1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 6-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one

HRID 449684노트

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HRID 449684 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]2[N:8]=[C:9]([NH2:11])[CH:10]=[C:4]2[CH2:3]1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=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>O1CCOCC1.ClCCl.O.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:19][C:17]1[CH:18]=[C:13]([NH:11][C:9]2[CH:10]=[C:4]3[CH2:3][N:2]([CH3:1])[CH2:7][CH2:6][N:5]3[N:8]=2)[C:14](=[O:21])[N:15]([CH3:20])[N:16]=1

참가 물질

8

반응물 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 580439335-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

생성물 1

HCID 666346996-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one수율 57%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

A solution of 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine (55.7 mg, 0.37 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (81.8 mg, 0.37 mmol) cesium carbonate (417 mg, 1.28 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (31.8 mg, 0.05 mmol) in dioxane (6 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (25.1 mg, 0.03 mmol) was added and the resulting solution was heated at 90° C. for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane (50 mL) and water. The layers were separated and the aqueous layer was extracted with dichloromethane (2×25 mL). The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 24 g, 2% to 7% methanol in dichloromethane) to give 6-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one (61 mg, 57%) as a light yellow solid.

후처리

  1. additionwas added
  2. temperatureThe mixture was cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (2×25 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe resulting mixture was filtered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 24 g, 2% to 7% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-0468973b5e654861818b9ad94f320749
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481540B2

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