反应详情

To a mixture of 3-(1-methyl-5-nitro-1H-pyrazol-3-yl)-1,2,4-oxadiazole (2.0 g, 10.3 mmol) and ammonium chloride (7.68 g, 143 mmol) in a 1:1 mixture of THF (32 mL)/MeOH (32 mL) at 0° C. was added zinc dust (9.38 g, 143 mmol) portionwise. The ice bath was removed after about 10 min and the reaction was stirred at ambient temperature for about 1 h. The reaction mixture was filtered through a pad of Celite® rinsing with MeOH (30 mL) and then concentrated under reduced pressure. The crude material was partitioned between DCM (20 mL) and water (10 mL). The organic layer was separated and the aqueous layer was back extracted with DCM (20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The aqueous layer was acidified using 1 N HCl to about pH 3 and DCM (50 mL) was added. The organic layer was separated dried over MgSO4, filtered and concentrated under reduced pressure to provide additional crude material. The aqueous layer was basified using 1 N NaOH to about pH 9. The precipitate was collected by vacuum filtration, combined with the batches collected from the organic layers and dried in a vacuum oven at about 50° C. for about 16 h to afford 1-methyl-3-(1,2,4-oxadiazol-3-yl)-1H-pyrazol-5-amine (1.2 g, 7.27 mmol, 71%, which was used without further purification). LC-MS (Table 1, Method g) Rt=0.71 min, m/z 166 (M+H)+. 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 9.55 (s, 1H), 5.80 (s, 1H), 5.47 (s, 2H), 3.61 (s, 3H).

1. customThe ice bath was removed after about 10 min
2. filtrationThe reaction mixture was filtered through a pad of Celite®
3. washrinsing with MeOH (30 mL)
4. concentrationconcentrated under reduced pressure
5. customThe crude material was partitioned between DCM (20 mL) and water (10 mL)
6. customThe organic layer was separated
7. extractionthe aqueous layer was back extracted with DCM (20 mL)
8. dry with materialThe combined organic layers were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. additionwas added
12. customThe organic layer was separated
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customto provide additional crude material
17. filtrationThe precipitate was collected by vacuum filtration
18. customcollected from the organic layers
19. customdried in a vacuum oven at about 50° C. for about 16 h