Chlorosuccinimide → 3-chloro-4-[(2,4-difluorobenzyl)amino]-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one

HRID 1832062Notes

Reaction equation

HRID 1832062 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]([CH3:15])=[CH:13][C:12](O)=[CH:11][C:10]1=[O:17].[F:18][C:19]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:20]=1[CH2:21][NH2:22].[Cl:28]N1C(=O)CCC1=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:28][C:11]1[C:10](=[O:17])[N:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])[C:14]([CH3:15])=[CH:13][C:12]=1[NH:22][CH2:21][C:20]1[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:19]=1[F:18]

Participants

6

Reactant 4

HCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 27332442,4-DifluorobenzylamineHCID 54724198HCID 54724198, compound

Product 1

HCID 220499093-chloro-4-[(2,4-difluorobenzyl)amino]-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-oneYield 6.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one (0.3 g, 1.26 mmol) and 2,4-difluoro benzylamine (1 mL, 84 mmol) were combined in an nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h. The excess amine was distilled in vacuo and the residue was used without further purification. N-Chloro succinimide (168 mg, 1.26 mmol) was added to a solution of the residue in methylene chloride (10 mL). After stirring at 25 C for 1 h, the reaction mixture was poured into saturated aqueous NaHCO3. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na2SO4, and concentrated in vacuo. The residue was chromatographed on silica (25:75 hexanes: ethyl acetate) to give the title compound (32 mg, 6%). 1H NMR (400 MHz, CD3OD) δ 7.55 (m, 1H), 7.36 (q, J=9.2 and 15.2 Hz, 1H), 7.18 (t, J=7.6 Hz, 2H), 6.98 (m, 2H), 6.15 (s, 1H), 4.62 (s, 2H), 1.96 (s, 3H) ppm. 19 F NMR (400 MHz, CD3OD) δ−113.78 (1 F), −116.72 (1 F), −121.57 (1 F) ppm. ES-HRMS m/z 397.0752 (M+H calcd for C19H14ClF4N2O requires 397.0725).

Workup

  1. customThe tube was capped
  2. temperatureheated at 180 C for 24 h
  3. distillationThe excess amine was distilled in vacuo
  4. customthe residue was used without further purification
  5. extractionThe aqueous mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried with anhydrous Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was chromatographed on silica (25:75 hexanes: ethyl acetate)

Sources & evidence

ORD record
ord-426ccc55716d4936b231ea7956c72ea2
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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