Cesium carbonate → Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

HRID 449619노트

반응식

HRID 449619 반응식
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=1.[NH2:11][C:12]1[N:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:14][CH:13]=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:8][C:6]1[CH:7]=[C:2]([NH:11][C:12]2[N:17]=[CH:16][C:15]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[C:3](=[O:10])[N:4]([CH3:9])[N:5]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 49839963tert-Butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylateHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

생성물 1

HCID 66742247Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate수율 82%

시약·촉매·용매 2

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

반응 조건

온도
90 °C

실험 절차

4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one (509 mg, 2.28 mmol, Eq: 1.00), tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate (632 mg, 2.28 mmol, Eq: 1.00), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (198 mg, 342 μmol, Eq: 0.15) and cesium carbonate (2.6 g, 7.98 mmol, Eq: 3.5) were suspended in dioxane (20 ml) under argon. Finally tris(dibenzylideneacetone)dipalladium(0) (156 mg, 171 μmol, Eq: 0.075) was added. The reaction mixture was heated to 90° C. for 18 h. The reaction mixture was filtered over celite; washed with dioxane, and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 20% to 50% EtOAc/Hex gradient) to give tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (782 mg, 82%). LC/MS-ESI observed [M+H]+ 420.

후처리

  1. filtrationThe reaction mixture was filtered over celite
  2. washwashed with dioxane
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 24 g, 20% to 50% EtOAc/Hex gradient)

출처 및 근거

ORD 기록
ord-72d246af21ea4e15835e5727dbbed3b3
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481540B2

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