Potassium Carbonate → 6-cyclopropyl-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2-phenylethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 1889471Notes

Reaction equation

HRID 1889471 reaction equation
[CH:1]1([C:4]2[S:22][C:7]3[NH:8][C:9](=[O:21])[N:10]([CH2:13][CH2:14]N4CCOCC4)[C:11](=[O:12])[C:6]=3[CH:5]=2)[CH2:3][CH2:2]1.Br[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[C:37]2[N:41]=C(C(Cl)(Cl)Cl)O[N:38]=2)=[CH:27][CH:26]=1.[C:46](=[O:49])([O-])[O-:47].[K+].[K+]>C(#N)C>[CH:1]1([C:4]2[S:22][C:7]3[N:8]([CH2:24][C:25]4[CH:26]=[CH:27][C:28]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=5[C:37]5[NH:38][C:46](=[O:49])[O:47][N:41]=5)=[CH:29][CH:30]=4)[C:9](=[O:21])[N:10]([CH2:13][CH2:14][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:11](=[O:12])[C:6]=3[CH:5]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 15290996HCID 15290996, compoundHCID 593518146-cyclopropyl-3-(2-morpholin-4-ylethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1360522896-cyclopropyl-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2-phenylethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 135.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-cyclopropyl-3-(2-morpholin-4-ylethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.50 g), 3-[4′-(bromomethyl)biphenyl-2-yl]-5-(trichloromethyl)-1,2,4-oxadiazole (0.86 g), potassium carbonate (0.44 g) and acetonitrile (20 mL) was stirred at room temperature for 2 hr. Insoluble material was filtered off, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography and dissolved in tetrahydrofuran (4 ml) and methanol (4 mL). 1N Aqueous sodium hydroxide solution (4 mL) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was adjusted to pH 4 with water and 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 residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.76 g, 84%).

Workup

  1. filtrationInsoluble material was filtered off
  2. concentrationthe filtrate was concentrated
  3. customThe obtained residue was purified by silica gel column chromatography
  4. dissolutiondissolved in tetrahydrofuran (4 ml)
  5. addition1N Aqueous sodium hydroxide solution (4 mL) was added
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe obtained ethyl acetate layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e826bf4e00b74481ab5e65868738bcc6
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

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