Water → (S)-6-Chloro-2-methyl-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 407659Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 407659
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C@@H:18]3[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[O:24]1[CH2:27][C:26](=O)[CH2:25]1.[BH3-]C#N.[Na+].O>CO.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:26]4[CH2:27][O:24][CH2:25]4)[CH2:19][C@@H:18]3[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86683945(S)-6-Chloro-2-methyl-4-(5-(2-methylpiperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

Produkt 1

HCID 86683946(S)-6-Chloro-2-methyl-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-oneAusbeute 75,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3007855ZincchlorideKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of 117b (2.3 g, 6.8 mmol), oxetan-3-one (1.4 g, 20.0 mmol), NaBH3CN (620 mg, 10 mmol), and zinc chloride (1.36 g, 10 mmol) in methanol (20 mL) was stirred at 50° C. for 3 hours. The mixture was added to water (40 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane three times. The combined organic layer was dried and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 117c (2.0 g, 75%). MS-ESI: [M+H]+ 391.2.

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. extractionThe residue was extracted with dichloromethane three times
  3. customThe combined organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 50:1 dichloromethane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-ad3db01db40e47b99ab8a43282354123
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754077B2

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