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

HRID 2216977Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]2[N:8]([C:23]3[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=3)[C:26]#[N:27])[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.[NH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CO>[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:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[N:3][CH:4]=2)[N:8]([C:23]2[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=2)[C:26]#[N:27])[C:9]1=[O:22]

Participants

Conditions

Temperature: 110 °C

Procedure

(±)-3-[7-Chloro-3-(2-fluoro-4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile (1.03 g; 2.42 mmol) (from Example 9a supra) was combined with aniline (1.00 mL; 10.97 mmol) (Aldrich) and heated at 110° C. for 1 hour. At this point, the reaction mixture was a solid mass. Methanol (75 mL) was added and the mixture was heated at 110° C. for 20 minutes with vigorous stirring (solid remained insoluble). Upon cooling, the solid was collected, washed with methanol and then ether and dried under high vacuum to give (±)-3-[3-(2-fluoro-4-methoxy-phenyl)-4-methyl-2-oxo-7-phenylamino-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile. (Yield 1.00 g; 85.6%). A portion of this material was recrystallized from dichloromethane-ether-petroleum ether for characterization and testing. (Yield 0.22 g).

Workup

temperaturethe mixture was heated at 110° C. for 20 minutes
temperatureUpon cooling
customthe solid was collected
washwashed with methanol
dry with materialether and dried under high vacuum

Sources & evidence

ORD record: ord-a2119bd1dfb946d0a999e3f9d6f0256a
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07112676B2

Reaction notes

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