Cesium carbonate → 6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

HRID 40293

Reaktionsgleichung

Reaktionsgleichung von HRID 40293
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[CH3:12])=[N:9][N:10]=2)[N:7]=1.[CH3:23][N:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH3:23][N:24]1[CH:28]=[C:27]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH:11]([C:13]4[CH:14]=[C:15]5[C:20](=[CH:21][CH:22]=4)[N:19]=[CH:18][CH:17]=[CH:16]5)[CH3:12])=[N:9][N:10]=3)[N:7]=2)[CH:26]=[N:25]1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 249687116-(1-(6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

Produkt 1

HCID 248831926-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 53485975CID 53485975KatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A suspension of 6-(1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (106 mg, 342 μmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (142 mg, 684 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(ii)dichloromethane adduct (25 mg, 34 μmol), and cesium carbonate (446 mg, 1369 μmol) in DMF (1 mL) and water (0.5 mL) was sparged for 5 min with argon then heated to 100° C. in an appropriately sealed vial for 30 min. Reaction then partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL). Aqueous further extracted with 9:1 CHCl3/IPA (5 mL) and combined organics dried over MgSO4, concentrated to a solid from toluene, then purified on silica (12 g) eluting with 30>50% of 10% 2M NH3 in MeOH/DCM. 6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline isolated as off white crystals from ACN (1 mL). MS (ESI pos. ion) m/z: 356 (MH+). Calc'd exact mass for C20H17N7: 355.

Aufarbeitung

  1. customwas sparged for 5 min with argon
  2. customReaction
  3. customthen partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL)
  4. extractionAqueous further extracted with 9:1 CHCl3/IPA (5 mL)
  5. dry with materialcombined organics dried over MgSO4
  6. concentrationconcentrated to a solid from toluene
  7. custompurified on silica (12 g)
  8. washeluting with 30>50% of 10% 2M NH3 in MeOH/DCM

Quellen und Nachweise

ORD-Eintrag
ord-b4b857e3fe444b70b3ea0ddd6d928883
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524900B2

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