反应详情

The 2-(6-(6-(2,4-difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)propan-2-ol (0.200 g, 0.505 mmol, Example #35) in 1,4-dioxane (1 mL) and 40% methylamine in water (1.5 mL, 17 mmol) was heated in a CEM microwave at about 120° C. for about 55 minutes, (100 psi maximum pressure, 5 min ramp, 300 max watts). The mixture was evaporated and then dissolved in HOAc (2 mL). The solution was stirred at room temperature for about 1 hour then the material was purified by RP-HPLC (Table 1, Method f). The combined fractions were concentrated under reduced pressure to remove the acetonitrile then the solution was basified with saturated aqueous NaHCO3 solution gave an oil. The mixture was extracted with 20% EtOAc in DCM (25 mL) then EtOAc (approx. 15 mL). The combined organics solutions were dried over MgSO4 then filtered and evaporated. The solid was triturated with about 10 mL water then collected by filtration. The material was dissolved in hot acetonitrile (1 mL) then added dropwise to about 10 mL water. The solution was allowed to stand at ambient temperature until a solid formed then the mixture was diluted with water (5 mL). The solid was collected by filtration then dried under vacuum at about 80° C. to give the title compound (0.040 g, 20%); 1H NMR (DMSO-d6) δ 8.15 (d, 1H), 8.10 (d, 1H), 7.76-7.67 (m, 1H), 7.46 (m, 2H), 7.31-7.23 (m, 1H), 6.85-6.80 (m, 1H), 5.66 (s, 1H), 3.72 (s, 3H), 1.78 (s, 6H); LC/MS (Table 1, Method g) Rt=1.65 min; MS m/z: 410.2 (M+H)+.

1. custom(100 psi maximum pressure, 5 min ramp, 300 max watts)
2. customThe mixture was evaporated
3. dissolutiondissolved in HOAc (2 mL)
4. customthe material was purified by RP-HPLC (Table 1, Method f)
5. concentrationThe combined fractions were concentrated under reduced pressure
6. customto remove the acetonitrile
7. customgave an oil
8. extractionThe mixture was extracted with 20% EtOAc in DCM (25 mL)
9. dry with materialThe combined organics solutions were dried over MgSO4
10. filtrationthen filtered
11. customevaporated
12. customThe solid was triturated with about 10 mL water
13. filtrationthen collected by filtration
14. dissolutionThe material was dissolved in hot acetonitrile (1 mL)
15. additionthen added dropwise to about 10 mL water
16. customto stand at ambient temperature until a solid
17. customformed
18. filtrationThe solid was collected by filtration
19. customthen dried under vacuum at about 80° C.