Hydrogen Peroxide → (+/-)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzamide

HRID 1247650Notes

Reaction equation

HRID 1247650 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:18]([CH3:19])[C:17]3[C:12](=[N:13][C:14]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH2:28][N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)[CH:22]=4)=[N:15][CH:16]=3)[N:11]([C:36]3[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=3)[C:39]#[N:40])[C:10]2=[O:44])=[CH:5][CH:4]=1.[OH-:45].[Na+].C(#N)C1C=CC=CC=1.OO>CS(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH:18]([CH3:19])[C:17]3[C:12](=[N:13][C:14]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH2:28][N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)[CH:22]=4)=[N:15][CH:16]=3)[N:11]([C:36]3[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=3)[C:39]([NH2:40])=[O:45])[C:10]2=[O:44])=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 7505BenzonitrileHCID 14798Sodium HydroxideHCID 10031292(+/-)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile

Product 1

HCID 9986131(+/-)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

(±)-3-(3-(4-Methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile (0.25 g; 0.41 mmol) (from Example 7 supra) was dissolved in dimethyl sulfoxide (2.5 mL) and the resulting solution was cooled in an ice-water bath. Aqueous sodium hydroxide (1 M; 750 μL; 0.75 mmol) was added, resulting in the precipitation of the benzonitrile. Aqueous hydrogen peroxide (30%; 130 μL; 1.27 mmol) was then added. The cooling bath was removed. The solid went back into solution and a new solid precipitated out. After 3 hours the reaction mixture was diluted with water. The solid was collected, washed with water and air-dried under the house vacuum. Purification by flash chromatography (Biotage 12S; 90:10 to 60:40 chloroform-methanol gradient) and then crystallization from methanol-ethyl acetate gave (±)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzamide as a white solid. (Yield 35.7 mg; 14.3%). A second crop was collected by addition of ether to the mother liquor. (Yield 87.8 mg; 35.1%). Melting Point: 243–251° C. HR-MS(ES+) m/z Calculated for C34H38N8O3 ([M+H]+): 607.3140; Found: 607.3144.

Workup

  1. temperaturethe resulting solution was cooled in an ice-water bath
  2. customThe cooling bath was removed
  3. customa new solid precipitated out
  4. additionAfter 3 hours the reaction mixture was diluted with water
  5. customThe solid was collected
  6. washwashed with water
  7. customair-dried under the house vacuum
  8. customPurification by flash chromatography (Biotage 12S; 90:10 to 60:40 chloroform-methanol gradient)
  9. customcrystallization from methanol-ethyl acetate

Sources & evidence

ORD record
ord-34e144733cb347518c9eff6f3e1cdf84
Source dataset
uspto-grants-2006_10
Patent number
US07129351B2

Reaction notes

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