三乙胺 → 8-(4-Benzyl-piperazin-1-yl)-6-bromo-quinoline

HRID 428540

反应方程式

HRID 428540 反应方程式
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([NH2:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.CCN(CC)CC.Cl.Cl[CH2:22][CH2:23][N:24]([CH2:32][CH2:33]Cl)[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CCCCO>[CH2:25]([N:24]1[CH2:32][CH2:33][N:12]([C:10]2[CH:11]=[C:2]([Br:1])[CH:3]=[C:4]3[C:9]=2[N:8]=[CH:7][CH:6]=[CH:5]3)[CH2:22][CH2:23]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

参与物

5

反应物 3

HCID 8471三乙胺HCID 936376-溴-8-氨基喹啉HCID 2777881N-苄基-双邻氯乙基氨基盐酸盐

产物 1

HCID 184140798-(4-Benzyl-piperazin-1-yl)-6-bromo-quinoline收率 33%

试剂、催化剂与溶剂 1

HCID 263丁醇溶剂

反应条件

温度
100 °C

实验过程

The free base of bis(2-chloroethyl)-benzlyamine (5.12 g, 19.3 mmol) was prepared by washing the HCl salt with 1 M NaOH (200 mL) and extracting into EtOAc. The resulting organic phases were dried over NASO4 and concentrated. To this flask was added 6-bromo-8-amino-quinoline (2.15 g, 9.6 mmol), n-BuOH (100 mL), and Et3N (4 mL, 28.9 mmol). The resulting reaction mixture was stirred at 100° C. overnight. TLC analysis showed starting amine was still present, therefore an additional portion of bis(2-chloroethyl)-benzylamine hydrochloride (5 g) was added. The reaction was heated an additional 72 hours. The cooled reaction mixture was quenched with 1 M NaOH (200 mL) and extracted into EtOAc (3×200 mL). The organic fractions were combined, dried over Na2SO4, and concentrated. The resulting gold oil was purified three times by column chromatography (40% EtOAc/hexanes) affording 1.2 g (33%) of a viscous orange oil which solidified upon standing: mp 65-68° C., MS (+) APCI m/z 382 [M+H]+.

后处理

  1. customThe free base of bis(2-chloroethyl)-benzlyamine (5.12 g, 19.3 mmol) was prepared
  2. washby washing the HCl salt with 1 M NaOH (200 mL)
  3. extractionextracting into EtOAc
  4. customThe resulting organic phases were dried over NASO4
  5. concentrationconcentrated
  6. customThe resulting reaction mixture
  7. temperatureThe reaction was heated an additional 72 hours
  8. customThe cooled reaction mixture
  9. customwas quenched with 1 M NaOH (200 mL)
  10. extractionextracted into EtOAc (3×200 mL)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customThe resulting gold oil was purified three times by column chromatography (40% EtOAc/hexanes)

来源与证据

ORD记录
ord-41dbe8d3ed704e2e91b90aabacaa93d7
来源数据集
uspto-grants-2001_11
专利号
US06313126B1

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