Ethyl Acetate → Ethyl 5-((5-fluoropyridin-3-yl)amino)-3-(methylthio)-1,2,4-triazine-6-carboxylate

HRID 577424Notes

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

Participants

Conditions

Temperature: 100 °C

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 3-amino-5-fluoropyridine (728 mg, 6.50 mmol) and then DIEA (0.45 mL, 2.60 mmol). The mixture was stirred at 100° C. for 1.5 h. To the mixture were poured 200 mL EtOAc. The mixture was washed with brine twice and water twice, dried in MgSO4, and concentrated in vacuo to afford crude ethyl 5-((5-fluoropyridin-3-yl)amino)-3-(methylthio)-1,2,4-triazine-6-carboxylate. It was stirred in 30 mL “7.0 N ammonia in methanol” (Acros, #133710010) as a slurry for overnight. The solid was isolated by filtration, washed with hexane and dried in vacuum oven. It was very pure 5-((5-fluoropyridin-3-yl)amino)-3-(methylthio)-1,2,4-triazine-6-carboxamide. Yield was 189 mg (52% for 2 steps).

Workup

washThe mixture was washed with brine twice
dry with materialwater twice, dried in MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-08d6695a8b7e48fb83509069f9e2ed10
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040530B2

Reaction notes

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