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

HRID 1837464Notes

Reaction equation

HRID 1837464 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[C:5]([C:15]([O:17][CH3:18])=[O:16])=[C:4]([CH:19]([CH3:21])[CH3:20])[N:3]=1.CCC([O-])(C)C.[Na+].[CH3:29][S:30](Cl)(=[O:32])=[O:31].S(OC)(O[CH3:38])(=O)=O.[Cl-].[Na+]>C(COC)OC.O>[F:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[C:5]([C:15]([O:17][CH3:18])=[O:16])=[C:4]([CH:19]([CH3:21])[CH3:20])[N:3]=[C:2]([N:1]([CH3:38])[S:30]([CH3:29])(=[O:32])=[O:31])[N:7]=2)=[CH:13][CH:12]=1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 6497Dimethyl SulfateHCID 31297Methanesulfonyl chlorideHCID 2733478Sodium 2-methylbutan-2-olate2×HCID 10424248Methyl 2-amino-4-(4-fluorophenyl)-6-isopropylpyrimidine-5-carboxylate

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A mixture of methyl 2-amino-4-(4-fluorophenyl)-6-isopropyl-pyrimidine-5-carboxylate (19.0 g), sodium tert-pentoxide (22.95 g) and dimethoxyethane (190 ml) was stirred for 30 minutes at 25° C. The stirred mixture was cooled to −10° C. and methanesulfonyl chloride (8.4 ml) was added dropwise, maintaining the temperature of the mixture at −5° C. After 20 minutes, dimethyl sulfate (8.1 ml) was added and the mixture allowed to warm to 25° C. The mixture was stirred for one hour at 25° C. and a solution of sodium tert-pentoxide (1.91 g) in dimethoxyethane (10 ml) added. The mixture was stirred for one hour at 25° C. A solution of sodium chloride (13.3 g) in water (133 ml) was added and the mixture was stirred for 10 minutes at 25° C. The mixture was allowed to settle for 15 minutes and the lower aqueous phase was separated and discarded. Water (38 ml) was added to the remaining mixture and the mixture was stirred for 30 minutes at 25° C. The mixture was then heated to obtain a complete solution. The mixture was cooled slowly to 25° C. over one hour. The mixture was cooled to 0° C., stirred for one hour, and the suspended solid collected by filtration. The solid was washed with cold (0° C.) solution of 50:50 water/dimethoxyethane (20 ml). The solid was dried under vacuum at 60° C. to give methyl 4-(4-fluorophenyl)-6isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidine-5-carboxylate (19.35 g); 1HNMR (270 MHz, CDCl3): 7.69 (m,2H), 7.14 (m,2H), 3.71, 3.60, 3.51(3× s, 9H), 3.20 (m, 1.(d,6H).

Workup

  1. temperatureThe stirred mixture was cooled to −10° C.
  2. temperaturemaintaining the temperature of the mixture at −5° C
  3. waitAfter 20 minutes
  4. temperatureto warm to 25° C
  5. stirringThe mixture was stirred for one hour at 25° C.
  6. stirringThe mixture was stirred for one hour at 25° C
  7. stirringthe mixture was stirred for 10 minutes at 25° C
  8. waitto settle for 15 minutes
  9. customthe lower aqueous phase was separated
  10. additionWater (38 ml) was added to the remaining mixture
  11. stirringthe mixture was stirred for 30 minutes at 25° C
  12. temperatureThe mixture was then heated
  13. customto obtain a complete solution
  14. temperatureThe mixture was cooled slowly to 25° C. over one hour
  15. temperatureThe mixture was cooled to 0° C.
  16. stirringstirred for one hour
  17. filtrationthe suspended solid collected by filtration
  18. washThe solid was washed with cold (0° C.) solution of 50:50 water/dimethoxyethane (20 ml)
  19. customThe solid was dried under vacuum at 60° C.

Sources & evidence

ORD record
ord-94884253630442e3b37eac84d2661c8e
Source dataset
uspto-grants-2004_08
Patent number
US06784171B2

Reaction notes

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