Sodium hydride → HCID 86686831, Verbindung

HRID 402930Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 402930
Br[C:2]1[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH:12]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:22]=[CH:23][C:24]([NH2:27])=[N:25][CH:26]=2)[CH2:17][CH2:16]1)([CH3:14])[CH3:13].[H-].[Na+]>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([NH:27][C:24]2[CH:23]=[CH:22][C:21]([N:18]3[CH2:19][CH2:20][N:15]([CH:12]([CH3:14])[CH3:13])[CH2:16][CH2:17]3)=[CH:26][N:25]=2)[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 434619445-(4-(Propan-2-yl)piperazin-1-yl)pyridin-2-amineHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

Produkt 1

HCID 86686831HCID 86686831, VerbindungAusbeute 24,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (200 mg, 862 μmol, Eq: 0.95) and 5-(4-isopropylpiperazin-1-yl)pyridin-2-amine (200 mg, 908 μmol, Eq: 1.00) in DMF (10.0 ml) was cooled to 0° C. To this reaction mixture was added sodium hydride (116 mg, (60% in mineral oil), 2.9 mmol, Eq: 3.2). The reaction was allowed to stir at 0° C. for 10 min then allowed to warm to room temperature and stir 18 h. The reaction mixture was quenched with sat. NaHCO3 (aq) and diluted with water and EtOAc. The organic layer was separated and the aqueous phase was extracted with EtOAc. The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 20% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give a residue that was placed under high vacuum for 18 h to afford (6-chloro-imidazo[1,2-b]pyridazin-8-yl)-[5-(4-isopropyl-piperazin-1-yl)-pyridin-2-yl]-amine (78 mg, 23%). LC/MS-ESI observed [M+H]+ 372.

Aufarbeitung

  1. temperatureto warm to room temperature
  2. stirringstir 18 h
  3. customThe reaction mixture was quenched with sat. NaHCO3 (aq)
  4. additiondiluted with water and EtOAc
  5. customThe organic layer was separated
  6. extractionthe aqueous phase was extracted with EtOAc
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography (silica gel, 0% to 20% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)
  10. customto give a residue that
  11. waitwas placed under high vacuum for 18 h

Quellen und Nachweise

ORD-Eintrag
ord-3861c5b0e19e4ee39a4aa499062e70a4
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08742098B2

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