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

HRID 1191465ノート

反応式

HRID 1191465 の反応式
[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]

参加物

10

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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, 1H), 4.41 (t, J=6.8 Hz, 2H), 3.02-2.95 (m, 2H), 2.65-2.60 (m, 2H), 2.19-2.08 (m, 2H), 1.91-1.82 (m, 4H), 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.

後処理

  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

出典と根拠

ORDレコード
ord-3f1b0cd1d240445f84c314b485bcdac4
出典データセット
uspto-grants-2014_03
特許番号
US08680115B2

反応ノート

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