Reaction #3325

Reaction equation

NaH

ethyl acetate

2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8H)-one

Methyl 4-(bromomethyl) benzoate

→

4-[2-amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-ylmethyl]-benzoic acid methyl ester

Yield 70.0%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   TemperatureThe mixture was heated at 40° C. to 50° C. for 20 minutes
2. 2
   Otherresulting in a clear solution
3. 3
   Temperaturethe reaction mixture was heated at 40° C. to 50° C. for 15 minutes
4. 4
   OtherThe resulting precipitate was removed by filtration
5. 5
   Washwashed with water
6. 6
   OtherThe solid was purified by flash chromatography
7. 7
   Washeluting with a gradient of 1:1 hexane
8. 8
   Dryingethyl acetate to 1:2 hexane: ethyl acetate, then dried in vacuo

Procedure

To a suspension of NaH (60% in mineral oil, 36 mg) in 7 mL of dimethylformamide was added 2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8H)-one (195 mg, 0.64 mmol). The mixture was heated at 40° C. to 50° C. for 20 minutes, resulting in a clear solution. Methyl 4-(bromomethyl) benzoate (206 mg, 0.90 mmol) was added, and the reaction mixture was heated at 40° C. to 50° C. for 15 minutes, then poured onto 30 mL of ice water. The resulting precipitate was removed by filtration and washed with water. The solid was purified by flash chromatography, eluting with a gradient of 1:1 hexane:ethyl acetate to 1:2 hexane: ethyl acetate, then dried in vacuo to provide 204 mg of 4-[2-amino-6-(2,6-dichlorophenyl)-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-ylmethyl]-benzoic acid methyl ester containing 0.16 equivalents of ethyl acetate; mp 235°-237° C.

Source