4-Fluoroaniline → N-(4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

HRID 1631614Notes

Reaction equation

HRID 1631614 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.C[Al](C)C.[CH3:13][N:14]1[C:19](=[O:20])[CH:18]=[C:17]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:16]=[C:15]1[CH2:27][C:28](OCC)=[O:29].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:28](=[O:29])[CH2:27][C:15]2[N:14]([CH3:13])[C:19](=[O:20])[CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:16]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 97314-FluoroanilineHCID 62657Potassium Phosphate, TribasicHCID 16682925TrimethylaluminumHCID 57523683Ethyl [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate

Product 1

HCID 66883557N-(4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

0.135 ml of 4-fluoroaniline and 0.670 ml of a 2M solution of trimethylaluminium are added, dropwise, to a solution of 190 mg of ethyl [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 10 ml of toluene. After stirring for 30 minutes at ambient temperature, 10 ml of toluene are added. After stirring for 4 hours at ambient temperature, the reaction mixture is poured into water and a 1M solution of potassium phosphate is added. The precipitate is filtered through sintered glass and then rinsed with ethyl acetate. The filtrate is then washed with water and then with a saturated aqueous solution of sodium chloride. The organic phase is extracted and then dried over magnesium sulphate, filtered through sintered glass, and concentrated under reduced pressure. After purification of the residue by silica column chromatography, elution being carried out with a mixture of dichloromethane and methanol (95/05, V/V), 20 mg of N-(4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following:

Workup

  1. stirringAfter stirring for 4 hours at ambient temperature
  2. filtrationThe precipitate is filtered through sintered glass
  3. washrinsed with ethyl acetate
  4. washThe filtrate is then washed with water
  5. extractionThe organic phase is extracted
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered through sintered glass
  8. concentrationconcentrated under reduced pressure
  9. customAfter purification of the residue
  10. washby silica column chromatography, elution
  11. additionbeing carried out with a mixture of dichloromethane and methanol (95/05, V/V), 20 mg of N-(4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide
  12. customare obtained in the form of a white solid

Sources & evidence

ORD record
ord-5080050ffea7405d9ca9b47fe3aa5515
Source dataset
uspto-grants-2014_07
Patent number
US08791255B2

Reaction notes

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