반응 #156461

반응 방정식

NaOH

Iodide

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethanol

H3PO2

→

title compound

(rac)-3-[1-(6-Fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

용매

acetic acid

반응 조건

후처리

1. 1
   workup.ADDITIONintroduced in 4 microwave reactors
2. 2
   workup.ADDITIONwere then added into each reactor
3. 3
   기타irradiations 5 min
4. 4
   기타at 150° C
5. 5
   추출extracted twice with EtOAc
6. 6
   세척washed with brine
7. 7
   건조dried over Na2SO4
8. 8
   기타the solvent was removed
9. 9
   기타The residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 30 min)
10. 10
    workup.ADDITIONThe collected fractions containing product
11. 11
    기타were evaporated
12. 12
    기타the residue was dried under vacuum

실험 절차

(rac)-6-Chloro-3-[1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (rac)-1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)-ethanol (Stage 278.2, 2 g, 5.78 mmol) was dissolved in acetic acid (80 mL) and introduced in 4 microwave reactors. Iodide (1.84 g×4, 29 mmol), followed by H3PO2 50% (2.36 mL×4, 87 mmol) were then added into each reactor. Then they were submitted to microwave irradiations 5 min at 150° C. After combination, it was basified by a 2.5 M NaOH solution and extracted twice with EtOAc. The organics were joined and washed with brine, dried over Na2SO4 and the solvent was removed. The residue was purified by flash chromatography (CombiFlash® Companion System®, with 120 g RediSep® silica gel column, DCM/MeOH=100:0->94:6 in 30 min). The collected fractions containing product were evaporated and the residue was dried under vacuum to afford the title compound (tR 1.15 min (conditions 2), MH+=330).

출처