p-Toluenesulfonic acid → HCID 136248869, Verbindung

HRID 1519462Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1519462
[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[CH:5]=[C:6]([CH:8]=O)[CH:7]=1.[NH2:23][C:24]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:25]=1[C:26]([NH2:28])=[O:27].CC1C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+].FC(F)(F)C(O)=O>CC(N(C)C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:28][C:26](=[O:27])[C:25]3[C:24](=[CH:32][C:31]([O:33][CH3:34])=[CH:30][C:29]=3[O:35][CH3:36])[N:23]=2)[CH:5]=[C:4]([N:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)[CH:3]=1

Komponenten

7

Edukt 5

HCID 6101p-Toluenesulfonic acidHCID 6422Trifluoroacetic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86719363tert-Butyl 4-(3-Chloro-5-formylphenyl)piperazine-1-carboxylate

Produkt 1

HCID 136248869HCID 136248869, VerbindungAusbeute 29,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A solution of tert-butyl 4-(3-chloro-5-formylphenyl)piperazine-1-carboxylate (3, 0.300 g, 0.918 mmol) and 2-amino-4,6-dimethoxybenzamide (4, 0.120 g, 0.612 mmol) in DMA (4 mL) was treated with p-TsOH (0.424 g, 1.46 mmol) and NaHSO3 (0.290 g, 1.84 mmol) and then heated at 110° C. for 16 h. The reaction mixture was cooled to room temperature, trifluoroacetic acid (5 mL) was added and the mixture was heated at 70° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography eluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2. This material was further purified by reverse phase HPLC eluting with 10% to 90% CH3CN in H2O with 0.1% TFA. The product fractions were concentrated and the residue was dissolved in acetonitrile and water. The mixture was basified with concentrated NH4OH and the precipitate filtered, washed with water, and dried under vacuum to afford the title compound (0.072 g, 29%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 7.60-7.70 (m, 2H), 7.08-7.12 (m, 1H), 6.78 (d, J=2.3 Hz, 1H), 6.55 (d, J=2.3 Hz, 1H), 3.89 (s, 3H), 3.85 (s, 3H), 3.24 (t, J=5.2 Hz, 4H), 3.28 (t, J=5.2 Hz, 4H); ESI MS m/z 401 [M+H]+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturethe mixture was heated at 70° C. for 1 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with 0-100% 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2
  7. customThis material was further purified by reverse phase HPLC
  8. washeluting with 10% to 90% CH3CN in H2O with 0.1% TFA
  9. concentrationThe product fractions were concentrated
  10. dissolutionthe residue was dissolved in acetonitrile
  11. filtrationthe precipitate filtered
  12. washwashed with water
  13. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-737407a019084493a3b373221a72bfb0
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073878B2

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