2,4-Dimethoxybenzoic acid → (S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-2,4-dimethoxybenzamide

HRID 1017603

반응식

HRID 1017603 반응식
[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

참가 물질

6

반응물 3

HCID 70522,4-Dimethoxybenzoic acidHCID 8471TriethylamineHCID 11139461(S)-3-amino-5-(4-methylpiperazin-1-yl)-1,4-dihydro-2H-1-benzopyran

생성물 1

HCID 69209142(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran-3-yl]-2,4-dimethoxybenzamide수율 71%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 24386Thionyl Chloride용매

실험 절차

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)-1,4-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, M30 ). 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.

후처리

  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)

출처 및 근거

ORD 기록
ord-45c4c0f3cef04506852b26670db9398a
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479497B1

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