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

HRID 527418노트

반응식

HRID 527418 반응식
[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]

참가 물질

5

반응물 2

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

생성물 1

HCID 867320304-Methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-amine수율 107.1%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-056b958115ba46a4b5029410b05df1d0
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346801B2

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