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

HRID 517231Notes

Reaction equation

HRID 517231 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]3[C:16](=[O:18])[C:15]([CH3:20])([CH3:19])[CH2:14][CH2:13][C:12]=3[N:11]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:10](=[O:31])[NH:9]2)=[CH:4][CH:3]=1.O.[CH3:33][N:34](C)C=O>[C-]#N.[Zn+2].[C-]#N>[CH3:20][C:15]1([CH3:19])[CH2:14][CH2:13][C:12]2[N:11]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=3)[C:10](=[O:31])[NH:9][CH:8]([C:5]3[CH:4]=[CH:3][C:2]([C:33]#[N:34])=[CH:7][CH:6]=3)[C:17]=2[C:16]1=[O:18]

Participants

5

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 86732297HCID 86732297, compound2×

Product 1

HCID 867323514-(6,6-Dimethyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
110 °C

Procedure

Under an atmosphere of argon, a mixture of 4-(4-bromophenyl)-6,6-dimethyl-1-(3-(tri-fluoromethyl)phenyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (intermediate 7, 372 mg, 0.754 mmol), zinc cyanide (110 mg, 0.937 mmol) and tetrakis(triphenyl-phosphine)palladium(O) (50 mg, 43 μmol) in N,N-dimethylformamide (2 mL) is heated at 110° C. over night. Water is added and the mixture is filtered. The precipitate is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 80:20 to 60:40). Yield: 220 mg; ESI mass spectrum [M+H]+=440; Retention time HPLC: 1.26 min (Z005—001).

Workup

  1. filtrationthe mixture is filtered
  2. customThe precipitate is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 80:20 to 60:40)
  3. custom1.26 min (Z005—001)

Sources & evidence

ORD record
ord-b86d8ae4a2b44a0181d4def8c5136f15
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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