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

HRID 1170272

Reaktionsgleichung

Reaktionsgleichung von HRID 1170272
[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.[NH2:29][OH: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:29][O:30][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

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 78373Dimethylformamide dimethyl acetalLösungsmittel

Versuchsvorschrift

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 hydroxylamine 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 1 h. 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, 2H), 8.36 (s, 1H), 8.20 (d, J=8.3 Hz, 1H), 8.07 (d, J=8.7 Hz, 1H), 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).

Aufarbeitung

  1. concentrationconcentrated
  2. dissolutionThe crude product was dissolved in methanol/water (3:1, 4 ml)
  3. temperaturethe reaction was heated
  4. temperatureat reflux for 1 h
  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

Quellen und Nachweise

ORD-Eintrag
ord-bb6faa3be947481e8922a93dd793afd6
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07825254B2

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