1-Bromo-3-chloropropane → 1-[3-(4-Butylpiperidin-1-yl)propyl]-6-fluoro-1h-quinolin-2-one

HRID 969426노트

반응식

HRID 969426 반응식
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18]Cl.C([O-])([O-])=O.[K+].[K+].[CH2:26]([CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]>C(OCC)C.CC#N.CCOC(C)=O.CN(C=O)C>[CH2:26]([CH:30]1[CH2:35][CH2:34][N:33]([CH2:16][CH2:17][CH2:18][N:8]2[C:9]3[C:4](=[CH:3][C:2]([F:1])=[CH:11][CH:10]=3)[CH:5]=[CH:6][C:7]2=[O:12])[CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]

참가 물질

10

반응물 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 98340436-Fluoro-1,2-dihydroquinolin-2-oneHCID 132838674-Butylpiperidine

생성물 1

HCID 179560801-[3-(4-Butylpiperidin-1-yl)propyl]-6-fluoro-1h-quinolin-2-one수율 29%

시약·촉매·용매 4

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A 4 mL vial was charged with 6-fluoro-1H-quinolin-2-one (00.56 g, 0.34 mmol), dry DMF (2 mL) and NaH (60% in oil, 0.015 g, 0.34 mmol). The mixture was stirred at rt for 1 h under a N2 atmosphere, and thereafter 1-bromo-3-chloropropane (34 μl, 0.34 mmol) was added and the mixture was then shaken at rt for 20 h. The reaction was diluted with diethyl ether (25 mL) and washed with water (15 mL). The organic phase was washed with water (15 mL) and brine (15 mL), dried over Na2SO4, and concentrated under reduced pressure. The oily residue was diluted with CH3CN (2 mL) and KI (0.083 g, 0.50 mmol), K2CO3 (0.069 g, 0.50 mmol) and 4-butylpiperidine (0.048 g, 0.34 mmol) was added. The mixture was shaken at 50° C. for 72 h and then diluted with EtOAc (25 mL) and washed with water (15 mL). The water phase was extracted (2×25 mL) and the combined organic phase was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by cation-exchange CC followed by flash CC (SiO2; EtOAc/MeOH 4:1) to yield the title compound (0.034 g, 29%). 1H NMR (CD3OD) δ 7.90 (d, J=9.2 Hz, 1H), 7.69 (dd, J=4.0, 8.8 Hz, 1H), 7.50-7.41 (m, 2H), 6.72 (d, J=8.8 Hz, 1 H), 4.41 (t, J=6.8 Hz, 2H), 3.02-2.95 (m, 2H), 2.65-2.60 (m, 2 H), 2.19-2.08 (m, 2H), 1.91-1.82 (m, 4 H), 1.53-1.21 (m, 9H), 0.90 (t, J=7.0 Hz); 13C NMR (CD3OD) δ 169.9, 158.4 (d, J=242 Hz), 139.8 (d, J=3 Hz), 134.4 (d, J=2 Hz), 122.5 (d, J=9 Hz), 121.6, 119.9 (d, J=24 Hz), 116.8 (d, J=8 Hz), 113.9 (d=23 Hz), 54.4, 53.0, 40.1, 34.5, 34.1, 30.1, 28.7, 23.3, 22.6, 13.2; HPLC-MS (ammonium acetate) [M+H]+=345.3.

후처리

  1. stirringthe mixture was then shaken at rt for 20 h
  2. washwashed with water (15 mL)
  3. washThe organic phase was washed with water (15 mL) and brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. additionwas added
  7. stirringThe mixture was shaken at 50° C. for 72 h
  8. washwashed with water (15 mL)
  9. extractionThe water phase was extracted (2×25 mL)
  10. dry with materialthe combined organic phase was dried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by cation-exchange CC

출처 및 근거

ORD 기록
ord-042dea426a70457087670d4dd09bde06
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07307075B2

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