4-(4-Bromo-2-methoxyphenyl)-1-(3-(trifluoromethyl)phenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione → 4-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-methoxybenzonitrile

HRID 517268Notes

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]([O:30][CH3:31])[CH:3]=1.[Cu][C:33]#[N:34]>CN(C)C=O.CO.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:33]#[N:34])=[CH:3][C:4]=2[O:30][CH3:31])[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:28])([F:26])[F:27])[CH:20]=1

Participants

Conditions

Temperature: 140 °C

Procedure

Under an atmosphere of argon, a mixture of 4-(4-bromo-2-methoxyphenyl)-1-(3-(trifluoromethyl)phenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (intermediate 50, 21 mg, 42 μmol), copper(I) cyanide (10 mg, 0.11 mmol) and tetrakis(triphenylphosphine)-palladium(O) (5 mg, 4 μmol) in N,N-dimethylformamide (1 mL) is heated at 140° C. over it) night. The mixture is cooled at room temperature, diluted with methanol and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 4 mg; ESI mass spectrum [M+H]+=442; Retention time HPLC: 0.87 min (Z011_S03).

Workup

temperatureThe mixture is cooled at room temperature
custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
custom0.87 min (Z011_S03)

Sources & evidence

ORD record: ord-68c90b5b74314fe6997bb86c2f15c09b
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115093B2

Reaction notes

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