Acetic Acid → 2-[4-(4-Pyridin-4-yl-isoxazol-5-yl)-phenoxymethyl]-quinoline

HRID 33834

반응식

HRID 33834 반응식
[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)=[CH:12][CH:11]=2)=O)=[CH:3][CH:2]=1.Cl.[OH:29][NH2:30].[C:31](O)(=O)C.C(=O)(O)[O-].[Na+]>COC(N(C)C)OC>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:31]=[N:30][O:29][C:8]=2[C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)=[CH:12][CH:11]=2)=[CH:3][CH:2]=1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 336797272-(Pyridin-4-yl)-1-(4-(quinolin-2-ylmethoxy)phenyl)ethan-1-one

생성물 1

HCID 116537552-[4-(4-Pyridin-4-yl-isoxazol-5-yl)-phenoxymethyl]-quinoline수율 45%

시약·촉매·용매 1

HCID 78373Dimethylformamide dimethyl acetal용매

실험 절차

2-pyridin-4-yl-1-[4-(quinolin-2-ylmethoxy)-phenyl]-ethanone (200 mg, 0.56 mmole) was heated at reflux in dimethoxymethyl-dimethyl amine (1 ml) for 1 h and concentrated. The crude product was dissolved in methanol/water (3:1, 4 ml) and hydroxyl amine hydrochloride (43 mg, 1.1 eq.) was added. After 1 h, acetic acid was added (0.016 ml) and the reaction was heated at reflux for 1h. Cooled to ambient temperature poured into saturated sodium bicarbonate, extracted with methylene chloride, dried magnesium sulfate, filtered and concentrated. Biotage MPLC was run on a 25S column elution with 3% methanol/1% ammonium hydroxide/ethyl acetate 50% in hexanes to provide the title compound as a tan solid (94 mg, 45%). 1H NMR (400 MHz, CDCl3) δ 8.59(dd, J=6.2, 1.7 Hz, 2 H), 8.36 (s, 1H), 8.20 (d, J=8.3 Hz, 1H), 8.07 (d, J=8.7 Hz, 1 H), 7.82 (d, J=9.1 Hz, 1H), 7.73 (dt, J=7.1, 1.7 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.54 (m, 3H), 7.28 (d, J=4.2 Hz, 2H) 7.05 (d, J=9.1, 2H), 5.40 (s, 2H); MS: (M+H m/z=380.2).

후처리

  1. concentrationconcentrated
  2. dissolutionThe crude product was dissolved in methanol/water (3:1, 4 ml)
  3. temperaturethe reaction was heated
  4. temperatureat reflux for 1h
  5. extractionextracted with methylene chloride, dried magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washBiotage MPLC was run on a 25S column elution with 3% methanol/1% ammonium hydroxide/ethyl acetate 50% in hexanes

출처 및 근거

ORD 기록
ord-8555a74987ca4c78a29f919bd5a12ab0
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07429665B2

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