Water → 4-(1-(3-(Trifluoromethyl)phenyl)-2,5-dioxo-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile

HRID 517238Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:16](=[O:18])[CH2:15][CH2:14][CH2:13][C:12]=3[N:11]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:10](=[O:29])[NH:9]2)=[C:4]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:3]=1.O.[CH3:35][N:36](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[O:29]=[C:10]1[NH:9][CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:35]#[N:36])=[CH:3][C:4]=2[S:30]([CH3:33])(=[O:31])=[O:32])[C:17]2[C:16](=[O:18])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]1[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:26])[F:28])[CH:20]=1

Participants

Conditions

Temperature: 110 °C

Procedure

Under an atmosphere of argon, a mixture of 4-(4-bromo-2-(methylsulfonyl)phenyl)-1-(3-(trifluoromethyl)phenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (intermediate 34), zinc cyanide (22 mg, 0.191 mmol) and tetrakis(triphenylphosphine)-palladium(O) (17 mg, 15 pot) in N,N-dimethylformamide (1 mL) is heated at 110° C. over night. Water is added and the mixture is filtered. The precipitate is purifed by flash chromatography on silica (gradient cyclohexane/ethyl acetate 80:20 to 50:50). Yield: 47 mg; ESI mass spectrum [M+H]+=490; Retention time HPLC: 0.98 min (Z012_S04).

Workup

filtrationthe mixture is filtered
custom0.98 min (Z012_S04)

Sources & evidence

ORD record: ord-cd3f1edd1b684d3a932aac3db6a55049
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115093B2

Reaction notes

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