2,4-二甲氧基苯甲酸 → HCID 69209142，化合物

HRID 131129

反应方程式

HRID 131129 反应方程式
[CH3:1][O:2][C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O.[NH2:14][C@H:15]1[CH2:20][C:19]2[C:21]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)=[CH:22][CH:23]=[CH:24][C:18]=2[O:17][CH2:16]1.C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[CH3:31][N:28]1[CH2:29][CH2:30][N:25]([C:21]2[C:19]3[CH2:20][C@H:15]([NH:14][C:5](=[O:7])[C:4]4[CH:8]=[CH:9][C:10]([O:12][CH3:13])=[CH:11][C:3]=4[O:2][CH3:1])[CH2:16][O:17][C:18]=3[CH:24]=[CH:23][CH:22]=2)[CH2:26][CH2:27]1

参与物

6

反应物 3

HCID 70522,4-二甲氧基苯甲酸HCID 8471三乙胺HCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

产物 1

HCID 69209142HCID 69209142，化合物收率 71%

试剂、催化剂与溶剂 2

HCID 6344二氯甲烷溶剂HCID 24386氯化亚砜溶剂

实验过程

A solution of 2,4-dimethoxybenzoic acid (185 mg, 1.01 mmol) in thionyl chloride (5 mL) was heated at 55° C. for 15 min. The excess of thionyl chloride was removed in vacuo, and the residue was evaporated with two portions of toluene. The acid chloride was then dissolved in anhydrous methylene chloride (5 mL) and added to an ice-cooled solution of (S)-3-amino-5-(4-methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (228 mg, 0.920 mmol) in anhydrous methylene chloride (20 mL) with stirring. The precipitated product was dissolved by the addition of triethylamine (193 μL, 1.38 mmol) to give a clear light yellow solution. The ice-bath was removed, and the reaction mixture was stirred at room temperature for 1 h. The mixture was washed with a saturated NaHCO3 solution, dried (MgSO4), and the solvent was removed in vacuo. The residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% conc. NH3) affording 268 mg (71% yield) of the title compound as an oil: [α]21D −91° (c 1.0, chloroform); EIMS (70 eV) m/z (relative intensity) 411 (4, M+). The base (238 mg, 0.578 mmol) was dissolved in anhydrous diethyl ether (10 mL) under nitrogen and was cooled on an ice-bath. A solution of HCl in diethyl ether (3 M, 0.5 mL), diluted with diethyl ether (5 mL), was added dropwise with stirring. The HCl salt was filtered, washed with diethyl ether, and dried in vacuo affording 187 mg (69% yield) of the product as a white powder: mp sinters >44° C.

后处理

  1. customThe excess of thionyl chloride was removed in vacuo
  2. customthe residue was evaporated with two portions of toluene
  3. dissolutionThe acid chloride was then dissolved in anhydrous methylene chloride (5 mL)
  4. additionadded to an ice-
  5. customto give a clear light yellow solution
  6. customThe ice-bath was removed
  7. stirringthe reaction mixture was stirred at room temperature for 1 h
  8. washThe mixture was washed with a saturated NaHCO3 solution
  9. dry with materialdried (MgSO4)
  10. customthe solvent was removed in vacuo
  11. customThe residue was purified by column chromatography on silica (eluent: chloroform/ethanol; 92:8+0.5% conc. NH3)

来源与证据

ORD记录
ord-1e9f36a976624b3d903246727b5a1ae5
来源数据集
uspto-grants-2008_06
专利号
US07384943B2

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