Hydrochloric Acid → Ethyl 3-methyl-2,4-dioxo-1-propyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylate

HRID 131572Notes

Reaction equation

HRID 131572 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([SH:9])[N:4]([CH2:10][CH2:11][CH3:12])[C:3]1=[O:13].C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][C:22](=O)[C:23]([O:25][CH2:26][CH3:27])=[O:24].Cl>CN(C)C=O.ClCCl.[Ti](Cl)(Cl)(Cl)Cl.O>[CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][S:9][C:5]=2[N:4]([CH2:10][CH2:11][CH3:12])[C:3]1=[O:13]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 66144Ethyl bromopyruvateHCID 866227106-Mercapto-3-methyl-1-propyl-pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 17974732Ethyl 3-methyl-2,4-dioxo-1-propyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

The product of step b) (6.95 g) in dry dimethylformamide (100 ml) was added potassium carbonate (2.4 g) and stirred for 10 min. Ethyl bromopyruvate (5 ml) was added and was stirred under nitrogen at room temperature for 2 h. The reaction was poured into water (1 L), acidified (2M HCl) and extracted with ethyl acetate. The organic extracts were washed with brine (100 ml). Drying and evaporation afforded an oil. The oil was dissolved in dichloromethane (100 ml) and cooled in ice whilst stirring. Titanium tetrachloride (7.58 ml) was added and stirring continued under nitrogen for 2 h. The reaction was poured into water (1 L) and extracted with dichloromethane. The organics were dried and evaporated in vacuo. The residue was purified by chromatography (SiO2/ethyl acetate-dichloromethane 0-8%) to afford the subtitle compound as an orange oil, 4.64 g. δ 1HCDCl3 1.02 (3H, t), 1.83 (2H, sextet), 3.42 (3H, s), 3.95 (2H, t), 4.41 (2H, q), 7.30 (1H, s). MS (APCI) 297.1 (M++H)

Workup

  1. stirringwas stirred under nitrogen at room temperature for 2 h
  2. extractionextracted with ethyl acetate
  3. washThe organic extracts were washed with brine (100 ml)
  4. customDrying
  5. customevaporation
  6. customafforded an oil
  7. temperaturecooled in ice
  8. stirringwhilst stirring
  9. stirringstirring
  10. waitcontinued under nitrogen for 2 h
  11. extractionextracted with dichloromethane
  12. customThe organics were dried
  13. customevaporated in vacuo
  14. customThe residue was purified by chromatography (SiO2/ethyl acetate-dichloromethane 0-8%)

Sources & evidence

ORD record
ord-ee08f61483ce4b388c418c3d2681ec37
Source dataset
uspto-grants-2008_06
Patent number
US07384950B2

Reaction notes

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