Hydrogen Peroxide → HCID 178476548, compound

HRID 898045Notes

Reaction equation

HRID 898045 reaction equation
[C:1]([OH:4])(=[O:3])[CH3:2].[C:5]([OH:8])(=[O:7])[CH3:6].[C:9]([OH:12])(=[O:11])[CH3:10].[NH2:13][C:14]1[N:19]=[CH:18][N:17]=[C:16]2[N:20]([C@H:41]3[CH2:46][CH2:45][C@@H:44]([N:47]4[CH2:52][CH2:51][N:50]([CH3:53])[CH2:49][CH2:48]4)[CH2:43][CH2:42]3)[N:21]=[C:22]([C:23]3[CH:40]=[CH:39][C:26]([NH:27][C:28]4[O:29][C:30]5[CH:36]=[CH:35][C:34]([C:37]#[N:38])=[CH:33][C:31]=5[N:32]=4)=[CH:25][CH:24]=3)[C:15]=12.[OH-].[Na+].O.OO>O1CCOCC1>[C:1]([OH:4])(=[O:3])[CH3:2].[C:5]([OH:8])(=[O:7])[CH3:6].[C:9]([OH:12])(=[O:11])[CH3:10].[NH2:13][C:14]1[N:19]=[CH:18][N:17]=[C:16]2[N:20]([C@H:41]3[CH2:42][CH2:43][C@@H:44]([N:47]4[CH2:48][CH2:49][N:50]([CH3:53])[CH2:51][CH2:52]4)[CH2:45][CH2:46]3)[N:21]=[C:22]([C:23]3[CH:40]=[CH:39][C:26]([NH:27][C:28]4[O:29][C:30]5[CH:36]=[CH:35][C:34]([C:37]([NH2:38])=[O:3])=[CH:33][C:31]=5[N:32]=4)=[CH:25][CH:24]=3)[C:15]=12

Participants

6

Reactant 4

HCID 784Hydrogen Peroxide2×HCID 962WaterHCID 14798Sodium HydroxideHCID 178476547HCID 178476547, compound

Product 1

HCID 178476548HCID 178476548, compoundYield 120%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a mixture of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}anilino)-1,3-benzoxazole-5-carbonitrile triacetate (0.18 g, 0.00025 mol) in dioxane (2 mL) were added a 2N aqueous solution of sodium hydroxide (1.25 mL, 0.0025 mol) and water (0.75 mL). The mixture was stirred at room temperature for 2 minutes under the atmosphere of nitrogen before adding 30% hydrogen peroxide solution (0.2 mL). The mixture was refluxed for 5 hours, then stirred at room temperature for 18 hours. More 30% hydrogen peroxide solution (0.2 mL) was added to the mixture before refluxing for additional 6 hours, then stirred at room temperature for 2 days. The organic solvent was removed under reduced pressure, and 5% citric acid solution was added to maintain pH 7. The aqueous layer was removed under reduced pressure, and the crude was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 25 min with 0.1 M ammonium acetate, 21 mL/min) to give cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}anilino)-1,3-benzoxazole-5-carboxamide triacetate (0.11 g, 0.00015 mol).

Workup

  1. temperatureThe mixture was refluxed for 5 hours
  2. stirringstirred at room temperature for 18 hours
  3. temperaturebefore refluxing for additional 6 hours
  4. stirringstirred at room temperature for 2 days
  5. customThe organic solvent was removed under reduced pressure, and 5% citric acid solution
  6. additionwas added
  7. temperatureto maintain pH 7
  8. customThe aqueous layer was removed under reduced pressure
  9. customthe crude was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 25 min with 0.1 M ammonium acetate, 21 mL/min)

Sources & evidence

ORD record
ord-d2affe0c21aa48f38959e191bf951986
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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