Dimethylformamide → HCID 136052380, compound

HRID 1889511Notes

Reaction equation

HRID 1889511 reaction equation
[CH2:1]([C:3]1[S:38][C:6]2[N:7]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:26]4[N:30](COCCOC)[C:29](=[O:37])[O:28][N:27]=4)=[CH:16][CH:15]=3)[C:8](=[O:12])[NH:9][C:10](=[O:11])[C:5]=2[CH:4]=1)[CH3:2].Br[CH2:40][C:41]([C:43]1[CH:52]=[CH:51][CH:50]=[CH:49][C:44]=1[C:45]([O:47]C)=[O:46])=[O:42].CN(C)C=O.[H-].[Na+]>C(OCC)(=O)C>[CH2:1]([C:3]1[S:38][C:6]2[N:7]([CH2:13][C:14]3[CH:15]=[CH:16][C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:26]4[NH:30][C:29](=[O:37])[O:28][N:27]=4)=[CH:18][CH:19]=3)[C:8](=[O:12])[N:9]([CH2:40][C:41]([C:43]3[CH:52]=[CH:51][CH:50]=[CH:49][C:44]=3[C:45]([OH:47])=[O:46])=[O:42])[C:10](=[O:11])[C:5]=2[CH:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 244032methyl 2-(2-bromoacetyl)benzoateHCID 59351634HCID 59351634, compound

Product 1

HCID 136052380HCID 136052380, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 6-ethyl-1-[(2′-{4-[(2-methoxyethoxy)methyl]-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl}biphenyl-4-yl)methyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (2 g), methyl 2-(bromoacetyl)benzoate (1.06 g) and N,N-dimethylformamide (50 mL) was added sodium hydride (0.18 g), and the mixture was stirred at room temperature for 16 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. The residue was purified by silica gel column chromatography, tetrahydrofuran (15 mL), methanol (15 mL) and 1N aqueous sodium hydroxide solution (10 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, adjusted to pH 4 with 1N hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL), N,N′-carbonyldiimidazole (0.2 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.17 mL) were added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to give the title compound as a colorless amorphous solid (0.18 g, 30%).

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. customThe residue was purified by silica gel column chromatography, tetrahydrofuran (15 mL), methanol (15 mL) and 1N aqueous sodium hydroxide solution (10 mL)
  5. additionwere added
  6. stirringthe mixture was stirred at room temperature for 2 hr
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. extractionextracted with ethyl acetate
  9. washThe ethyl acetate layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. dissolutionThe residue was dissolved in tetrahydrofuran (100 mL)
  13. additionN,N′-carbonyldiimidazole (0.2 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.17 mL) were added
  14. stirringthe mixture was stirred at room temperature for 1 hr
  15. additionThe reaction mixture was diluted with ethyl acetate
  16. washwashed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. customThe obtained residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-b8e8d7db5def4f839001b4718be2a6bf
Source dataset
uspto-grants-2013_08
Patent number
US08501750B2

Reaction notes

Loading…