N-Hydroxyacetamidine → N-(1-{[2-Chloro-5-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

HRID 1946385Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1946385
[C:1](=[N:4][OH:5])([NH2:3])[CH3:2].[O-]CC.[Na+].[Cl:10][C:11]1[CH:20]=[CH:19][C:14]([C:15](OC)=O)=[CH:13][C:12]=1[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28]([C:30]2[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=2[F:37])=[O:29])=[N:23]1>C(O)C>[Cl:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]2[O:5][N:4]=[C:1]([CH3:2])[N:3]=2)=[CH:13][C:12]=1[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:29])[C:30]2[C:31]([F:37])=[CH:32][CH:33]=[CH:34][C:35]=2[F:36])=[N:23]1

Komponenten

5

Edukt 3

HCID 30926N-HydroxyacetamidineHCID 2723922Sodium ethoxideHCID 59547941Methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate

Produkt 1

HCID 59547977N-(1-{[2-Chloro-5-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of acetamide oxime (89 mg, 1.20 mmol, GFS chemicals) in ethanol (2 ml) was added 4A activated molecular sieves (418 mg) (pre-dried in the oven overnight) and then 21% sodium ethoxide in ethanol (0.2 ml, 0.536 mmol, Alfa Aesar). To the reaction mixture was added methyl 4-chloro-3-[(3-{[(2,6-difluorophenyl)carbonyl]amino}-1H-pyrazol-1-yl)methyl]benzoate (for a preparation see Intermediate 23)(105 mg, 0.259 mmol). The reaction was heated to reflux (100° C.) and stirred for 3 h under nitrogen. The reaction mixture was evaporated in vacuo and the residue dissolved in methanol (0.5 ml) and filtered through a hydrophobic frit. The residue was dissolved with DMSO (0.5 ml) and the sample was purified by MDAP on Sunfire C18 column using Acetonitrile-Water with a Formic acid modifier (Method B). The solvent was evaporated in vacuo to give the title compound as a white gum (6.1 mg);

Aufarbeitung

  1. temperatureThe reaction was heated
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue dissolved in methanol (0.5 ml)
  4. filtrationfiltered through a hydrophobic frit
  5. dissolutionThe residue was dissolved with DMSO (0.5 ml)
  6. customthe sample was purified by MDAP on Sunfire C18 column
  7. customThe solvent was evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d0f332b905cd402c8c7614d7c25838a7
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399436B2

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