Methyl iodide → 1-(2-Chloro-6-methyl-pyridine-4-carbonyl)-3-(3-methoxy-5-trifluoromethyl-phenyl)-2-methyl-isothiourea

HRID 2092218Notes

Reaction equation

HRID 2092218 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]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([O:26][CH3:27])[CH:17]=2)=[S:14])=[O:11])[CH:7]=[C:6]([CH3:28])[N:5]=1.[CH3:29]I>C1COCC1>[Cl:3][C:4]1[CH:9]=[C:8]([C:10]([NH:12][C:13](=[N:15][C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[C:18]([O:26][CH3:27])[CH:17]=2)[S:14][CH3:29])=[O:11])[CH:7]=[C:6]([CH3:28])[N:5]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 594558931-(2-Chloro-6-methyl-pyridine-4-carbonyl)-3-(3-methoxy-5-trifluoromethyl-phenyl)-thiourea

Product 1

HCID 1361160191-(2-Chloro-6-methyl-pyridine-4-carbonyl)-3-(3-methoxy-5-trifluoromethyl-phenyl)-2-methyl-isothioureaYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(Reaction performed under N2 atmosphere) NaH (1.267 g, 0.05279 mol) was added portionwise to an ice-cooled solution of intermediate D5 (21.32 g, 0.05279 mol) in THF (480 ml) and the resulting mixture was stirred for 15 minutes at 0° C. Subsequently, a solution of CH3I (7.493 g, 0.05279 mol) in THF (40 ml) was added dropwise and the mixture was stirred for 2 hours at room temperature. Then the reaction mixture was quenched with H2O and extracted with CH2Cl2 (3×500 ml). The organic layers were separated, combined, washed with brine, dried (MgSO4), filtered and the solvent was evaporated in vacuo. The crude product was triturated with DIPE/heptane. The off-white solid was filtered off and dried to yield 16.203 g of intermediate D6 (73.5%). Heptane and H2O were added to the filtrate and this mixture was stirred overnight at room temperature. The off-white precipitate was filtered off and dried to yield more (1.957 g) of intermediate D6 (9%).

Workup

  1. stirringthe mixture was stirred for 2 hours at room temperature
  2. customThen the reaction mixture was quenched with H2O
  3. extractionextracted with CH2Cl2 (3×500 ml)
  4. customThe organic layers were separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated in vacuo
  9. customThe crude product was triturated with DIPE/heptane
  10. filtrationThe off-white solid was filtered off
  11. customdried

Sources & evidence

ORD record
ord-ce136f6928c54b8fa7c8c18644ecfcc0
Source dataset
uspto-grants-2013_05
Patent number
US08440701B2

Reaction notes

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