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

HRID 1099054Notes

Reaction equation

HRID 1099054 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-59d2cf9b20dd483c867cf813da1cff86
Source dataset
uspto-grants-2012_03
Patent number
US08143251B2

Reaction notes

Loading…