Sodium hydride → 4-bromo-N-((4-chlorophenylamino)(2,6-difluorophenyl)methyl)benzamide

HRID 1920085

Reaction equation

[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.[H-].[Na+].[Cl:31][C:32]1[CH:47]=[CH:46][C:35]([N:36]=[CH:37][C:38]2[C:43]([F:44])=[CH:42][CH:41]=[CH:40][C:39]=2[F:45])=[CH:34][CH:33]=1>CN(C=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:8][CH:37]([NH:36][C:35]2[CH:46]=[CH:47][C:32]([Cl:31])=[CH:33][CH:34]=2)[C:38]2[C:43]([F:44])=[CH:42][CH:41]=[CH:40][C:39]=2[F:45])=[O:7])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

4-Bromobenzamide 117 (0.94 g, 4.56 mmol) and 18-crown-6 (1.2 g, 4.54 mmol) in DMF (6 mL) was treated with sodium hydride (0.37 g, 9.25 mmol) for 5 minutes at room temperature. 4-Chloro-N-(2,6-difluorobenzylidene)aniline 116 (0.936 g, 3.72 mmol) in DMF (4 mL) was added and the mixture was heated to 50° C. for 5 minutes. The reaction mixture was quenched with crushed ice and the product was isolated by a typical aqueous workup and extraction with ethyl acetate. Chromatographic purification (9:1 hexanes:ethyl acetate) followed by trituration (ethanol) of the material gave 4-bromo-N-((4-chlorophenylamino)(2,6-difluorophenyl)methyl)benzamide (Compound-6) as a white solid (292 mg, 17%). 1H NMR (300 MHz, CDCl3): δ=7.62-7.52 (series m, 4H), 7.38-7.28 (m, 1H), 7.19-7.15 (m, 2H), 7.14-7.08 (m, 1H), 7.02-6.96 (m, 2H), 6.88-6.85 (m, 1H), 6.76-6.72 (m, 2H).

Workup

customThe reaction mixture was quenched with crushed ice
customthe product was isolated by a typical aqueous workup and extraction with ethyl acetate
customChromatographic purification (9:1 hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-475b8e8fc1b94fdfab8ff14b770ccd56
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168795B2

Linked notes

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