Reaktion #306414

Reaktionsgleichung

dimethylacetamide

tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

5-bromo-N,N-dimethylthiazol-2-amine

isopropylmagnesium lithium chloride

→

product

Ausbeute 71.9%

tert-butyl (6-(2-(dimethylamino)thiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

Ausbeute 71.9%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas brought to room temperature
2. 2
   workup.STIRRINGstirred for thirty minutes
3. 3
   workup.STIRRINGThe mixture was stirred at 50° for two hours
4. 4
   Sonstigethen was quenched with saturated ammonium chloride
5. 5
   Sonstigepurified by MPLC chromatography (
6. 6
   Wascheneluted with a gradient of 0 to 10% (1:10:90 NH4OH:MeOH:DCM) in DCM)

Vorschrift

To a solution of 5-bromo-N,N-dimethylthiazol-2-amine (0.73 g, 3.53 mmol) in anhydrous THF (9 mL) was added isopropylmagnesium lithium chloride (1.0 M in THF, 4.8 mL, 4.8 mmol) at −40° C. The solution was stirred for twenty minutes followed by the dropwise addition of zinc chloride (0.5 M in THF, 10 mL, 5.2 mmol). The mixture was brought to room temperature and stirred for thirty minutes followed by the addition of dimethylacetamide (12 mL), Pd2(dba)3, (0.32 g, 0.35 mmol), Q-Phos (0.34 g, 0.56 mmol), and tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (0.29 g, 1.0 mmol). The mixture was stirred at 50° for two hours then was quenched with saturated ammonium chloride and purified by MPLC chromatography (eluted with a gradient of 0 to 10% (1:10:90 NH4OH:MeOH:DCM) in DCM) to yield the product as a light orange solid (0.27 g, 71%).

Quelle