反应详情

温度

150 °C

Iodine (50.8 mg, 0.2 mmol) and H3PO2 (0.11 mL of a 50% aqueous solution, 1.0 mmol) were added to a solution of (rac)-Imidazo[1,2-a]pyridin-6-yl-[6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-methanol (Example 9, 34.5 mg, 0.1 mmol) in acetic acid (0.5 mL). The RM was heated at 150° C. for 1 h. The RM was diluted with water and extracted with EtOAc. The organic layer was separated and washed with 10% Na2CO3-sol then dried on Na2SO4, filtered and concentrated. Combined aqueous layers were completely neutralized and again extracted with DCM containing little MeOH. Organic layers were evaporated and both crudes from the two extractions were purified together by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5->80:20). The fractions containing the product were evaporated and the residue taken in EtOAc and pentane, filtered and dried under high vacuum to afford the title compound as beige crystals (tR 2.70 min (conditions 3), MH+=330.2, 1H-NMR in DMSO-d6: 8.58 (s, 1H); 8.44 (s, 1H); 8.12 (s, 1H); 8.08 (d, 1H); 7.90 (s, 1H); 7.62 (s, 1H); 7.54-7.44 (m, 3H); 7.22 (d, 1H); 4.31 (s, 2H); 3.90 (s, 3H)).

1. extractionextracted with EtOAc
2. customThe organic layer was separated
3. washwashed with 10% Na2CO3-sol
4. customthen dried on Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. extractionagain extracted with DCM containing little MeOH
8. customOrganic layers were evaporated
9. extractionboth crudes from the two extractions
10. customwere purified together by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=95:5->80:20)
11. additionThe fractions containing the product
12. customwere evaporated
13. filtrationpentane, filtered
14. customdried under high vacuum