Cesium carbonate → 6-Chloro-2-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one

HRID 407697

반응식

HRID 407697 반응식
[CH2:1]([C:3]1[NH:7][N:6]=[C:5]([NH2:8])[CH:4]=1)C.Br[C:10]1[C:11](=[O:18])[N:12]([CH3:17])[N:13]=[C:14]([Cl:16])[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:16][C:14]1[CH:15]=[C:10]([NH:8][C:5]2[CH:4]=[C:3]([CH3:1])[NH:7][N:6]=2)[C:11](=[O:18])[N:12]([CH3:17])[N:13]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 219910953-ethyl-1H-pyrazol-5-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

생성물 1

HCID 866839736-Chloro-2-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)pyridazin-3(2H)-one수율 75.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (20 mL), 5-ethyl-1H-pyrazol-3-amine (971 mg, 10.0 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.46 g, 11.0 mmol), and cesium carbonate (6.52 g, 20.0 mmol). After bubbling nitrogen through the suspension for 10 minutes, xantphos (1.74 g, 3.0 mmol) and tris(dibenzylideneacetone)dipalladium(0) (1.37 g, 1.5 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 2 h. It was then filtered immediately when the reaction mixture was still hot. The solid was washed with dioxane (3×30 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel chromatography eluting with 6:1 petroleum ether/ethyl acetate to afford 127a (1.8 g, 75%) as a yellow solid. MS-ESI: [M+H]+ 239.9

후처리

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 2 h
  6. filtrationIt was then filtered immediately when the reaction mixture
  7. washThe solid was washed with dioxane (3×30 mL)
  8. concentrationthe combined filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica-gel chromatography
  10. washeluting with 6:1 petroleum ether/ethyl acetate

출처 및 근거

ORD 기록
ord-e9d4b8e6fc6b4e9fbba73c34e2b16a66
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754077B2

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