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

HRID 33834

反応式

HRID 33834 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 78373Dimethylformamide dimethyl acetal溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-8555a74987ca4c78a29f919bd5a12ab0
出典データセット
uspto-grants-2008_09
特許番号
US07429665B2

関連ノート

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