تفاعل #156461

معادلة التفاعل

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

المذيبات

acetic acid

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONintroduced in 4 microwave reactors
2. 2
   workup.ADDITIONwere then added into each reactor
3. 3
   أخرىirradiations 5 min
4. 4
   أخرىat 150° C
5. 5
   استخلاصextracted twice with EtOAc
6. 6
   غسيلwashed with brine
7. 7
   تجفيفdried over Na2SO4
8. 8
   أخرىthe solvent was removed
9. 9
   أخرىThe 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
    أخرىwere evaporated
12. 12
    أخرىthe residue was dried under vacuum

الإجراء التجريبي

(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).

المصدر