Sodium Carbonate → 2-Chloro-3-methyl-6-(pyrimidin-4-YL)pyrimidin-4-one

HRID 1671482Notes

Reaction equation

HRID 1671482 reaction equation
S[C:2]1[N:3]([CH3:15])[C:4](=[O:14])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][N:9]=2)[N:7]=1.P(Cl)(Cl)([Cl:18])=O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])O.[Na+].Cl[O-].[Na+]>O.ClCCl.ClCCCl.CN(C)C=O>[Cl:18][C:2]1[N:3]([CH3:15])[C:4](=[O:14])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][N:9]=2)[N:7]=1

Participants

10

Reactant 5

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 23665760Sodium HypochloriteHCID 1784816782-Mercapto-3-methyl-6-(pyrimidin-4-YL)-3H-pyrimidin-4-one

Product 1

HCID 179544602-Chloro-3-methyl-6-(pyrimidin-4-YL)pyrimidin-4-oneYield 24.7%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 2-mercapto-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (8.8 g, 40 mmol) in a mixed solvent of dimethylformamide (30 ml) and 1,2-dichloroethane (30 ml) was added to phosphorus oxychloride (11.2 ml, 120 mmol), and the mixture was stirred at 65° C. for 50 min. After the solution was poured into ice-cooled dichloromethane (300 ml), water was added and the mixture was stirred vigorously for 5 min. Aqueous sodium carbonate solution (25.4 g, 240 mmol, in water (100 ml)) was added and the pH was adjusted to 8 with saturated aqueous sodium hydrogencarbonate solution. Aqueous sodium hypochlorite solution (5% in water, 120 ml) was added. After filtration through celite, the organic layer was separated and the aqueous layer was extracted with dichloromethane twice. The organic layers were combined and washed with saturated aqueous sodium hydrogencarbonate solution and dried over sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (eluent; ethyl acetate/hexane=1/1) and wash with diethyl ether to give 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (2.2 g, 62%, 98.7% purity) as a pale-yellow solid.

Workup

  1. additionAfter the solution was poured into ice-
  2. additionwas added
  3. stirringthe mixture was stirred vigorously for 5 min
  4. filtrationAfter filtration through celite
  5. customthe organic layer was separated
  6. extractionthe aqueous layer was extracted with dichloromethane twice
  7. washwashed with saturated aqueous sodium hydrogencarbonate solution
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (eluent; ethyl acetate/hexane=1/1)
  11. washwash with diethyl ether

Sources & evidence

ORD record
ord-0c063a0754f64b3c9558edfa7f29e80e
Source dataset
uspto-grants-2011_08
Patent number
US07994315B2

Reaction notes

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