Dimethylformamide → 2-{2-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenylamino}-6-methoxy-4-(methoxycarbonyl)methoxypyrimidine

HRID 1862330Notes

Reaction equation

HRID 1862330 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[C:6]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[N:12]([CH3:21])[C:11]2=[O:22])=[CH:5][C:3]=1[NH2:4].[CH3:23][O:24][C:25]1[N:30]=[C:29](S(C)(=O)=O)[N:28]=[C:27]([O:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH:26]=1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O>[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[C:6]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([C:17]([F:19])([F:18])[F:20])[N:12]([CH3:21])[C:11]2=[O:22])=[CH:5][C:3]=1[NH:4][C:29]1[N:28]=[C:27]([O:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH:26]=[C:25]([O:24][CH3:23])[N:30]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 186191946-Methoxy-4-(methoxycarbonyl)methoxy-2-methylsulfonylpyrimidineHCID 186192573-(5-amino-4-chloro-2-fluorophenyl)-1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 186192622-{2-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenylamino}-6-methoxy-4-(methoxycarbonyl)methoxypyrimidineYield 15.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 400 mg of 2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline, 360 mg of 6-methoxy-4-(methoxycarbonyl)methoxy-2-methylsulfonylpyrimidine and 2 ml of N,N-dimethylformamide, 196 mg of potassium carbonate was added, and the mixture was stirred for 5 hours at 80° C. The reaction solution was cooled to room temperature, then, this reaction solution was poured into water, and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 98 mg of 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenylamino}-6-methoxy-4-(methoxycarbonyl)methoxypyrimidine [present compound 1-67].

Workup

  1. additionwas added
  2. temperatureThe reaction solution was cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f897f0bf17d343188d6a66e0be62fbd0
Source dataset
uspto-grants-2003_03
Patent number
US06537948B1

Reaction notes

Loading…