Reaktion #68565

Reaktionsgleichung

4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

tert-butyl 1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethylcarbamate

cesium carbonate

→

tert-butyl 1-(2-chloro-4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl)ethylcarbamate

Lösungsmittel

DMF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas first sparged with argon for 5 min
2. 2
   SonstigeReaction
3. 3
   Sonstigethen partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL)
4. 4
   TrocknenOrganic then dried over MgSO4
5. 5
   Einengenconcentrated
6. 6
   Sonstigepurified on silica (40 g)
7. 7
   Wascheneluting with isocratic 4% of 2M NH3 in MeOH/DCM

Vorschrift

A suspension of 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (180 mg, 527 μmol), tert-butyl 1-(2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethylcarbamate (302 mg, 790 μmol), dichloro[1,1′bis(diphenylphoshino)ferrocene]palladium(ii)dichloromethane adduct (77.1 mg, 105 μmol), cesium carbonate (686 mg, 2107 μmol) in DMF (2 mL) and water (0.4 mL) was first sparged with argon for 5 min then heated to 100° C. with stirring. 2:20 pm After 10 min, LCMS suggests >95% conversion. Reaction then partitioned between 9:1 CHCl3/IPA (20 mL) and 1M NaOH (5 mL). Organic then dried over MgSO4, concentrated, and purified on silica (40 g) eluting with isocratic 4% of 2M NH3 in MeOH/DCM. MS (ESI pos. ion) m/z: 561 (MH+). Calc'd exact mass for C29H29ClN6O4: 560.

Quelle