Acetic Acid → 1,3,6-Trimethyl-2,4(1H,3H)-pyrimidinedione

HRID 1912352Notes

Reaction equation

HRID 1912352 reaction equation
COS([O:6][CH3:7])(=O)=O.O[C:9]1[N:14]=[C:13]([OH:15])[CH:12]=[C:11]([CH3:16])[N:10]=1.[C:17](O)(=O)C>[OH-].[Na+]>[CH3:17][N:10]1[C:11]([CH3:16])=[CH:12][C:13](=[O:15])[N:14]([CH3:9])[C:7]1=[O:6]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6497Dimethyl SulfateHCID 178429421HCID 178429421, compound

Product 1

HCID 260751,3,6-Trimethyl-2,4(1H,3H)-pyrimidinedioneYield 43%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
40 °C

Procedure

(See, e.g., Azas et al., Farmaco. 58:1263-1270 (2003)). Dimethylsulfate (106 g, 80 ml, 844 mmol) was added dropwise to a solution of 2,4-dihydroxy-6-methylpyrimidine (30 g, 238 mmol) in 280 mL of 4 N NaOH at 40° C. After stirring for 4 h at 40° C., the reaction mixture was neutralized with careful addition of acetic acid and extracted 3 times with 100 mL of ethyl acetate. Combined organics were dried over MgSO4 and concentrated in vacuo to yield a white solid. Recrystallization from ethanol yielded 2 (15.8 g, 43%): mp 113-114° C.; 1H NMR (DMSO-d6): δ 5.58 (s, 1H), 3.26 (s, 3H), 3.09 (s, 3H,), 2.19 (s, 3H,); MS (ES+) (m/z): [M+1]+ calculated for C7H11N2O2, 155.17. found 155.93. This compound matched the analytical data as reported (see, e.g., Azas et al., Farmaco. 58:1263-1270 (2003)).

Workup

  1. extractionextracted 3 times with 100 mL of ethyl acetate
  2. dry with materialCombined organics were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customto yield a white solid
  5. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-f1c7d9f0df544a1e9971014dffea12da
Source dataset
uspto-grants-2013_12
Patent number
US08609661B2

Reaction notes

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