Hydrochloric Acid → 1-[3,3-bis(methyloxy)propyl]-5-(4-isothiazolyl)-2,4(1H,3H)-pyrimidinedione

HRID 1925027Notes

Reaction equation

HRID 1925027 reaction equation
Cl.[S:2]1[CH:6]=[C:5]([C:7]2[C:8](=[O:14])[NH:9][C:10](=[O:13])[NH:11][CH:12]=2)[CH:4]=[N:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH2:23][CH:24]([O:27][CH3:28])[O:25][CH3:26].Cl>CN(C)C=O.O>[CH3:26][O:25][CH:24]([O:27][CH3:28])[CH2:23][CH2:22][N:11]1[CH:12]=[C:7]([C:5]2[CH:4]=[N:3][S:2][CH:6]=2)[C:8](=[O:14])[NH:9][C:10]1=[O:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 1189323-Bromopropionaldehyde dimethylacetalHCID 67519670HCID 67519670, compound

Product 1

HCID 594483771-[3,3-bis(methyloxy)propyl]-5-(4-isothiazolyl)-2,4(1H,3H)-pyrimidinedioneYield 13.44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-(4-isothiazolyl)-2,4(1H,3H)-pyrimidinedione hydrochloride (Prep23, 300 mg, 1.036 mmol) was dissolved in N,N-Dimethylformamide (DMF) (4 ml) to give a pale yellow suspension. K2CO3 (215 mg, 1.554 mmol) was added ant the reaction mixture was stirred at room temperature for 1 h. 3-bromo-1,1-bis(methyloxy)propane (0.173 ml, 1.140 mmol) was added. Mixture was stirred at room temperature for 3 days, then diluted with water, acidified with diluted HCl until pH ˜5, and extracted with EtOAc. The organic phase was washed with water (3 times), brine, dried over Na2SO4, filtered and the solvent evaporated. The obtained residue was purified by flash chromatography eluting with cyclohexane/EtOAc 1:1. Obtained 60 mg (13.44% yield) of a 9:1 mixture of the title compound and the corresponding bis alkylated derivative.

Workup

  1. customto give a pale yellow suspension
  2. stirringMixture was stirred at room temperature for 3 days
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed with water (3 times), brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent evaporated
  8. customThe obtained residue was purified by flash chromatography
  9. washeluting with cyclohexane/EtOAc 1:1
  10. customObtained

Sources & evidence

ORD record
ord-e6711f020bb345af8d423ef606e16fde
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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