Toluene → Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylate

HRID 50107Notes

Reaction equation

HRID 50107 reaction equation
[NH2:1][C:2](=[C:10]([C:15](=O)[CH:16]([CH3:18])[CH3:17])[C:11]([O:13][CH3:14])=[O:12])[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.C1(C)C=CC=CC=1.[C:27]([N:29]([CH3:34])[S:30]([CH3:33])(=[O:32])=[O:31])#[N:28]>[Ti](Cl)(Cl)(Cl)Cl.O>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:2]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:15]([CH:16]([CH3:18])[CH3:17])[N:28]=[C:27]([N:29]([S:30]([CH3:33])(=[O:32])=[O:31])[CH3:34])[N:1]=2)=[CH:4][CH:5]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 10219456N-cyano-N-methylmethanesulphonamideHCID 178500902HCID 178500902, compound

Product 1

HCID 9929821Methyl 4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinecarboxylateYield 80.3%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

10.0 g (37.7 mmol) of methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate were introduced into 50 ml of toluene, together with 10.17 g (75.4 mmol) of N-cyano-N-methylmethanesulphonamide and the mixture was treated at room temperature with 3.61 g (18.9 mmol) of titanium tetrachloride. The reaction progressed exothermically. The red-orange-coloured suspension was heated to 110° C. and stirred for 4.5 h. It was then cooled to room temperature and treated with 30 ml of water. The organic phase was separated off and the aqueous phase was extracted with ethyl acetate (30 ml). The combined organic phases were washed with 30 ml of water and dried over magnesium sulphate. After filtering and concentrating the solution in a water-jet vacuum and drying in vacuo, 11.54 g of crude product were obtained in the form of a tacky oil.

Workup

  1. temperatureIt was then cooled to room temperature
  2. customThe organic phase was separated off
  3. extractionthe aqueous phase was extracted with ethyl acetate (30 ml)
  4. washThe combined organic phases were washed with 30 ml of water
  5. dry with materialdried over magnesium sulphate
  6. filtrationAfter filtering
  7. concentrationconcentrating the solution in a water-jet vacuum
  8. customdrying in vacuo

Sources & evidence

ORD record
ord-0efebf0306204be49d7b2753b8d39b9e
Source dataset
uspto-grants-2004_03
Patent number
US06710178B2

Reaction notes

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