p-Toluidine → Ethyl 3-(methylthio)-5-(p-tolylamino)-1,2,4-triazine-6-carboxylate

Participants

Reaction Steps

Ethyl 5-chloro-3-(methylthio)-1,2,4-triazine-6-carboxylate (300 mg, 1.29 mmol) was dissolved in 10 mL dry DMF. To it was added p-toluidine (166 mg, 1.55 mmol) and then DIEA (0.45 mL, 2.58 mmol). The mixture was stirred at RT for 1 h. To the mixture were poured 200 mL EtOAc. The mixture was washed with brine twice, dried in MgSO4, and concentrated in vacuo to afford crude ethyl 3-(methylthio)-5-(p-tolylamino)-1,2,4-triazine-6-carboxylate. It was dissolved in 20 mL “7.0 N ammonia in methanol” (Acros, #133710010) and stirred for overnight. Solid slowly crashed out in the reaction flask and a slurry was yielded. The solid was isolated by filtration, washed with hexane and dried in vacuum oven. It was very pure 3-(methylthio)-5-(p-tolylamino)-1,2,4-triazine-6-carboxamide. Yield was 94 mg (26% for 2 steps).

Provenance & Evidence