Citric Acid → HCID 178481000, compound

HRID 432192Notes

Reaction equation

HRID 432192 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][C:16]4[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=4)=[CH:13][CH:12]=3)[C:3]=12.[OH-].[Na+].OO.C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:46]>O1CCOCC1.O>[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[CH2:33][CH2:34][N:35]([CH3:38])[CH2:36][CH2:37]4)[CH2:28][CH2:27]3)[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:15][C:16]4[CH:17]=[CH:18][C:19]([C:20]([NH2:21])=[O:46])=[CH:22][CH:23]=4)=[CH:24][CH:25]=3)[C:3]=12

Participants

8

Reactant 4

HCID 311Citric AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 178480998HCID 178480998, compound

Product 1

HCID 178481000HCID 178481000, compound

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

Cis-4-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzonitrile (0.200 g, 0.000394 mol) was dissolved in dioxane (3 mL), the solution of sodium hydroxide (0.15 g, 0.00197 mol) in water (2 mL) was added followed by the addition of 30% hydrogen peroxide solution in water (5 drops). The reaction mixture was heated at reflux under an atmosphere of nitrogen for 1.5 hours, cooled to ambient temperature and neutralized with 5% solution of citric acid in water. The solvents were removed under reduced pressure and the residue purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile—0.1M ammonium acetate over 25 min, 21 mL/min) to yield cis-4-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzamide (0.120 g, 0.000223 mol) as an off-white solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux under an atmosphere of nitrogen for 1.5 hours
  3. customThe solvents were removed under reduced pressure
  4. customthe residue purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile—0.1M ammonium acetate over 25 min, 21 mL/min)

Sources & evidence

ORD record
ord-938d80142b364eef8181f98ed4368b39
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

Loading…