Potassium Carbonate → 7-bromo-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-3,4-dihydro-1,6-naphthyridin-2(1H)-one

HRID 394179Notes

Reaction equation

HRID 394179 reaction equation
Br[C:2]1[CH:7]=[C:6]([Br:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[Cl:16])[C:3]=1[CH2:17][CH2:18][C:19]([NH:21][C:22]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=1[Cl:29])=[O:20].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[Cu]I>[Br:8][C:6]1[CH:7]=[C:2]2[C:3]([CH2:17][CH2:18][C:19](=[O:20])[N:21]2[C:22]2[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:29])=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[Cl:16])[N:5]=1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 226479113-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]-N-(2,6-dichlorophenyl)propanamide

Product 1

HCID 226480887-bromo-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-3,4-dihydro-1,6-naphthyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
155 °C

Procedure

To 3-[4,6-dibromo-2-(2-chloro-4-fluorophenyl)pyridin-3-yl]-N-(2,6-dichlorophenyl)propanamide (3.14 g, 5.40 mmol) in DMF (50 mL) was added K2CO3 (1.49 g, 10.8 mmol) and CuI (1.54 g, 10.8 mmol). The resulting reaction mixture was evacuated and purged with argon 3 times, and then heated at 155° C. (oil bath) for 35 min. The reaction mixture was cooled to rt and diluted with 240 mL of half-saturated aqueous NaHCO3 and 120 mL of ethyl acetate. The layers were separated and the aqueous layer was extracted with 2×180 mL of ethyl acetate. The combined organic layers were washed with 120 mL of brine, dried over Na2SO4, and concentrated under reduced pressure. The product was purified by flash chromatography on 2 Biotage 40M columns, eluting with 50:50 hexanes-CH2Cl2 to yield 7-bromo-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-3,4-dihydro-1,6-naphthyridin-2(1H)-one. Mass spectrum (ESI) 499.2 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. customwas evacuated
  3. custompurged with argon 3 times
  4. temperatureThe reaction mixture was cooled to rt
  5. additiondiluted with 240 mL of half-saturated aqueous NaHCO3 and 120 mL of ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with 2×180 mL of ethyl acetate
  8. washThe combined organic layers were washed with 120 mL of brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe product was purified by flash chromatography on 2 Biotage 40M columns
  12. washeluting with 50:50 hexanes-CH2Cl2

Sources & evidence

ORD record
ord-d8e60045b6bb4edcb5b2d4587095ea74
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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