Tetrahydrofuran → 1-methyl-3-(1,2,4-oxadiazol-3-yl)-1H-pyrazol-5-amine

Participants

Reaction Steps

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).

Provenance & Evidence