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

HRID 1804717노트

반응식

HRID 1804717 반응식
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

참가 물질

8

반응물 4

HCID 284Formic Acid2회HCID 1140TolueneHCID 81531Diisopropylethylamine2회HCID 447548682-Chloro-5-fluoropyridin-3-amine

생성물 1

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

시약·촉매·용매 3

HCID 27342152-(Di-tert-butylphosphino)biphenyl촉매HCID 962Water용매HCID 8846Butyl Acrylate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-be03696fb99240869efdb81354ce8fcd
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354426B2

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