反応 #3328

反応方程式

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

溶媒

dimethylformamide

dimethylformamide

反応条件

後処理

1. 1
   温度The mixture was heated to 70° C.
2. 2
   温度cooled to room temperature
3. 3
   その他the resulting precipitate was removed by filtration
4. 4
   洗浄washed with water
5. 5
   洗浄This solid was washed with 10% methanol in ethyl acetate
6. 6
   その他to provide 96 mg of crude product
7. 7
   濃縮The filtrate was concentrated
8. 8
   その他to provide an additional 77 mg of crude product
9. 9
   その他An analytical sample was obtained by purification by flash chromatography
10. 10
    洗浄eluting with a gradient of ethyl acetate to 10% methanol in ethyl acetate

実験手順

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.

出典