Reaktion #68571

Reaktionsgleichung

6-(1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

cesium carbonate

→

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

Lösungsmittel

DMF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas sparged for 5 min with argon
2. 2
   SonstigeReaction
3. 3
   Sonstigethen partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL)
4. 4
   ExtraktionAqueous further extracted with 9:1 CHCl3/IPA (5 mL)
5. 5
   Trocknencombined organics dried over MgSO4
6. 6
   Einengenconcentrated to a solid from toluene
7. 7
   Sonstigepurified on silica (12 g)
8. 8
   Wascheneluting with 30>50% of 10% 2M NH3 in MeOH/DCM

Vorschrift

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.

Quelle