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

HRID 577421Notes

Reaction equation

HRID 577421 reaction equation
Cl[C:2]1[N:3]=[C:4]([S:13][CH3:14])[N:5]=[N:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1.CCN(C(C)C)C(C)C.CCOC(C)=O>CN(C=O)C>[CH3:14][S:13][C:4]1[N:5]=[N:6][C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[N:3]=1

Participants

6

Reactant 4

HCID 7813p-ToluidineHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 11557703Ethyl 5-Chloro-3-(Methylthio)-1,2,4-Triazine-6-Carboxylate

Product 1

HCID 13553781Ethyl 3-(methylthio)-5-(p-tolylamino)-1,2,4-triazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  1. washThe mixture was washed with brine twice
  2. dry with materialdried in MgSO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a4bb3927f43f4acf9d991415e6e0f50b
Source dataset
uspto-grants-2015_05
Patent number
US09040530B2

Reaction notes

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