Dimethylformamide → HCID 136052248, compound

HRID 1889442Notes

Reaction equation

HRID 1889442 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]1[C:16](=[O:17])[C:15]2[CH:18]=[C:19]([CH2:21][CH3:22])[S:20][C:14]=2[NH:13][C:12]1=[O:23])(C(C)(C)C)(C)C.Br[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:38]2[N:42]=[C:41](C(Cl)(Cl)Cl)[O:40][N:39]=2)=[CH:28][CH:27]=1.CN(C)C=[O:50].[H-].[Na+]>C(OCC)(=O)C>[CH2:21]([C:19]1[S:20][C:14]2[N:13]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[C:38]4[NH:42][C:41](=[O:50])[O:40][N:39]=4)=[CH:28][CH:27]=3)[C:12](=[O:23])[N:11]([CH2:10][CH2:9][OH:8])[C:16](=[O:17])[C:15]=2[CH:18]=1)[CH3:22]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 15290996HCID 15290996, compoundHCID 59351819HCID 59351819, compound

Product 1

HCID 136052248HCID 136052248, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 3-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-6-ethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.14 g), 3-[4′-(bromomethyl)biphenyl-2-yl]-5-(trichloromethyl)-1,2,4-oxadiazole (0.22 g) and N,N-dimethylformamide (10 mL) was added sodium hydride (0.02 g), and the mixture was stirred at 50° C. for 1 hr. The reaction mixture was diluted with ethyl acetate, washed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To the obtained residue was added 1N aqueous sodium hydroxide solution (50 mL), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was adjusted to pH 4 with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and dissolved in tetrahydrofuran (10 mL). Tetrabutylammonium fluoride (1.0M tetrahydrofuran solution, 0.6 mL) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.07 g, 37%).

Workup

  1. washwashed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. additionTo the obtained residue was added 1N aqueous sodium hydroxide solution (50 mL)
  5. stirringthe mixture was stirred at 60° C. for 1 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe obtained ethyl acetate layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography
  11. dissolutiondissolved in tetrahydrofuran (10 mL)
  12. additionTetrabutylammonium fluoride (1.0M tetrahydrofuran solution, 0.6 mL) was added
  13. stirringthe mixture was stirred at room temperature for 2 hr
  14. additionThe reaction mixture was diluted with ethyl acetate
  15. washwashed with saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. customThe solvent was evaporated under reduced pressure
  18. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-166ef2d758754333a0867126b5070853
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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