N,N-Dimethylaniline → Methyl 2-(4-chloro-6-phenyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

HRID 1399732Notes

Reaction equation

HRID 1399732 reaction equation
O=[C:2]1[NH:7][C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:5][C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:3]1[CH:20]([CH2:25][CH2:26][CH3:27])[C:21]([O:23][CH3:24])=[O:22].P(Cl)(Cl)([Cl:30])=O.CN(C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:30][C:2]1[C:3]([CH:20]([CH2:25][CH2:26][CH3:27])[C:21]([O:23][CH3:24])=[O:22])=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[N:7]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 136346149Methyl 2-(6-oxo-4-phenyl-2-(piperidin-1-yl)-1,6-dihydropyrimidin-5-yl)pentanoate

Product 1

HCID 86665655Methyl 2-(4-chloro-6-phenyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of methyl 2-(6-oxo-4-phenyl-2-(piperidin-1-yl)-1,6-dihydropyrimidin-5-yl)pentanoate (1.74 g; 4,71 mmol) in dry toluene (10 mL) under nitrogen atmosphere were carefully added phosphorus oxychloride (4.38 mL; 47.1 mmol) and dimethylaniline (0.476 mL; 3.77 mmol) and the reaction mixture was heated to reflux for 3 h. The volatiles were removed under reduced pressure (while the reaction mixture was still at elevated temperature), the residue was cooled in an ice-bath and quenched by adding crushed ice and a saturated solution of sodium hydrogen carbonate until neutralization. The aqueous layer was extracted with ethyl acetate, the organics were collected, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane furnished 0.040 g (1.6%, over 3 last steps) of the title compound as a yellow oil.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 3 h
  3. customThe volatiles were removed under reduced pressure (while the reaction mixture
  4. temperaturewas cooled in an ice-bath
  5. customquenched
  6. additionby adding
  7. customcrushed ice
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. customthe organics were collected
  10. dry with materialdried over magnesium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane

Sources & evidence

ORD record
ord-4db140e7f1c84507b9ef8e4296dad37c
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

Loading…