乙酸乙酯 → (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester

HRID 230374笔记

反应方程式

HRID 230374 反应方程式
[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9](=[O:18])[C:10]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])[CH2:5][CH:6]=[CH2:7].I[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH:34]([CH3:36])[CH3:35])[C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9](=[O:18])[C:10]1[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:5]/[CH:6]=[CH:7]/[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH:34]([CH3:36])[CH3:35])[C:28]2[N:29]=[CH:30][CH:31]=[CH:32][N:33]=2)=[CH:23][CH:22]=1

参与物

8

反应物 4

HCID 8857乙酸乙酯HCID 11430碳酸钾HCID 57762562(S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl esterHCID 57762606N-(4-iodophenyl)-N-isopropylpyrimidin-2-amine

产物 1

HCID 57762568(S,E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester收率 63.3%

试剂、催化剂与溶剂 3

HCID 80271三(邻甲基苯基)磷催化剂HCID 167845palladium acetate催化剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
80 °C

实验过程

Under an argon atmosphere, palladium acetate (19.9 mg) and tris(2-methylphenyl)phosphine (25.9 mg) were added to a suspension of (S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (514.4 mg), N-(4-iodophenyl)-N-isopropylpyrimidin-2-amine (577.4 mg) and potassium carbonate (352.9 mg) in DMF (6 ml), and the resulting mixture was stirred at 80° C. for 7 hours. After cooling the reaction solution to room temperature, ethyl acetate was added thereto, and the resulting mixture was washed twice with water and once with saturated brine, followed by drying the organic layers over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluent: cyclohexane/chloroform=2/1→1/1→1/3). The obtained crudely purified product was purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=6/1-4/112/1) to obtain (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(isopropyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (553.6 mg).

后处理

  1. temperatureAfter cooling the reaction solution to room temperature
  2. washthe resulting mixture was washed twice with water and once with saturated brine
  3. dry with materialby drying the organic layers over anhydrous sodium sulfate
  4. customAfter removing anhydrous sodium sulfate
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by column chromatography (silica gel, eluent: cyclohexane/chloroform=2/1→1/1→1/3)
  8. customThe obtained crudely purified product
  9. customwas purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=6/1-4/112/1)

来源与证据

ORD记录
ord-1a0084c7803f4e85906fb173dba7cfc5
来源数据集
uspto-grants-2009_07
专利号
US07566724B2

反应笔记

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