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N,N-二甲基甲酰胺 → 6-cyano-N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]nicotinamide

HRID 1664041
笔记
打印预览

反应方程式

HRID 1664041 反应方程式
Cl[C:2]1[CH:40]=[CH:39][C:5]([C:6]([NH:8][C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:25](=[O:37])[C:26]5[CH:31]=[CH:30][CH:29]=[C:28]([C:32]6([C:35]#[N:36])[CH2:34][CH2:33]6)[CH:27]=5)[CH:19]=4)=[N:13][N:12]3[CH:38]=2)=[O:7])=[CH:4][N:3]=1.C(=O)([O-])O.[Na+].[CH3:46][N:47](C)C=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N>[C:46]([C:2]1[CH:40]=[CH:39][C:5]([C:6]([NH:8][C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:25](=[O:37])[C:26]5[CH:31]=[CH:30][CH:29]=[C:28]([C:32]6([C:35]#[N:36])[CH2:34][CH2:33]6)[CH:27]=5)[CH:19]=4)=[N:13][N:12]3[CH:38]=2)=[O:7])=[CH:4][N:3]=1)#[N:47]
参与物反应条件实验过程后处理来源与证据反应笔记

参与物

6

反应物 3

HCID 6228N,N-二甲基甲酰胺HCID 516892碳酸氢钠HCID 575057506-chloro-N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]nicotinamide

产物 1

HCID 575057656-cyano-N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]nicotinamide收率 47%

试剂、催化剂与溶剂 2

HCID 11186
氰化锌
催化剂
HCID 9811564三(二亚苄基丙酮)二钯催化剂

反应条件

温度
100 °C

实验过程

A mixture of 6-chloro-N-[6-(3-{[3-(1-cyanocyclopropyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]nicotinamide (120 mg, 0.201 mmol), tetrakis(triphenylphosphine)palladium (0) (58 mg, 50.4 mol), zinc cyanide (26 mg, 0.225 mmol) and N,N-dimethylformamide (2.5 mL) was stirred with heating under an argon atmosphere at 100° C. for 6.5 hr. After the reaction mixture was allowed to cool to room temperature, saturated aqueous sodium hydrogencarbonate solution was added to the mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) to give the title compound (51 mg, 47%) as a yellow powder.

后处理

  1. temperatureto cool to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0)

来源与证据

ORD记录
ord-3dbb07f7def143a4968bcf0b4eb6c321
来源数据集
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
专利号
US08034812B2

反应笔记

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本页导航参与物反应条件实验过程后处理来源与证据反应笔记