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氯化铵 → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-2-(trifluoromethyl)nicotinamide

HRID 1663999
笔记
打印预览

反应方程式

HRID 1663999 反应方程式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[N:11]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[N:34]=[CH:33][CH:32]=[CH:31][C:27]=1[C:28](O)=[O:29].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[Cl-].[NH4+]>CN(C)C=O>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:3]=[C:2]([NH:1][C:28](=[O:29])[C:27]5[CH:31]=[CH:32][CH:33]=[N:34][C:26]=5[C:25]([F:36])([F:24])[F:35])[CH:23]=[CH:22][CH:21]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1
参与物实验过程后处理来源与证据反应笔记

参与物

7

反应物 5

HCID 25517氯化铵HCID 757711-羟基苯并三唑(HOBT)HCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐HCID 27775472-(三氟甲基)烟酸HCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

产物 1

HCID 57505730N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-2-(trifluoromethyl)nicotinamide
收率 54%

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

To a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (95 mg, 0.307 mmol) in N,N-dimethylformamide (5 mL) were added 2-(trifluoromethyl)nicotinic acid (65 mg, 0.337 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (65 mg, 0.337 mmol) and 1-hydroxybenzotriazole (46 mg, 0.337 mmol), and the mixture was stirred at room temperature for 2 hr, heated to 50° C. and stirred for 2 hr. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer 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=20/80→100/0), and precipitated from ethyl acetate/diisopropyl ether to give the title compound (79.6 mg, 54%) as a pale-green powder.

后处理

  1. temperatureheated to 50° C.
  2. stirringstirred for 2 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0)
  9. customprecipitated from ethyl acetate/diisopropyl ether

来源与证据

ORD记录
ord-42176cba787e451785b77e5675c74492
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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本页导航参与物实验过程后处理来源与证据反应笔记