聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯] → 4-{[5-({[(4-{4-[(4-Bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide

HRID 1675673笔记

反应方程式

HRID 1675673 反应方程式
[NH2:1][CH2:2][C:3]1[C:4]([NH:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([NH2:25])=[O:24])[CH2:19][CH2:18]2)=[C:5]2[CH:13]=[N:12][N:11]([CH2:14][CH3:15])[C:6]2=[N:7][C:8]=1[CH2:9][CH3:10].C(N(CC)CC)C.[Br:33][CH2:34][CH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]1[CH:51]=[CH:50][C:46]([C:47](Cl)=[O:48])=[CH:45][CH:44]=1.O>ClCCl>[Br:33][CH2:34][CH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]1[CH:44]=[CH:45][C:46]([C:47]([NH:1][CH2:2][C:3]2[C:4]([NH:16][CH:17]3[CH2:22][CH2:21][N:20]([C:23]([NH2:25])=[O:24])[CH2:19][CH2:18]3)=[C:5]3[CH:13]=[N:12][N:11]([CH2:14][CH3:15])[C:6]3=[N:7][C:8]=2[CH2:9][CH3:10])=[O:48])=[CH:50][CH:51]=1

参与物

6

反应物 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]HCID 8471三乙胺HCID 580247604-{4-[(4-Bromobutyl)oxy]butyl}benzoyl chloride2 次HCID 596832124-{[5-(Aminomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide2 次

产物 1

HCID 580247424-{[5-({[(4-{4-[(4-Bromobutyl)oxy]butyl}phenyl)carbonyl]amino}methyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide收率 68.5%

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂

反应条件

温度
0 °C

实验过程

A solution of 4-{[5-(aminomethyl)-1,6-diethyl-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-1-piperidinecarboxamide (0.21 g, 0.6 mmol, e.g. which can be as prepared in Intermediate 17) and triethylamine (0.21 ml, 1.52 mmol, 2.5 equivalents) in dichloromethane (20 ml) was stirred and cooled in an ice/water bath under an atmosphere of nitrogen. 4-{4-[(4-Bromobutyl)oxy]butyl}benzoyl chloride (0.32 g, 0.91 mmol, 1.5 equivalents, e.g. which can be as prepared in Intermediate 26) was added portion-wise over 2 minutes, and the mixture was stirred at 0° C. for 10 minutes and then at room temperature overnight. Iced water was added to the reaction mixture and the organic phase was separated and collected through a hydrophobic frit. The aqueous phase was extracted with dichloromethane (50 ml), and the combined organic extracts were evaporated to dryness to give a whitish foam. The residue was purified by passing through a 20 g silica column, eluting with a gradient of cyclohexane/ethyl acetate followed by a gradient of ethyl acetate/methanol. The fractions containing the product (obtained from 9:1 ethyl acetate/methanol) were pooled and evaporated to dryness to give the title compound as a pale yellow foam (0.27 g). LCMS showed MH+=656/658 (Bromine isotope pattern); TRET=2.88 min.

后处理

  1. temperaturecooled in an ice/water bath under an atmosphere of nitrogen
  2. customat room temperature
  3. customovernight
  4. customthe organic phase was separated
  5. customcollected through a hydrophobic frit
  6. extractionThe aqueous phase was extracted with dichloromethane (50 ml)
  7. customthe combined organic extracts were evaporated to dryness
  8. customto give a whitish foam
  9. customThe residue was purified
  10. washeluting with a gradient of cyclohexane/ethyl acetate
  11. additionThe fractions containing
  12. customthe product (obtained from 9:1 ethyl acetate/methanol)
  13. customevaporated to dryness

来源与证据

ORD记录
ord-acd23be4643849b39891fc10fae99117
来源数据集
uspto-grants-2011_08
专利号
US08003663B2

反应笔记

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