Hydrogen Peroxide → HCID 178476546, 화합물

HRID 432218노트

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HRID 432218 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:26]3[CH2:31][CH2:30][C@@H:29]([N:32]4[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]4)[CH2:28][CH2:27]3)[N:9]=[C:10]([C:11]3[CH:25]=[CH:24][C:14]([O:15]C4C=CC=CC=4C#N)=[CH:13][CH:12]=3)[C:3]=12.[OH-:39].[Na+].OO.[O:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>C(Cl)Cl>[C:14]([OH:43])(=[O:15])[CH3:24].[C:44]([OH:43])(=[O:39])[CH3:45].[C:48]([OH:43])(=[O:15])[CH3:47].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:26]3[CH2:31][CH2:30][C@@H:29]([N:32]4[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]4)[CH2:28][CH2:27]3)[N:9]=[C:10]([C:11]3[CH:25]=[C:45]([CH:44]=[CH:13][CH:12]=3)[O:46][C:47]3[CH:48]=[CH:12][CH:11]=[CH:10][C:3]=3[C:2]([NH2:1])=[O:39])[C:3]=12

참가 물질

6

반응물 4

HCID 784Hydrogen Peroxide2회HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 178480993HCID 178480993, 화합물

생성물 1

HCID 178476546HCID 178476546, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

A mixture of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzonitrile (0.111 g, 0.218 mmol, 1 equiv), 25% aqueous sodium hydroxide (1 mL), and 30% H2O2 (1 mL) in dioxane (1 mL) was heated at 100° C. for 16 h. An additional portion of 30% H2O2 (1 mL) was added and the reaction mixture was heated at 100° C. for 2 h. The reaction mixture was allowed to cool to ambient temperature and diluted with CH2Cl2 (15 mL). The organic portion was separated and the solvents were removed under reduced pressure to afford a pale yellow solid which was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to afford cis-2-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzamide triacetate salt as an off-white solid (0.020 g, 0.038 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 8.23 (1H, s), 7.75 (1H, d, J=7.7 Hz), 7.64 (3H, d, J=6.7 Hz), 7.56 (1H, s), 7.48 (1H, t, J=7.5 Hz), 7.27 (1H, t, J=7.4 Hz), 7.19 (2H, d, J=8.6 Hz), 7.06 (1H, d, J=7.7 Hz), 4.76-4.82 (1H, m), 2.20-2.50 (1 1H, m), 2.14 (3H, s), 2.04-2.08 (2H, m), 1.89 (9H, s), 1.58-1.70 (4H, m); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 10.79 min. MS: MH+ 527.

후처리

  1. temperaturethe reaction mixture was heated at 100° C. for 2 h
  2. temperatureto cool to ambient temperature
  3. customThe organic portion was separated
  4. customthe solvents were removed under reduced pressure
  5. customto afford a pale yellow solid which
  6. customwas purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min)
  7. customThe acetonitrile was removed in vacuo

출처 및 근거

ORD 기록
ord-2c83e230b14a4d178bf77f24607682a7
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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