Sodium hydride → 1-(6-Chloropyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea

HRID 58141

Reaction equation

HRID 58141 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH3:9])[CH:3]=1.[H-].[Na+].[Cl:12][C:13]1[C:18]([N:19]=[C:20]=[O:21])=[C:17]([Cl:22])[C:16]([O:23][CH3:24])=[CH:15][C:14]=1[O:25][CH3:26].[CH3:27][Si:28]([CH2:31][CH2:32][O:33][CH2:34]Cl)([CH3:30])[CH3:29].[NH4+].[Cl-]>CN(C=O)C.O>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]([CH3:9])[C:20]([N:19]([C:18]2[C:13]([Cl:12])=[C:14]([O:25][CH3:26])[CH:15]=[C:16]([O:23][CH3:24])[C:17]=2[Cl:22])[CH2:34][O:33][CH2:32][CH2:31][Si:28]([CH3:30])([CH3:29])[CH3:27])=[O:21])[CH:3]=1

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 3094796-chloro-N-methylpyrimidin-4-amineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 860869932,6-Dichloro-3,5-dimethoxyphenyl isocyanate

Product 1

HCID 1317369691-(6-Chloropyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureaYield 28.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a solution of 6-chloro-N-methylpyrimidin-4-amine (Procedure 2A, step e; 460 g, 3.21 mmol) in DMF (15 mL) was added NaH (60%, 193 g, 4.81 mmol) at 0° C., and the mixture was stirred for 30 minutes at room temperature. A solution of 2,4-dichloro-3-isocyanato-1,5-dimethoxy-benzene (Procedure H, steps a-d; 1.03 g, 4.17 mmol) in DMF (5 mL) was added dropwise at room temperature. The resulting mixture was stirred for 0.5 hour. SEMCl (804 g, 4.81 mmol) in DMF (2 mL) was added. The reaction mixture was stirred at room temperature for 1 hour. Saturated aqueous NH4Cl was added to quench the reaction. The mixture was diluted with water and extracted with EtOAc. The combined extracts were washed with water and brine, dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated under vacuum to give crude product, which was purified by flash chromatography on silica to obtain the title compound (470 mg, yield: 28%). MS (ESI): 521 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred for 0.5 hour
  2. stirringThe reaction mixture was stirred at room temperature for 1 hour
  3. customto quench
  4. customthe reaction
  5. extractionextracted with EtOAc
  6. washThe combined extracts were washed with water and brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customThe filtrate was evaporated under vacuum
  10. customto give crude product, which
  11. customwas purified by flash chromatography on silica

Sources & evidence

ORD record
ord-9a6d8de3ae3a44d398f2b6c615bbf87f
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Linked notes

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