羟辛可芬 → Talnetant

HRID 276961

反应方程式

HRID 276961 反应方程式
[OH:1][C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:4][C:5]2[C:10]([C:11]=1[C:12](O)=[O:13])=[CH:9][CH:8]=[CH:7][CH:6]=2.ON1C2C=CC=CC=2N=N1.[C:31]1([C@@H:37]([NH2:40])[CH2:38][CH3:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.O.C1COCC1.CC#N>[CH2:38]([C@H:37]([NH:40][C:12]([C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:2]=1[OH:1])=[O:13])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:39]

参与物

8

反应物 4

HCID 10239羟辛可芬HCID 10868N,N'-二环己基碳二亚胺HCID 757711-羟基苯并三唑(HOBT)HCID 6993773(S)-(-)-1-苯丙胺

产物 1

HCID 5311424Talnetant收率 48.7%

试剂、催化剂与溶剂 3

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6344二氯甲烷溶剂2 次HCID 22177404Acetonitrile tetrahydrofuran溶剂

实验过程

2.49 g (9.4 mmols) of 3-hydroxy-2-phenyl-4-quinoline carboxylic acid (CAS [485-89-2]) were suspended in 150 ml of a mixture of THF/MeCN 7:3, respectively; 1.40 g (10.3 mmols) of 1-hydroxybenzotriazole (HOBT) were added to the suspension and then 1.27 g (9.4 mmols) of (S)-(−)-1-phenylpropylamine, dissolved in 20 ml of methylene chloride were added dropwise over 10 minutes period. The reaction mixture was stirred at room temperature for 30 minutes and then 2.13 g (10.3 mmols) of dicyclohexylcarbodiimide (DCC), dissolved in 20 ml of methylene chloride, were added dropwise and the reaction stirred overnight. 20 ml of H2O were added and the reaction stirred 30 minutes, then the solvent was evaporated in vacuo to dryness. The residue was taken up in EtOAc, the precipitated dicyclohexylurea (DCU) was filtered off and the filtrate washed with water, 20% citric acid, 5% NaHCO3, brine and the organic layer dried over Na2SO4 and the solvent evaporated in vacuo. The residue was purified by silica-gel (60-240 mesh) flash column chromatography, eluting with a mixture of hexane/EtOAc 9:1, containing increasing amounts of EtOAc, until the ratio 7:3. The purified product was crystallized from i-PrOH to yield 1.75 g of the title compound as a white solid.

后处理

  1. additionwere added dropwise over 10 minutes period
  2. additionwere added dropwise
  3. stirringthe reaction stirred overnight
  4. stirringthe reaction stirred 30 minutes
  5. customthe solvent was evaporated in vacuo to dryness
  6. filtrationthe precipitated dicyclohexylurea (DCU) was filtered off
  7. washthe filtrate washed with water, 20% citric acid, 5% NaHCO3, brine
  8. dry with materialthe organic layer dried over Na2SO4
  9. customthe solvent evaporated in vacuo
  10. customThe residue was purified by silica-gel (60-240 mesh) flash column chromatography
  11. washeluting with a mixture of hexane/EtOAc 9:1
  12. additioncontaining
  13. temperatureincreasing amounts of EtOAc
  14. customThe purified product was crystallized from i-PrOH

来源与证据

ORD记录
ord-4820ad2cc48e4e6895c4d79eaa7d6197
来源数据集
uspto-grants-2002_03
专利号
US06355654B1

关联笔记

加载中…