Sodium hydride → 7-(4-methyl-1H-imidazol-1-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

HRID 1853001Notes

Reaction equation

HRID 1853001 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.[H-].[Na+].Cl[C:10]1[N:15]=[C:14]([C:16]2[CH:17]=[N:18][N:19]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:20]=2)[N:13]2[CH:29]=[CH:30][N:31]=[C:12]2[CH:11]=1>CN(C)C=O>[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:10]2[N:15]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[CH:20]=3)[N:13]3[CH:29]=[CH:30][N:31]=[C:12]3[CH:11]=2)[CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 866852957-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidineHCID 178418800HCID 178418800, compound

Product 1

HCID 674586787-(4-methyl-1H-imidazol-1-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidineYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask charged with 4-methyl-1H-imidazole (0.117 g, 1.43 mmol) and 1 mL of N,N-dimethylformamide was added sodium hydride (60% in oil dispersion) (0.0514 g, 1.29 mmol) at 0° C. with stirring. The reaction mixture was then placed under nitrogen and allowed to warm to ambient temperature and stirred for 30 minutes. To the reaction was added 7-chloro-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (Preparation G; 0.100 g, 0.286 mmol) and argon was bubbled through the reaction for 5 minutes. The reaction was sealed and heated to 100° C. The reaction was diluted with dichloromethane (50 mL) and 5 mL of aqueous saturated sodium bicarbonate was added. The reaction mixture was stirred for 20 minutes, then concentrated to dryness under reduced pressure at 50° C. and dried on high vacuum overnight. The crude material was taken up in 1:1 ethyl acetate: dichloromethane with 5% methanol (100 mL) and sonicated for 1 hour. This suspension was filtered, the cake was washed with EtOAc (50 mL) and the rinse was then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography eluting with 1% methanol in dichloromethane containing 0.5% ammonium hydroxide to obtain 7-(4-methyl-1H-imidazol-1-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.053 g, 0.077 mmol, 27% yield). MS (apci) m/z=396.2 (M+H).

Workup

  1. stirringstirred for 30 minutes
  2. customwas bubbled through the reaction for 5 minutes
  3. customThe reaction was sealed
  4. temperatureheated to 100° C
  5. additionThe reaction was diluted with dichloromethane (50 mL) and 5 mL of aqueous saturated sodium bicarbonate
  6. additionwas added
  7. stirringThe reaction mixture was stirred for 20 minutes
  8. concentrationconcentrated to dryness under reduced pressure at 50° C.
  9. customdried on high vacuum overnight
  10. customdichloromethane with 5% methanol (100 mL) and sonicated for 1 hour
  11. filtrationThis suspension was filtered
  12. washthe cake was washed with EtOAc (50 mL)
  13. concentrationthe rinse was then concentrated under reduced pressure
  14. customThe resulting residue was purified by silica gel chromatography
  15. washeluting with 1% methanol in dichloromethane containing 0.5% ammonium hydroxide

Sources & evidence

ORD record
ord-857feff8426f4f0b9bdd983a602f9a19
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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