Methyl iodide → 1-(2,6-Dichloro-pyridine-4-carbonyl)-2-methyl-3-(2,3,4-trifluoro-phenyl)isothiourea

HRID 2092222Notes

Reaction equation

HRID 2092222 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([C:10]([NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[C:17]=2[F:24])=[S:14])=[O:11])[CH:7]=[C:6]([Cl:25])[N:5]=1.[CH3:26]I>C1COCC1>[Cl:3][C:4]1[CH:9]=[C:8]([C:10]([NH:12][C:13](=[N:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[C:17]=2[F:24])[S:14][CH3:26])=[O:11])[CH:7]=[C:6]([Cl:25])[N:5]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59455898HCID 59455898, compound

Product 1

HCID 1361160171-(2,6-Dichloro-pyridine-4-carbonyl)-2-methyl-3-(2,3,4-trifluoro-phenyl)isothiourea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (2.70 g, 0.06747 mol) was added carefully to a cooled solution (0° C.) of intermediate D9 (28.5 g, 0.04498 mol) in THF (200 ml). The mixture was stirred for 15 minutes and then CH3I (6.38 g, 0.04498 mol) was added. The ice-bath was removed and the reaction mixture was stirred for 2 hours at room temperature. Subsequently, the mixture was quenched with H2O and extracted with CH2Cl2 (3×100 ml). The combined organic layers were washed (brine), dried (MgSO4), filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (eluent: heptane/EtOAc gradiënt from 80/20 to 50/50). The desired fractions were collected and the solvent was evaporated. Yield: 5.7 g of intermediate D10 (32%).

Workup

  1. customThe ice-bath was removed
  2. stirringthe reaction mixture was stirred for 2 hours at room temperature
  3. customSubsequently, the mixture was quenched with H2O
  4. extractionextracted with CH2Cl2 (3×100 ml)
  5. washThe combined organic layers were washed (brine)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated in vacuo
  9. customThe residue was purified by flash chromatography (eluent: heptane/EtOAc gradiënt from 80/20 to 50/50)
  10. customThe desired fractions were collected
  11. customthe solvent was evaporated

Sources & evidence

ORD record
ord-4371630d45f0467d85ceaf5aaafdc9d4
Source dataset
uspto-grants-2013_05
Patent number
US08440701B2

Reaction notes

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