Hydrazine hydrate (1:1) → Imatinib amine

HRID 1408851노트

반응식

HRID 1408851 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[NH:11][C:12]1C=[C:16]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:14][N:13]=1.O.[NH2:25]N>CO.C(OCC)(=O)C>[CH3:1][C:2]1[C:3]([NH:11][C:12]2[N:25]=[C:16]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[CH:15]=[CH:14][N:13]=2)=[CH:4][C:5]([NH2:8])=[CH:6][CH:7]=1

참가 물질

5

반응물 2

HCID 24654Hydrazine hydrate (1:1)HCID 23073499N-(5-nitro-2-methylphenyl)-4-(3-pyridinyl)-2-pyridineamine2회

생성물 1

HCID 9965429Imatinib amine수율 56.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl)pyridine-2-amine (3.07 g, 10.0 mmol), hydrazine monohydrate (1.54 g of 65% solution in water, 20.0 mmol), FeCl3 (21 mg, 0.13 mmol), and activated carbon (0.2 g) were dissolved in a mixture of methanol (200 mL) and ethyl acetate (100 mL). The reaction mixture was heated to 80° C. with stirring and maintained for 24 hours. The reaction mixture was cooled own to room temperature. The insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (150 mL) and washed with water (150×2). The organic phase was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resulting residue was purified by column chromatography (biotage: DMC/Methanol, 1-8%, 25 CV). The product was obtained (1.57 g, yield: 56.4%) as a yellow solid and 0.53 g starting material of N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl)pyridine-2-amine was recovered; 1H NMR (500 MHz, CDCl3) δ 2.28 (s, 3H), 3.68 (s, 2H), 6.45 (d, 1H), 6.95 (s, 1H), 7.02 (d, 1H), 7.18 (d, 1H), 7.45 (m, 1H), 7.35 (d, 1H), 7.65 (s, 1H), 8.37 (d, 1H), 8.52 (d, 1H), 8.74 (d, 1H), 9.28 (s, 1H). LC-MS (m/z) calculated, 277.3. found, 278.2 [M+H]+.

후처리

  1. temperaturemaintained for 24 hours
  2. temperatureThe reaction mixture was cooled own to room temperature
  3. customThe insoluble materials were removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in ethyl acetate (150 mL)
  6. washwashed with water (150×2)
  7. dry with materialThe organic phase was dried over anhydrous Na2SO4
  8. customThe solvent was removed under reduced pressure
  9. customthe resulting residue was purified by column chromatography (biotage: DMC/Methanol, 1-8%, 25 CV)
  10. customThe product was obtained (1.57 g, yield: 56.4%) as a yellow solid and 0.53 g
  11. customwas recovered

출처 및 근거

ORD 기록
ord-1dc917b1d7944abca21a33448a77925a
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921371B2

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