Formic Acid → 7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one

HRID 1804717Notes

Reaction equation

HRID 1804717 reaction equation
Cl[C:2]1[C:7]([NH2:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.[CH:10](N(C(C)C)CC)([CH3:12])[CH3:11].C(O)=[O:20].C1(C)C=CC=CC=1>C(OCCCC)(=O)C=C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.O>[F:9][C:5]1[CH:6]=[C:7]2[C:2]([CH2:11][CH2:10][C:12](=[O:20])[NH:8]2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 284Formic Acid2×HCID 1140TolueneHCID 81531Diisopropylethylamine2×HCID 447548682-Chloro-5-fluoropyridin-3-amine

Product 1

HCID 595107397-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-oneYield 63.5%

Reagents, catalysts & solvents 3

HCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 962WaterSolventHCID 8846Butyl AcrylateSolvent

Procedure

To a suspension of 25.0 g of 2-chloro-5-fluoropyridin-3-amine, 3.8 g of bis(tricyclohexyl phosphine)palladium (II) chloride and 1.5 g of 2-(di-tert-butylphosphino)biphenyl in 75 mL of butyl acrylate, 44.1 g of diisopropylethylamine was added, 15.7 g of formic acid was added dropwise thereto at room temperature, and the mixture was refluxed for 3 hours. To the reaction mixture, 32.1 g of diisopropylethylamine and 11.5 g of formic acid were added at 100° C., and the mixture was refluxed for 5 hours. The reaction mixture was cooled to 80° C., 50 mL of toluene and 75 mL of water were added thereto and the resultant mixture was cooled to room temperature. The solid product was obtained by filtration, and washed using in the order of toluene and water to give 18.0 g of 7-fluoro-3,4-dihydro-1,5-naphthyridin-2(1H)-one as a white solid.

Workup

  1. additionwas added
  2. temperaturethe mixture was refluxed for 5 hours
  3. temperatureThe reaction mixture was cooled to 80° C.
  4. customThe solid product was obtained by filtration
  5. washwashed

Sources & evidence

ORD record
ord-be03696fb99240869efdb81354ce8fcd
Source dataset
uspto-grants-2013_01
Patent number
US08354426B2

Reaction notes

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