Sodium Iodide → 1-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one

HRID 1986856노트

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HRID 1986856 반응식
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:16])=[C:12]([F:15])[CH:13]=2)[CH2:8][CH2:7][C:6]1=[O:17].[CH:18]1([CH2:21][O:22][CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:20][CH2:19]1.[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CC#N.CN(C=O)C.O>[CH:18]1([CH2:21][O:22][CH:23]2[CH2:28][CH2:27][N:26]([CH2:2][CH2:3][CH2:4][N:5]3[C:14]4[C:9](=[CH:10][C:11]([F:16])=[C:12]([F:15])[CH:13]=4)[CH2:8][CH2:7][C:6]3=[O:17])[CH2:25][CH2:24]2)[CH2:19][CH2:20]1

참가 물질

7

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 171780104-(Cyclopropylmethoxy)piperidineHCID 179561691-(3-Chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one

생성물 1

HCID 115381241-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one수율 81.5%

시약·촉매·용매 2

HCID 962Water용매HCID 21891449acetonitrile N,N-dimethylformamide용매

반응 조건

온도
50 °C

실험 절차

A 4 ml vial was charged with 1-(3-chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one (78 mg, 0.30 mmol), 4-cyclopropylmethoxypiperidine (145LH49) (42 mg, 0.27 mmol), NaI (75 mg, 0.50 mmol), and K2CO3 (69 mg, 0.50 mmol) in CH3CN/DMF (1 ml, 50:50). The reaction was shaken at 50° C. for 3 days and the reaction was poured into water and extracted with EtOAc. The organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The oily residue was purified by ion-exchange column chromatography followed by flash column chromatography (SiO2; EtOAc) to yield the title compound as an oil (83 mg, 0.22 mmol, 81%). 1H NMR (CDCl3) d 6.90 (dd, J=6.8, 12.0 Hz, 1H), 6.82-6.75 (m, 1H), 3.73 (t, J=7.2 Hz, 2H), 3.22-3.13 (m, 1H), 3.11 (d, J=6.8 Hz, 2H), 2.69-2.54 (m, 4H), 2.47-2.41 (m, 2H), 2.23-2.17 (m, 2H), 2.01-1.91 (m, 2H), 1.78-1.58 (m, 4H), 1.52-1.40 (m, 2H), 0.94-0.82 (m, 1H), 0.44-0.28 (m, 2H), 0.06-(−)0.03 (m, 2H); 13C NMR (CDCl3) d 166.4, 146.1 (dd, J=13, 243 Hz), 142.3 (dd, J=13, 243 Hz), 133.3 (dd, J=3, 8 Hz), 119.4 (dd, J=2, 5 Hz), 113.3 (d, J=18 Hz), 102.0 (d, J=22 Hz), 71.5 (br), 69.5, 52.2, 48.3, 38.0, 28.6, 28.2, 21.9, 21.7, 7.9, 0.0; HPLC-MS (ammonium acetate) [M+H]+=379.29.

후처리

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe oily residue was purified by ion-exchange column chromatography

출처 및 근거

ORD 기록
ord-6aee9179f91a4668b9ad8eebd1b45ee8
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07550459B2

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