反応 #359702

反応方程式

citric acid

4-Cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde

2-(Diethoxy-phosphoryl)-propionic acid ethyl ester

n-butyl lithium

→

8-cyclopentyl-6-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

収率 36.5%

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   workup.ADDITIONwas slowly added at −70° C
2. 2
   workup.ADDITIONthen added to the reaction mixture
3. 3
   その他the reaction
4. 4
   温度After 3 hours the reaction was warmed to room temperature
5. 5
   抽出extracted with diethyl ether
6. 6
   洗浄The organic layer was washed with brine
7. 7
   乾燥dried over MgSO4
8. 8
   ろ過filtered
9. 9
   濃縮concentrated
10. 10
    その他to give a yellow oil which
11. 11
    その他was purified by silica gel chromatography
12. 12
    workup.DISSOLUTIONThe resulting oil was dissolved to 1,8-diazabicyclo[5.4.0]undec-7-ene (75 mL)
13. 13
    温度heated to 150° C. for 4 hours
14. 14
    温度The reaction mixture was cooled to room temperature
15. 15
    workup.ADDITIONdiluted with ethyl acetate (350 mL)
16. 16
    洗浄washed with 5% HCl and brine
17. 17
    乾燥dried over MgSO4
18. 18
    ろ過filtered
19. 19
    濃縮concentrated in vacuo The remaining residue
20. 20
    workup.ADDITIONwas diluted with diethyl ether
21. 21
    ろ過the precipitated solid was filtered off

実験手順

2-(Diethoxy-phosphoryl)-propionic acid ethyl ester (15.24 g, 64 mmol) was dissolved in tetrahydrofuran (100 mL) to which n-butyl lithium (47.7 mL, 119 mmol, 2.5 M in hexanes) was slowly added at −70° C. 4-Cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde (15 g, 63 mmol) was dissolved in tetrahydrofuran (70 mL) then added to the reaction mixture allowing the reaction to warm to −40° C. After 3 hours the reaction was warmed to room temperature, poured into cold 1 N citric acid and extracted with diethyl ether. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give a yellow oil which was purified by silica gel chromatography. The resulting oil was dissolved to 1,8-diazabicyclo[5.4.0]undec-7-ene (75 mL) and heated to 150° C. for 4 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (350 mL), washed with 5% HCl and brine, dried over MgSO4, then filtered and concentrated in vacuo The remaining residue was diluted with diethyl ether and the precipitated solid was filtered off to give 8-cyclopentyl-6-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one as a white solid (6.33 g, 31.3%). 1H NMR δ(400 MHz, CDCl3) 8.52 (s, 1H), 7.39 (d, J=1.2 Hz, 1H), 5.96, (m, 1H), 2.59 (s, 3H), 2.30 (m, 2H), 2.19 (d, J=1.2 Hz, 3H), 2.07 (m, 2H), 1.86 (m, 2H), 1.67 (m, 2H).

出典