Potassium Carbonate → 5-(2-Chloro-pyridin-3-yl)-1-(3,3-dimethoxy-propyl)-1H-pyrimidine-2,4-dione

HRID 12720Notes

Reaction equation

HRID 12720 reaction equation
Cl.[Cl:2][C:3]1[C:8]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[O:15])[NH:13][CH:14]=2)=[CH:7][CH:6]=[CH:5][N:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][CH2:25][CH:26]([O:29][CH3:30])[O:27][CH3:28]>CN(C=O)C>[Cl:2][C:3]1[C:8]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[O:15])[N:13]([CH2:24][CH2:25][CH:26]([O:29][CH3:30])[O:27][CH3:28])[CH:14]=2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1189323-Bromopropionaldehyde dimethylacetalHCID 866159495-(2-Chloro-pyridin-3-yl)-1H-pyrimidine-2,4-dione hydrochloride

Product 1

HCID 589942035-(2-Chloro-pyridin-3-yl)-1-(3,3-dimethoxy-propyl)-1H-pyrimidine-2,4-dioneYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 5-(2-chloro-pyridin-3-yl)-1H-pyrimidine-2,4-dione hydrochloride salt (Prep95, 803 mg, 3.10 mmol) and K2CO3 (428 mg, 3.10 mmol) in DMF (15 ml), 90% 3-bromo-1,1dimethoxy-propane (516 μl, 3.41 mmol) was added in three portions over 5 days. The mixture was contemporarily stirred at room temperature. Solvent was then removed in vacuum at 40° C. The residue washed with petroleum ether and then with ethyl acetate. Ethyl acetate phase was dried (Na2SO4), filtered and evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98:2:0.2) to give 400 mg of the final compound as a white solid (40% yield)

Workup

  1. additionwas added in three portions over 5 days
  2. customSolvent was then removed in vacuum at 40° C
  3. washThe residue washed with petroleum ether
  4. dry with materialEthyl acetate phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude was purified by flash chromatography
  8. washeluting with DCM-MeOH—NH4OH (98:2:0.2)

Sources & evidence

ORD record
ord-ddd01cb341e9463f97cacdc3053be46d
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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