Реакция #3328

Уравнение реакции

4-picolyl chloride hydrochloride

sodium

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

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

triethyl amine

NaH

→

2-amino-6-(2,6-dichlorophenyl)-8-pyridin-4-ylmethyl-8H-pyrido[2,3-d]pyrimidin-7-one

Растворители

dimethylformamide

dimethylformamide

Условия реакции

Обработка

1. 1
   ТемператураThe mixture was heated to 70° C.
2. 2
   Температураcooled to room temperature
3. 3
   Другоеthe resulting precipitate was removed by filtration
4. 4
   Промывкаwashed with water
5. 5
   ПромывкаThis solid was washed with 10% methanol in ethyl acetate
6. 6
   Другоеto provide 96 mg of crude product
7. 7
   КонцентрированиеThe filtrate was concentrated
8. 8
   Другоеto provide an additional 77 mg of crude product
9. 9
   ДругоеAn analytical sample was obtained by purification by flash chromatography
10. 10
    Промывкаeluting with a gradient of ethyl acetate to 10% methanol in ethyl acetate

Методика

To a suspension of NaH (60% in mineral oil, 32 mg) in 6 mL of dimethylformamide was added 2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8H)-one (200 mg, 0.65 mmol) and the mixture heated to 70° C. In a second flask containing triethyl amine (220 μL, 1.59 mmol) in 4 mL of dimethylformamide was added 4-picolyl chloride hydrochloride (137 mg, 0.84 mmol). This dark red mixture was added to the above solution of the sodium salt of 2-amino-6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8H)-one. The mixture was heated to 70° C., then cooled to room temperature. The mixture was poured into 20 mL of ice water, and the resulting precipitate was removed by filtration and washed with water. This solid was washed with 10% methanol in ethyl acetate to provide 96 mg of crude product. The filtrate was concentrated to provide an additional 77 mg of crude product. An analytical sample was obtained by purification by flash chromatography, eluting with a gradient of ethyl acetate to 10% methanol in ethyl acetate to provide 2-amino-6-(2,6-dichlorophenyl)-8-pyridin-4-ylmethyl-8H-pyrido[2,3-d]pyrimidin-7-one; mp 268°-270° C. dec.

Источник