Reaction #5424

Reaction equation

diethyl 2-methylpyrimidine-4,5-dicarboxylate

2-amino-2,3-dimethylbutyramide

→

2-methyl-4-(4-methyl-4-isopropylimidazolin-5-on-2-yl)-pyrimidine-5carboxylic acid

Yield 51.5%

Solvents

toluene

Conditions

Workup

1. 1
   Temperaturethe reaction mixture is cooled
2. 2
   Otherthe solid which has precipitated
3. 3
   Filtrationis filtered
4. 4
   Washwashed several times with diethyl ether
5. 5
   workup.DISSOLUTIONsubsequently dissolved in water
6. 6
   Extractionthe mixture is extracted five times
7. 7
   DryingThe combined organic extracts are dried over sodium sulphate
8. 8
   Concentrationconcentrated in vacuo
9. 9
   OtherThe residue can be purified by chromatography on silica gel

Procedure

To a mixture of 98.8 g (0.415 mole) of diethyl 2-methylpyrimidine-4,5-dicarboxylate (compare, for example, J. Heterocycl. Chem. 2, 202-204 [1965]) and 54.0 g (0.415 mole) of 2-amino-2,3-dimethylbutyramide in 700 ml of anhydrous toluene there are added in portions 102.2 g (0.913 mole) of potassium tert.-butylate, and the mixture is subsequently stirred for 16 hours at 80° C. For working-up, the reaction mixture is cooled, the solid which has precipitated is filtered, washed several times with diethyl ether and subsequently dissolved in water. The aqueous solution is brought to pH 5 using half-concentrated hydrochloric acid, and the mixture is extracted five times using 200 ml portions of dichloromethane. The combined organic extracts are dried over sodium sulphate and concentrated in vacuo. The residue can be purified by chromatography on silica gel. 59 g (51% of theory) of 2-methyl-4-(4-methyl-4-isopropylimidazolin-5-on-2-yl)-pyrimidine-5carboxylic acid of melting point 56°-57° C. are obtained.

Source