Aniline → (+/-)-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

HRID 2216974Notes

Reaction equation

HRID 2216974 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:9](=[O:22])[N:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=3[F:21])[CH:11]([CH3:12])[C:5]2=[CH:4][N:3]=1.[NH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[F:21][C:14]1[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[CH:18][C:13]=1[N:10]1[CH:11]([CH3:12])[C:5]2[C:6](=[N:7][C:2]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:3][CH:4]=2)[N:8]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:9]1=[O:22]

Participants

3

Reactant 2

HCID 6115AnilineHCID 10431009(+/-)-7-chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Product 1

HCID 10072709(+/-)-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one

Conditions

Temperature
110 °C

Procedure

(±)-7-Chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (0.21 g; 0.53 mmol) (from Example 8c supra) and aniline (450 μL; 4.94 mmol) (Aldrich) were combined and heated at 110° C. for 1 hour. After cooling, the mixture was triturated with hexanes. The solid residue was dissolved in dichloromethane and washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification by flash chromatography (Biotage 12M; 40:60 to 50:50 ethyl acetate-hexanes gradient) and then crystallization from dichloromethane-ether gave (±)-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-1-phenyl-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a white solid. (Yield 0.20 g; 81.4%).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was triturated with hexanes
  3. dissolutionThe solid residue was dissolved in dichloromethane
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography (Biotage 12M; 40:60 to 50:50 ethyl acetate-hexanes gradient)
  9. customcrystallization from dichloromethane-ether

Sources & evidence

ORD record
ord-72a67fca1d714d27a310657db977cda2
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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