반응 #626981

반응 방정식

2-(4-methyl-3-pivalamidophenyl)imidazo[1,2-b]pyridazin-6-ylboronic acid

4-bromo-3-(trifluoromethyl)benzonitrile

K2CO3

2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl

→

desired title compound

수율 48.3%

N-(5-(6-(4-cyano-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide

수율 48.3%

용매

isopropanol water

반응 조건

후처리

1. 1
   기타The mixture is degassed
2. 2
   기타by bubbling N2 through and
3. 3
   온도The mixture is then cooled
4. 4
   여과filtered through celite,
5. 5
   농축concentrated
6. 6
   기타purified by silica gel chromatography (0-100% EtOAc in CH2Cl2)
7. 7
   여과filtered
8. 8
   농축concentrated

실험 절차

A 200 mL flask is charged with 2-(4-methyl-3-pivalamidophenyl)imidazo[1,2-b]pyridazin-6-ylboronic acid (11.4 g, 0.0325 mol), 4-bromo-3-(trifluoromethyl)benzonitrile (10.16 g, 0.04 mol), K2CO3 (8.98 g, 0.065 mol), palladium acetate (0.510 g, 2.28 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (1.868 g, 4.55 mmol) and a solution of isopropanol-water (3:1, 80 mL). The mixture is degassed by bubbling N2 through and heated at 90° C. for 5 hours. The mixture is then cooled and filtered through celite, concentrated and purified by silica gel chromatography (0-100% EtOAc in CH2Cl2). The desired fractions are combined and stirred for 24 hours with QuadraSil MP (a mercaptopropyl bound silica gel, 20 g) to scavenge the palladium, filtered and concentrated to give desired title compound (7.5 g). LCMS (m/z)=478.6 [M+H]+, tR=2.97 min.

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