반응 #626980

반응 방정식

N-[5-(6-chloroimidazo[2,1-f]pyridazin-2-yl)-2-methyl-phenyl]-2,2-dimethyl-propanamide

bis(pinacolato)diboron

potassium acetate

→

desired product

수율 54.0%

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

수율 54.0%

용매

dioxane

반응 조건

후처리

1. 1
   온도The reaction mixture is cooled
2. 2
   농축concentrated
3. 3
   workup.ADDITIONadded to an aqueous NaOH solution (150 mL, 3 M)
4. 4
   추출then extracted with EtOAc (300 mL)
5. 5
   세척Organic layers are washed with the NaOH solution (150 mL, 3 M)
6. 6
   세척washed twice with ether
7. 7
   온도This heterogeneous solution is cooled in the freezer for 2 hours
8. 8
   여과the solids are collected by filtration

실험 절차

A suspension of N-[5-(6-chloroimidazo[2,1-f]pyridazin-2-yl)-2-methyl-phenyl]-2,2-dimethyl-propanamide (15.43 g 0.045 mol), bis(pinacolato)diboron (17.14 g, 0.0675 mol), potassium acetate (8.833 g, 0.09 mol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2.305 g, 3.15 mmol) in dioxane (153 mL) is heated at 90° C. for 16 hours. The reaction mixture is cooled, concentrated, added to an aqueous NaOH solution (150 mL, 3 M). The mixture is stirred for 1 hour then extracted with EtOAc (300 mL). Organic layers are washed with the NaOH solution (150 mL, 3 M). The aqueous portions are combined, washed twice with ether, and the aqueous pH is lowered to 5 with an aqueous HCl solution (6 M) to cause solid formation. This heterogeneous solution is cooled in the freezer for 2 hours, the solids are collected by filtration to give the desired product (8.56 g). The resulting aqueous solution is back extracted with EtOAc, combined with earlier organic portions and filtered through celite. The combined organic layer is dried, concentrated and taken up into an aqueous HCl solution (0.5 M). The solid product formed is collected by filtration and combined with the earlier batch, to afford a total 10.16 g of the desired title compound. LCMS (m/z)=353.5 [M+H]+, tR=2.04 min.

출처