Water → 1-methyl-N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide

HRID 626506

반응식

HRID 626506 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:24][N:25]1[CH2:30][CH2:29][CH:28]([C:31]([NH2:33])=[O:32])[CH2:27][CH2:26]1.O>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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH3:24][N:25]1[CH2:30][CH2:29][CH:28]([C:31]([NH:33][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)=[O:32])[CH2:27][CH2:26]1

참가 물질

8

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 3390111-Methylpiperidine-4-carboxamideHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

생성물 1

HCID 904108531-methyl-N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide수율 56.3%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매2회HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

A mixture of Example A1 (0.25 g, 0.994 mmol), Cs2CO3 (0.486 g, 1.490 mmol), 1-methylpiperidine-4-carboxamide (0.155 g, 1.093 mmol), and X-phos (0.024 g, 0.050 mmol) in dioxane (5 mL) was sparged with Ar, treated with Pd2(dba)3 (0.045 g, 0.050 mmol) and heated at 90° C. overnight. Additional X-phos (17 mg) and Pd2(dba)3 (30 mg) were added and the mixture heated at 90° C. for 7 h. The mixture was cooled to RT, treated with water and extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 1-methyl-N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide (200 mg, 56%). MS (ESI) m/z: 358.2 (M+H+).

후처리

  1. temperaturethe mixture heated at 90° C. for 7 h
  2. temperatureThe mixture was cooled to RT
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified via silica gel chromatography (MeOH/DCM)

출처 및 근거

ORD 기록
ord-0845a84a8fe1403d90b87b4f790ca1ea
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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