Sodium hydride → 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methoxy-pyridazin-3-yl)-amide

HRID 1469385Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1469385
[CH3:1][O:2][C:3]1[N:8]=[N:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[H-].[Na+].[N+](C1C=CC([O:21][C:22]([N:24]2[CH2:27][CH:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])=[CH:31][N:30]=3)[CH2:25]2)=O)=CC=1)([O-])=O>CN(C=O)C>[CH3:1][O:2][C:3]1[N:8]=[N:7][C:6]([NH:9][C:22]([N:24]2[CH2:25][CH:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])=[CH:31][N:30]=3)[CH2:27]2)=[O:21])=[CH:5][CH:4]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 816736-Methoxypyridazin-3-amineHCID 580731093-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester

Produkt 1

HCID 442192123-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methoxy-pyridazin-3-yl)-amideAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of 6-Methoxy-pyridazin-3-ylamine (39 mg, 0.31 mmol, [Cas. No. 7252-84-8]) in DMF (3 mL) at 0° C. was added sodium hydride (20 mg, 0.5 mmol, 60% disp. in mineral oil). After stirring at 0° C. for 15 min. a solution of 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester (102 mg, 0.25 mmol) in DMF (4 mL) was added dropwise. After stirring for 16 hrs at ambient temperature the reaction mixture was concentrated in vacuo, diluted with ethyl acetate (50 mL) and washed sequentially with sat. aqueous sodium hydrogen carbonate solution (2×50 mL) then sat. sodium chloride solution (50 mL). Mixture dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo and the residue was purified by flash chromatography (ethyl acetate) to give the title compound (35 mg, 37%)

Aufarbeitung

  1. additionwas added dropwise
  2. concentrationwas concentrated in vacuo
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed sequentially with sat. aqueous sodium hydrogen carbonate solution (2×50 mL)
  5. dry with materialMixture dried over magnesium sulphate
  6. filtrationfiltered
  7. customFiltrate solvents were removed in vacuo
  8. customthe residue was purified by flash chromatography (ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-ac0396eadfae46ef98b1c079f8a9da17
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09006269B2

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