Cesium carbonate → 1-[5-Chloro-8-(4-cyclobutylpiperazin-1-yl)quinolin-7-yl]ethanone

HRID 1192619노트

반응식

HRID 1192619 반응식
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.Cl.[CH:25]1([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:32]2[CH2:33][CH2:34][N:29]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[CH2:30][CH2:31]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 451567991-Cyclobutylpiperazine dihydrochlorideHCID 58368658HCID 58368658, 화합물

생성물 1

HCID 583685411-[5-Chloro-8-(4-cyclobutylpiperazin-1-yl)quinolin-7-yl]ethanone수율 59.2%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 634876Binap, (A+-)-촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), 1-cyclobutylpiperazine dihydrochloride (0.087 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.44 g, 1.4 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4 and and evaporated to dryness. The residue was purified on silica gel (eluting with 0 to 10% methanol in dichloromethane) to give the desired product (69.2 mg, 59%). LCMS calculated for C19H23ClN3O (M+H)+: m/z 344.2; Found: 344.1

후처리

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe residue was purified on silica gel (eluting with 0 to 10% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-8b09538581da49dcb0cd289e540b1243
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680108B2

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