Reaction #1583829

Reaction equation

methyl N-[[2-chloro-5-[3-(dimethylamino)-1-oxo-2-propen-1-yl]phenyl]-methyl]carbamate

product

methyl N-[[2-chloro-5-[3-(dimethylamino)-1-oxo-2-propen-1-yl]phenyl]methyl]carbamate

4-methylbenzamidine hydrochloride

sodium hydride

ammonium chloride

→

title compound

methyl N-[[2-chloro-5-[2-(4-methylphenyl)-4-pyrimidinyl]phenyl]methyl]-carbamate

Solvents

methanol

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was heated
2. 2
   Temperatureat reflux overnight
3. 3
   Concentrationthe mixture was concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONThe resulting residue was dissolved in ethyl acetate
5. 5
   Washwashed with saturated aqueous sodium carbonate
6. 6
   Dryingdried over magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherThe resulting residue was purified by medium pressure liquid chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

Procedure

To mixture of methyl N-[[2-chloro-5-[3-(dimethylamino)-1-oxo-2-propen-1-yl]phenyl]-methyl]carbamate (i.e. the product of Step A, Example 4) (0.43 g, 1.44 mmol), 4-methylbenzamidine hydrochloride (0.74 g, 4.33 mmol) and sodium hydride (0.14 g, 5.8 mmol) at 0° C. was slowly added methanol (5 mL). The reaction mixture was heated at reflux overnight. A solution of saturated ammonium chloride was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with saturated aqueous sodium carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.160 g).

Source