Cesium carbonate → HCID 90410005, 화합물

HRID 626599노트

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HRID 626599 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.[CH2:18]([N:25]1[CH2:30][CH2:29][N:28]([C:31]([NH2:33])=[O:32])[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH2:18]([N:25]1[CH2:26][CH2:27][N: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])[CH2:29][CH2:30]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 8518614-benzylpiperazine-1-carboxamideHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

생성물 1

HCID 90410005HCID 90410005, 화합물수율 66.5%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

A suspension of Example A1 (0.5 g, 1.987 mmol), 4-benzylpiperazine-1-carboxamide (0.741 g, 3.38 mmol), cesium carbonate (0.971 g, 2.98 mmol) and X-Phos (0.047 g, 0.099 mmol) in dioxane (20 mL) was purged 5 min with Ar. To the reaction mixture was added Pd2 dba3 (0.055 g, 0.060 mmol) and it was then heated to 120° C. After 16 h, the reaction was cooled to RT, diluted with EtOAc (100 mL) and filtered through diatomaceous earth. The filter cake was washed with additional EtOAc and the combined filtrates concentrated to afford crude product. This was purified by silica gel chromatography (0-8% MeOH/DCM) to afford 4-benzyl-N-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)piperazine-1-carboxamide (0.574 g, 66%). 1H NMR (400 MHz, DMSO-d6): δ 9.41 (s, 1H), 8.56 (d, J=2.8 Hz, 1H), 8.40 (d, J=8.9 Hz, 1H), 8.23 (d, J=5.7 Hz, 1H), 7.94 (dd, J=8.9, 2.8 Hz, 1H), 7.55 (d, J=2.3 Hz, 1H), 7.30-7.29 (m, 5H), 6.79 (dd, J=5.7, 2.4 Hz, 1H), 3.47 (s, 2H), 3.43 (t, J=4.7 Hz, 4H), 2.32 (t, J=4.7 Hz, 4H); MS (ESI) m/z: 435.2 (M+H+).

후처리

  1. temperaturethe reaction was cooled to RT
  2. filtrationfiltered through diatomaceous earth
  3. washThe filter cake was washed with additional EtOAc
  4. concentrationthe combined filtrates concentrated
  5. customto afford crude product
  6. customThis was purified by silica gel chromatography (0-8% MeOH/DCM)

출처 및 근거

ORD 기록
ord-bba4116e947240ffa3b5e64c92c2d326
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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