Cesium carbonate → 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one

HRID 449626

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HRID 449626 반응식
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH2:8])=[N:3]1.Br[C:10]1[C:11](=[O:18])[N:12]([CH3:17])[N:13]=[C:14]([Cl:16])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[Cl:16][C:14]1[CH:15]=[C:10]([NH:8][C:4]2[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[N:3]=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 70177471,5-dimethyl-1H-pyrazol-3-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

생성물 1

HCID 585400026-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one수율 45%

시약·촉매·용매 2

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

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온도
100 °C

실험 절차

1,5-Dimethyl-1H-pyrazol-3-amine (400 mg, 3.6 mmol, Eq: 1.00) and 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (965 mg, 4.32 mmol, Eq: 1.20) were combined with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (312 mg, 540 μmol, Eq: 0.15), cesium carbonate (3.52 g, 10.8 mmol, Eq: 3) and tris(dibenzylideneacetone)dipalladium(0) (165 mg, 180 μmol, Eq: 0.05) in dioxane (10.0 ml). The solution was degassed with Ar. The reaction mixture heated at 100° C. for 18 h. The mixture was cooled to room temperature. The solution was diluted with 100 ml DCM. The organic layer was washed with water. The organic layer was dried over MgSO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 10% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one (408 mg, 45%). LC/MS-ESI observed [M+H]+ 235.

후처리

  1. customThe solution was degassed with Ar
  2. temperatureThe mixture was cooled to room temperature
  3. additionThe solution was diluted with 100 ml DCM
  4. washThe organic layer was washed with water
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 40 g, 10% to 50% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

출처 및 근거

ORD 기록
ord-f11b21d7a2524c56a7cec9bb7997d557
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481540B2

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