Water → 4-Anilino-6-chloro-2-(methylsulfanyl)pyrimidine-5-carbaldehyde

HRID 556527Notes

Reaction equation

HRID 556527 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Cl:10][C:11]1[C:16]([CH:17]=[O:18])=[C:15](Cl)[N:14]=[C:13]([S:20][CH3:21])[N:12]=1.O>CS(C)=O.CCOC(C)=O>[Cl:10][C:11]1[C:16]([CH:17]=[O:18])=[C:15]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:14]=[C:13]([S:20][CH3:21])[N:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6115AnilineHCID 24758Sodium hydrideHCID 46140044,6-Dichloro-2-(methylsulfanyl)pyrimidine-5-carbaldehyde

Product 1

HCID 596396644-Anilino-6-chloro-2-(methylsulfanyl)pyrimidine-5-carbaldehydeYield 76%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of aniline (550 microliter (hereinafter “μL” or “uL”), 6 millimoles (hereinafter “mmol”), 1.2 equivalents (hereinafter “eq”)) in dry DMSO (100 mL) was added NaH as a 60% suspension in mineral oil (240 milligrams (hereinafter “mg”), 6 mmol, 1.2 eq) and the reaction mixture was stirred for 1 hour (hereinafter “h”). To the red solution was then added 4,6-dichloro-2-methylsulfanyl-pyrimidine-5-carbaldehyde (1.11 grams (hereinafter “g”), 5 mmol) [Santilli, et al., J. Heterocycl. Chem. 1971, 8, 445-45] dissolved in anhydrous DMSO (20 milliliters (hereinafter “mL”)). The reaction mixture turned yellow and was stirred 2 h at 23°, H2O (250 mL) was added followed by EtOAc (500 mL) The layers were separated; the organic layer was washed with saturated (hereinafter sat'd) aq. NaCl, dried (MgSO4) and filtered. The organic layer was evaporated and the crude residue was dissolved in isopropanol (50 mL) and heated to 60°, H2O (50 mL) was added and the solution was cooled slowly to 23°. The product was isolated by filtration and dried in vacuo to afford 1.06 g (76% yield) of pure 4-chloro-2-methylsulfanyl-6-phenylamino-pyrimidine-5-carbaldehyde. 1H-NMR δ 2.59 (s, 3H), 7.21 (m, 1H), 7.44 (m, 2H), 7.68 (m, 2H), 10.37 (s, 1H), 11.38 (br s, 1H). LC MS (m/e)=280 (MH+).

Workup

  1. stirringwas stirred 2 h at 23°
  2. customwere separated
  3. washthe organic layer was washed with saturated (hereinafter sat'd) aq. NaCl
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customThe organic layer was evaporated
  7. dissolutionthe crude residue was dissolved in isopropanol (50 mL)
  8. temperatureheated to 60°
  9. additionH2O (50 mL) was added
  10. temperaturethe solution was cooled slowly to 23°
  11. customThe product was isolated by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-02c75cecd8974f2db3b2609c988bfd9d
Source dataset
uspto-grants-2011_11
Patent number
US08058282B2

Reaction notes

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