Hydrogen Peroxide → HCID 178476546, compound

HRID 897508Notes

Reaction equation

HRID 897508 reaction equation
[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

Participants

6

Reactant 4

HCID 784Hydrogen Peroxide2×HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 178480993HCID 178480993, compound

Product 1

HCID 178476546HCID 178476546, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

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): δH 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 (11H, 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.

Workup

  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

Sources & evidence

ORD record
ord-5875fd0797df4584b0bde8e50e340940
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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