反応 #71434

反応方程式

α-Chloroethyl chloroformate

8-(3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(4-methoxy-benzyl)-piperazin-1-ylmethyl]pyridin-2-yl}-amide

8-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(4-methoxybenzyl)-piperazin-1-ylmethyl]-pyridin-2-yl}-amide

→

title compound

収率 53.1%

8-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid

収率 53.1%

溶媒

THF

反応条件

後処理

1. 1
   その他quenched by addition of MeOH
2. 2
   濃縮concentrated
3. 3
   workup.DISSOLUTIONThe residue was dissolved in MeOH (5 mL)
4. 4
   温度heated
5. 5
   温度to reflux for 3 h
6. 6
   温度to cool
7. 7
   ろ過The resulting solid was collected by filtration
8. 8
   workup.ADDITIONdiluted in in DCM
9. 9
   抽出a saturated aqueous solution of NaHCO3, and extracted with DCM
10. 10
    乾燥The organic phase was dried (Na2SO4)
11. 11
    ろ過filtered
12. 12
    濃縮concentrated
13. 13
    その他The residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 91.5:7.5:1)

実験手順

α-Chloroethyl chloroformate (19 μL, 0.17 mmol) was added to a cold (−78° C.) solution of 8-(3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(4-methoxy-benzyl)-piperazin-1-ylmethyl]pyridin-2-yl}-amide (Example 116) (103 mg, 0.17 mmol) in THF (2 mL). The reaction mixture was stirred for 1 h at −78° C., quenched by addition of MeOH and concentrated. The residue was dissolved in MeOH (5 mL), heated to reflux for 3 h, allowed to cool. The resulting solid was collected by filtration, diluted in in DCM and a saturated aqueous solution of NaHCO3, and extracted with DCM. The organic phase was dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 91.5:7.5:1) followed by trituration in Et2O to afford 28 mg of the title compound as a white solid. Title compound: ESI-MS: 485.2 [M+H]+; tR=3.80 min (System 1); TLC: Rf=0.10 (DCM/MeOH/NH3aq, 91.5:7.5:1).

出典