Sulfuric Acid → HCID 67196854, compound

HRID 550803Notes

Reaction equation

HRID 550803 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[N:10]=[C:11]([N:20]3[CH2:26][CH2:25][C:24](=[O:27])[NH:23][CH2:22][CH2:21]3)[C:12]3[CH2:17][S:16](=[O:19])(=[O:18])[CH2:15][C:13]=3[N:14]=2)=[C:4]([F:28])[CH:3]=1.S(=O)(=O)(O)[OH:30]>>[ClH:1].[ClH:1].[NH2:23][CH2:22][CH2:21][N:20]([C:11]1[C:12]2[CH2:17][S:16](=[O:19])(=[O:18])[CH2:15][C:13]=2[N:14]=[C:9]([C:5]2[CH:6]=[C:7]([F:8])[C:2]([Cl:1])=[CH:3][C:4]=2[F:28])[N:10]=1)[CH2:26][CH2:25][C:24]([OH:27])=[O:30]

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 67195634HCID 67195634, compound

Product 1

HCID 67196854HCID 67196854, compound

Conditions

Temperature
100 °C

Procedure

A mixture of 321 mg of 1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxido-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl]-1,4-diazepan-5-one and 10 ml of 5% sulfuric acid was stirred at 100° C. for 27 hours. After the solvent was distilled off under reduced pressure, 10 ml of dioxane, 10 ml of saturated aqueous sodium bicarbonate solution, and 0.18 g of DIBOC (tert-butoxycarbonyl anhydride) were added in turn to the residue obtained, and the mixture was stirred at ambient temperature for 1 hour. Precipitate was filtered, and the filtrate was evaporated under reduced pressure. The residue was dissolved in chloroform, washed with 5% aqueous citric acid solution and then water, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and 4M HCl-dioxane solution was added to the residue, the resultant solution was stirred, and then the solvent was distilled off under reduced pressure. To the residue was added saturated aqueous sodium bicarbonate solution, the aqueous solution was washed with chloroform, added 5% aqueous citric acid, and extracted with chloroform. The organic extract was washed with water, and the solvent was distilled off under reduced pressure. The residue was dissolved in THF, here was added 4M HCl-dioxane solution, precipitate was collected by filtration to yield 92 mg of N-(2-aminoethyl)-N-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxido-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl]-β-alanine dihydrochloride as colorless solid.

Workup

  1. distillationAfter the solvent was distilled off under reduced pressure, 10 ml of dioxane, 10 ml of saturated aqueous sodium bicarbonate solution, and 0.18 g of DIBOC (tert-butoxycarbonyl anhydride)
  2. additionwere added in turn to the residue
  3. customobtained
  4. stirringthe mixture was stirred at ambient temperature for 1 hour
  5. filtrationPrecipitate was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. dissolutionThe residue was dissolved in chloroform
  8. washwashed with 5% aqueous citric acid solution
  9. dry with materialwater, and dried over anhydrous magnesium sulfate
  10. distillationThe solvent was distilled off under reduced pressure, and 4M HCl-dioxane solution
  11. additionwas added to the residue
  12. stirringthe resultant solution was stirred
  13. distillationthe solvent was distilled off under reduced pressure
  14. additionTo the residue was added saturated aqueous sodium bicarbonate solution
  15. washthe aqueous solution was washed with chloroform
  16. additionadded 5% aqueous citric acid
  17. extractionextracted with chloroform
  18. extractionThe organic extract
  19. washwas washed with water
  20. distillationthe solvent was distilled off under reduced pressure
  21. dissolutionThe residue was dissolved in THF
  22. additionhere was added 4M HCl-dioxane solution, precipitate
  23. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-70fc2f229b64417db8c810ed22eef537
Source dataset
uspto-grants-2011_05
Patent number
US07947690B2

Reaction notes

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