Methyl iodide → HCID 57785965, compound

HRID 1399162Notes

Reaction equation

HRID 1399162 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]3=[N:14][C:15]4[C:16](=[C:17]([C:22]([O:24][CH3:25])=[O:23])[CH:18]=[CH:19][C:20]=4[Cl:21])[N:12]3[CH2:11][CH2:10][CH2:9]2)=[C:4]([Cl:26])[CH:3]=1.C[O-].[Na+].[C:30](=O)([O-])[O-:31].[K+].[K+].CI>CN(C)C=O.[Cu]I>[Cl:21][C:20]1[CH:19]=[CH:18][C:17]([C:22]([O:24][CH3:25])=[O:23])=[C:16]2[C:15]=1[N:14]=[C:13]1[N:8]([C:5]3[CH:6]=[CH:7][C:2]([O:31][CH3:30])=[CH:3][C:4]=3[Cl:26])[CH2:9][CH2:10][CH2:11][N:12]21

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 10942334Sodium MethoxideHCID 57786131HCID 57786131, compound

Product 1

HCID 57785965HCID 57785965, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 1-(4-bromo-2-chlorophenyl)-9-chloro-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (200.0 mg, 0.439 mmol) in N,N-dimethylformamide (2.0 mL) were added copper(I) iodide (125.5 mg, 0.659 mmol) and sodium methoxide (28% wt methanol solution, 1.0 mL). The reaction mixture was stirred at 100° C. for 10 hrs. After cooling, the mixture was filtered through on the pad of celite. The filtrate was diluted with water and extracted with ethyl acetate (×1). The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate (×3). The combined organic layer was washed with brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude product was subject to next step without further purification. The resulting carboxylic acid was dissolved into N,N-dimethylformamide (3.0 mL) and to the mixture were added potassium carbonate (130.9 mg, 0.947 mmol) and methyl iodide (88.5 μL, 1.422 mmol) at 0° C. The reaction mixture was stirred at room temperature for 16.5 hrs. The mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-35% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless amorphous (121.8 mg, 0.300 mmol, 68% (2 steps)).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered through on the pad of celite
  3. additionThe filtrate was diluted with water
  4. extractionextracted with ethyl acetate (×1)
  5. extractionextracted with ethyl acetate (×3)
  6. washThe combined organic layer was washed with brine (×1)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was subject to next step without further purification
  11. dissolutionThe resulting carboxylic acid was dissolved into N,N-dimethylformamide (3.0 mL) and to the mixture
  12. stirringThe reaction mixture was stirred at room temperature for 16.5 hrs
  13. customThe mixture was quenched with aqueous saturated ammonium chloride
  14. extractionextracted with ethyl acetate (×3)
  15. washThe combined organic layer was washed with water (×2) and brine (×1)
  16. dry with materialdried over anhydrous magnesium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo
  19. customThe residue was purified by silica gel column chromatography
  20. washeluting with a 0-35% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-7ddc9016b1ec4b478fa5d14c0c22472e
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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