Methyl iodide → 6-(4-Bromo-3-fluorophenyl)-3-(methylthio)-1,2,4-triazine

HRID 2245954Notes

Reaction equation

HRID 2245954 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9](OCC)OCC)=[CH:4][C:3]=1[F:17].[NH2:18][NH:19][C:20]([NH2:22])=[S:21].[CH3:23]I>C(O)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:18]=[N:19][C:20]([S:21][CH3:23])=[N:22][CH:9]=2)=[CH:4][C:3]=1[F:17]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2723789ThiosemicarbazideHCID 575165221-(4-Bromo-3-fluorophenyl)-2,2-diethoxyethanone

Product 1

HCID 668131126-(4-Bromo-3-fluorophenyl)-3-(methylthio)-1,2,4-triazineYield 52.2%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 702EthanolSolvent

Procedure

A solution of 1-(4-bromo-3-fluorophenyl)-2,2-diethoxyethanone (2.24 g, 0.00734 mol), thiosemicarbazide (0.702 g, 0.00771 mol), and p-toluenesulfonic acid monohydrate (70 mg) in ethanol (50 mL) was heated at 90° C. for 2 h. LCMS showed that the starting material was consumed. After cooled to RT, to the mixture was added methyl iodide (2.3 mL, 0.037 mol). The mixture was stirred at RT for 2 h, and concentrated. To the residue was added acetic acid (15 mL). The mixture was heated at 60° C. for 4 h. The volatiles were evaporated under reduced pressure. The residue was treated with methanol. The formed precipitate was collected by filtration, and dried in-vacuo to afford the desired product (1.15 g, 51%) which was directly used in next step without further purification.

Workup

  1. customwas consumed
  2. concentrationconcentrated
  3. additionTo the residue was added acetic acid (15 mL)
  4. temperatureThe mixture was heated at 60° C. for 4 h
  5. customThe volatiles were evaporated under reduced pressure
  6. additionThe residue was treated with methanol
  7. filtrationThe formed precipitate was collected by filtration
  8. customdried in-vacuo

Sources & evidence

ORD record
ord-6074fcb1cef446689b857502b1e5c913
Source dataset
uspto-grants-2010_03
Patent number
US07683060B2

Reaction notes

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