反应详情

温度

65 °C

The 6-(2,4-difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole (0.20 g, 0.65 mmol; prepared using A from 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [prepared according to WO2004110990A2, Example 1, Steps 1-3] with NIS, C with 2-fluoropyridine-5-boronic acid [Asymchem], D with hydrazine) and ethyl 2-oxoacetate (0.65 mL, 9.7 mmol) were dissolved in MeOH (5.0 mL) and heated to about 65° C. for about 1 h. The MeOH was evaporated and then DCM (5 mL) was added followed by iodobenzene diacetate (0.53 g, 1.6 mmol). The reaction was stirred for about 15 min then the DCM was evaporated and the resulting solid was triturated with Et2O. The solid was dissolved in 1,4-dioxane (10 mL) and LiOH (0.060 g, 2.4 mmol) dissolved in water (2 mL) was added drop-wise followed by heating to about 50° C. for about 30 min. The 1,4-dioxane was evaporated and the pH was adjusted to about 1 with 1N HCl. The resulting precipitate was filtered and washed with water (about 10 mL) and dried in a vacuum oven to give the title compound (0.31 g, 80%): LC/MS (Table 1, Method a) Rt=1.88 min; MS m/z: 320.1 (M+H)+.

1. customprepared
2. customThe MeOH was evaporated
3. additionDCM (5 mL) was added
4. customthe DCM was evaporated
5. customthe resulting solid was triturated with Et2O
6. dissolutionThe solid was dissolved in 1,4-dioxane (10 mL)
7. additionwas added drop-wise
8. temperatureby heating to about 50° C. for about 30 min
9. customThe 1,4-dioxane was evaporated
10. filtrationThe resulting precipitate was filtered
11. washwashed with water (about 10 mL)
12. customdried in a vacuum oven