% yield). LC-MS (M+H)+ 225.1. 1H NMR (500 MHz, chloroform-d) δ ppm 8.06 (d, J=1.83 Hz, 1 H) 7.53 (dd, J=13.28, 1.98 Hz, 2 H) 6.70 (d, J=2.44 Hz, 1 H) 3.90 (s, 3 H) 3.86 (br. s., 2 H).

Workup

temperaturereflux condenser
temperatureto cool to rt
additionwas neutralized upon addition to
temperaturea chilled
additionThe resulting mixture was poured into a reparatory funnel
extractionextracted with EtOAc
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1b5528055ca741568a2a5e81e62f3ea4
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349880B2

Reaction notes

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