Sodium hydride → 1-Benzyl-3-[3-(N,N-dimethylaminomethyl)-1,2,4-oxadiazol-5-yl]indazole

HRID 1711612

Reaktionsgleichung

Reaktionsgleichung von HRID 1711612
Cl.[NH2:2]O.[Na].[CH3:5][N:6]([CH2:8][C:9]#[N:10])[CH3:7].[H-].[Na+].C[O:14][C:15]([C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]=1)=O>CO>[CH2:26]([N:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([C:15]2[O:14][N:2]=[C:9]([CH2:8][N:6]([CH3:7])[CH3:5])[N:10]=2)=[N:18]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Komponenten

7

Edukt 5

HCID 24758Sodium hydrideHCID 61237DimethylaminoacetonitrileHCID 443297Hydroxyamine hydrochlorideHCID 5360545SodiumHCID 10563690methyl 1-benzyl-1H-indazole-3-carboxylate

Produkt 1

HCID 672046081-Benzyl-3-[3-(N,N-dimethylaminomethyl)-1,2,4-oxadiazol-5-yl]indazoleAusbeute 48,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Hydroxylamine hydrochloride (124 g 17.8 mmol) was added to a solution of sodium (0.64 g, 26 mmol) in MeOH (100 mL). The reaction mixture was stirred at 25° C. for 15 min then dimethylaminoacetonitrile (1.5 g, 17.8 mmol) in MeOH (5 mL) was added and the reaction mixture stirred at 25° C. for a further 5 days. The solid was removed by filtration and the liquid concentrated under reduced pressure. The crude material was taken up in dry THF (100 mL) and sodium hydride (0.114 g, 60%, 2.86 mmol) was added and the reaction mixture was heated to 50° C. 1-Benzylindazole-3-carboxylic acid methyl ester (0.25 g, 0.938 mmol) was added and the reaction mixture was heated at reflux for 4 h. The THF was removed under reduced pressure and the residue partitioned between chloroform (100 mL) and H2O (100 mL). The chloroform layer was separated and the aqueous layer was further extracted with 2×100 mL of chloroform. The combined extracts were dried (MgSO4) and concentrated under reduced pressure. The crude compound was purified by flash chromatography using chloroform/MeOH (97.5:2.5) to afford the title compound (0.151 g, 48%) as a yellow solid. Mp 93-95° C. 1H NMR (300 MHz, CDCl3) ppm 2.40 (s, 6H), 3.77 (s, 2H), 5.68 (s, 2H), 7.19-7.37 (m, 8H), 8.27-8.30 (m, 211). MS(FAB) m/z 334 [M+H]+. HRMS Calcd. for C19H20N5O: 334.1668. Found: 334.1655 [M+H]+.

Aufarbeitung

  1. stirringthe reaction mixture stirred at 25° C. for a further 5 days
  2. customThe solid was removed by filtration
  3. concentrationthe liquid concentrated under reduced pressure
  4. temperaturethe reaction mixture was heated to 50° C
  5. temperaturethe reaction mixture was heated
  6. temperatureat reflux for 4 h
  7. customThe THF was removed under reduced pressure
  8. customthe residue partitioned between chloroform (100 mL) and H2O (100 mL)
  9. customThe chloroform layer was separated
  10. extractionthe aqueous layer was further extracted with 2×100 mL of chloroform
  11. dry with materialThe combined extracts were dried (MgSO4)
  12. concentrationconcentrated under reduced pressure
  13. customThe crude compound was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-007f539eb681448d99a98e3451dc34c9
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07790761B2

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