Sodium hydride → HCID 68194364, compound

HRID 2370612Notes

Reaction equation

HRID 2370612 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:9]([C:10]([O:12]CC)=O)=[CH:8][N:7]=[C:6]([S:15][CH3:16])[N:5]=1.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]=[C:25]=[O:26]>CN(C)C=O.[Cl-].[Na+].O.O>[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[C:10](=[O:12])[C:9]2[C:4](=[N:5][C:6]([S:15][CH3:16])=[N:7][CH:8]=2)[NH:3][C:25]1=[O:26]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 76833Chlorophenyl isocyanateHCID 2226665-Pyrimidinecarboxylic acid, 4-amino-2-(methylthio)-, ethyl ester

Product 1

HCID 68194364HCID 68194364, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

NaH (5.26 g, 131 mmol) was added to a solution of ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate (20.0 g, 94 mmol, US 2005/0020590) in N,N-dimethylformamide (700 mL) at 0° C. After 10 minutes, 1-chloro-2-isocyanatobenzene (15.9 mL, 131 mmol) was added dropwise to the mixture. The reaction was warmed to room temperature and stirred for 6 hours. The reaction mixture was diluted with brine (200 mL) and water (1000 mL) and extracted with ether (700 mL 2×). The aqueous layer was acidified with 5% citric acid (until pH=4-5), treated with brine, and extracted with ethyl acetate (2×). The combined organic layers were washed with water (2×), dried over MgSO4, filtered, and concentrated to remove most of the solvent. The mixture was filtered, and the solid was washed with cold ethyl acetate, and oven dried to provide the title compound.

Workup

  1. extractionextracted with ether (700 mL 2×)
  2. additiontreated with brine
  3. extractionextracted with ethyl acetate (2×)
  4. washThe combined organic layers were washed with water (2×)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto remove most of the solvent
  9. filtrationThe mixture was filtered
  10. washthe solid was washed with cold ethyl acetate, and oven
  11. customdried

Sources & evidence

ORD record
ord-45f257b61807409e87eca5e6465ece76
Source dataset
uspto-grants-2014_04
Patent number
US08710065B2

Reaction notes

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