Ethanol → 4-Methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-amine

HRID 527418Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527418
[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-])=O)=[CH:7][N:6]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)[CH:4]=1.CCO>[Pd].CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)[N:6]=[CH:7][C:8]=1[NH2:9]

Komponenten

5

Edukt 2

HCID 702EthanolHCID 867320291-(4-Methoxy-5-nitropyridin-2-yl)-4-methylpiperazine

Produkt 1

HCID 867320304-Methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-amineAusbeute 107,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-Chloro-4-methoxy-5-nitropyridine (Frontier Scientific, Newark, Del.; 1.02 g, 5.40 mmol) and K2CO3 (895 mg, 6.48 mmol) were purged with argon, treated with DMF (10 mL) followed by 1-methylpiperazine (0.66 mL, 5.94 mmol). The reaction mixture was then heated to 60° C. for 3 h. The reaction mixture was cooled to RT and treated with water, extracted with EtOAc (2×100 mL), washed with brine (2×25 mL) and dried over MgSO4, filtered and concentrated affording crude 1-(4-methoxy-5-nitropyridin-2-yl)-4-methylpiperazine (1.36 g, 5.39 mmol, 99% yield). m/z (ESI, +ve ion) 252.9 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.88 (1H, s), 5.97 (1H, s), 3.97 (3H, s), 3.70-3.78 (4H, m), 2.47-2.55 (4H, m), 2.36 (3H, s). Pd/C (10 wt. %, 586 mg, 0.55 mmol) and 1-(4-methoxy-5-nitropyridin-2-yl)-4-methylpiperazine (1.36 g, 5.39 mmol) were treated with EtOH (20 mL) and EtOAc (20 mL) and stirred at RT overnight (18 h) under an atmosphere of hydrogen (balloon). The reaction mixture was filtered through a pad of Celite, washed with MeOH, and concentrated to dryness affording 4-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-amine (8a) (1.22 g, 5.77 mmol, 99% yield) as a purple viscous oil. m/z (ESI, +ve ion) 223.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 7.67 (1H, s), 6.17 (1H, s), 3.87 (3H, s), 3.37-3.45 (4H, m), 3.32 (2H, br. s.), 2.51-2.60 (4H, m), 2.36 (3H, s).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered through a pad of Celite
  2. washwashed with MeOH
  3. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-056b958115ba46a4b5029410b05df1d0
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346801B2

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