Sodium Methoxide → 2-Chloro-N-(2,4-difluorophenyl)-4-methoxynicotinamide

HRID 1986089Notes

Reaction equation

[CH3:1][O-:2].[Na+].[Cl:4][C:5]1[N:21]=[CH:20][CH:19]=[C:18](I)[C:6]=1[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])=[O:8]>CO>[Cl:4][C:5]1[N:21]=[CH:20][CH:19]=[C:18]([O:2][CH3:1])[C:6]=1[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])=[O:8]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of sodium methoxide (0.023 g, 0.43 mmol) in anhydrous methanol (3 mL) was added 2-chloro-N-(2,4-difluorophenyl)-4-iodonicotinamide (0.17 g, 0.43 mmol). The mixture was heated at 60° C. for 12 hours then allowed to cool to ambient temperature. Concentration of the reaction mixture resulted in a residue that was triturated with methanol and water. Isolation by vacuum filtration afforded the desired compound (0.035 g) as an off-white solid. The filtrate was concentrated in vacuo to a residue that was purified by flash column chromatography (SiO2, eluting with 25-100% EtOAc in hexane) to afford an additional amount desired compound (0.049 g, overall yield 65%) that was spectroscopically consistant with the initially isolated material. 1H NMR (DMSO-d6) δ 10.48 (s, 1H), 8.38 (d, 1H, J=5.8 Hz), 7.85-7.96 (m, 1H), 7.33-7.40 (m, 1H), 7.27 (d, 1H, J=5.8 Hz), 7.05-7.20 (m, 1H), 3.92 (s, 3H); MS(ESI+) m/z 299 (M+H)+.

Workup

temperatureto cool to ambient temperature
customConcentration of the reaction mixture resulted in a residue that
customwas triturated with methanol and water
filtrationIsolation by vacuum filtration

Sources & evidence

ORD record: ord-e4cbb7e5a3054ae58423014d8905a78d
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07547782B2

Reaction notes

Loading…