Sodium Hydroxide → 6-(4-{2-[(3,5-Dimethyl-isoxazol-4-ylmethyl)-amino]-ethyl}-phenoxy)-nicotinamide

HRID 492311

Reaktionsgleichung

Reaktionsgleichung von HRID 492311
C(=O)(O)[O-].[Na+].Cl[CH2:7][C:8]1[C:9]([CH3:14])=[N:10][O:11][C:12]=1[CH3:13].[NH2:15][CH2:16][CH2:17][C:18]1[CH:33]=[CH:32][C:21]([O:22][C:23]2[CH:31]=[CH:30][C:26]([C:27]([NH2:29])=[O:28])=[CH:25][N:24]=2)=[CH:20][CH:19]=1.[OH-].[Na+]>CN(C)C=O>[CH3:14][C:9]1[C:8]([CH2:7][NH:15][CH2:16][CH2:17][C:18]2[CH:33]=[CH:32][C:21]([O:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([NH2:29])=[O:28])=[CH:25][N:24]=3)=[CH:20][CH:19]=2)=[C:12]([CH3:13])[O:11][N:10]=1

Komponenten

6

Edukt 4

HCID 14798Sodium HydroxideHCID 88246Isoxazole, 4-(chloromethyl)-3,5-dimethyl-HCID 516892Sodium BicarbonateHCID 597300176-[4-(2-Amino-ethyl)-phenoxy]-nicotinamide

Produkt 1

HCID 597300046-(4-{2-[(3,5-Dimethyl-isoxazol-4-ylmethyl)-amino]-ethyl}-phenoxy)-nicotinamideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Add sodium bicarbonate (0.0481 g, 0.573 mmol) to a stirred solution of 4-(chloromethyl)-3,5-dimethylisoxazole (0.054 mL, 0.435 mmol), and 6-[4-(2-amino-ethyl)-phenoxy]-nicotinamide (0.1004 g, 0.390 mmol) in dimethylformamide (4 mL). Heat the reaction to reflux under nitrogen for 4 h. Cool to room temperature, pour the reaction mixture into 1 N sodium hydroxide (50 mL), extract with diethyl ether (3× 50 mL), dry the extracts over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. The crude product is purified by flash chromatography on silica gel eluting with 0.8% concentrated ammonium hydroxide/8% ethanol/chloroform to yield 0.0843 g (59%) of 6-(4-{2-[(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-ethyl}-phenoxy)-nicotinamide: mass spectrum (ion spray): m/z 367.1 (M+1); 1H NMR (CDCl3): 8.57 (dd, 1H), 8.16 (dd, 1H), 7.26-7.22 (m, 4H), 7.09-7.05 (m, 2H), 6.96 (d, 1H), 3.54 (s, 2H), 2.88-2.79 (m, 4H), 2.33 (s, 3H), 2.20 (s, 3H), 1.50 (br s, 1H).

Aufarbeitung

  1. temperatureHeat
  2. customthe reaction
  3. temperatureto reflux under nitrogen for 4 h
  4. extractionextract with diethyl ether (3× 50 mL)
  5. dry with materialdry the extracts over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate on a rotary evaporator
  8. customto give the crude product
  9. customThe crude product is purified by flash chromatography on silica gel eluting with 0.8% concentrated ammonium hydroxide/8% ethanol/chloroform

Quellen und Nachweise

ORD-Eintrag
ord-69c2f0bb3d0c44c1bd7f211943a455e8
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531557B2

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