반응 #626982

반응 방정식

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

hydroxylamine hydrochloride

Et3N

→

desired title product

수율 81.8%

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

수율 81.8%

용매

ethanol

반응 조건

후처리

1. 1
   농축The mixture is concentrated onto celite
2. 2
   기타purified by silica gel chromatography (eluted by 0 to 100% of 10:1 EtOAc:MeOH in CH2Cl2)
3. 3
   기타recrystallization with isopropanol
4. 4
   workup.ADDITIONThis solid product is then added to a stirred mixture of saturated aqueous NaHCO3 and EtOAc
5. 5
   여과Solid suspension is collected by filtration
6. 6
   추출The liquid portion is back extracted with EtOAc
7. 7
   건조dried with Na2SO4
8. 8
   농축concentrated
9. 9
   기타to afford additional solid product
10. 10
    기타The combined solid product is dried on a lyophilizer overnight
11. 11
    기타recrystallized from hot Isopropanol

실험 절차

A 500-mL flask is charged with N-(5-(6-(4-cyano-2-(trifluoromethyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)-2-methylphenyl)pivalamide (7.496 g, 0.0157 mol), hydroxylamine hydrochloride (6.55 g, 0.0942 mol), Et3N (15.32 mL, 0.1099 mol), ethanol (82.5 mL) and the resulting mixture is stirred for 2 hours at 80° C. The mixture is concentrated onto celite and purified by silica gel chromatography (eluted by 0 to 100% of 10:1 EtOAc:MeOH in CH2Cl2). The isolated solid material (over 20 g) contains triethylamine and hydroxylamine salts, and the salts stay even after attempted recrystallization with isopropanol. This solid product is then added to a stirred mixture of saturated aqueous NaHCO3 and EtOAc. Solid suspension is collected by filtration. The liquid portion is back extracted with EtOAc and the organic layers are combined, dried with Na2SO4, concentrated to afford additional solid product. The combined solid product is dried on a lyophilizer overnight, recrystallized from hot Isopropanol to afford the desired title product (6.56 g). LCMS (m/z)=511.6 [M+H]+, tR=2.49 min.

출처