Water → 4-(1-(3-(Difluoromethyl)phenyl)-2,5-dioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile

HRID 927224Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

Under an atmosphere of argon, a mixture of 4-(4-bromophenyl)-1-(3-(difluoromethyl)-phenyl)-3,4,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-2,5-dione (intermediate 6, 159 mg, 367 μmol), zinc cyanide (73 mg, 620 μmol) and tetrakis(triphenylphosphine)palladium(0) (42 mg, 37 μmol) in N,N-dimethylformamide (2 mL) is heated at 110° C. for 3 h and then cooled to room temperature. Water is added and the mixture is extracted twice with dichloromethane. The residue is purified by flash chromatography on silica (gradient cyclo-hexane/ethyl acetate 7:3 to ethyl acetate). Yield: 82 mg; ESI mass spectrum: [M+H]+=380; Retention time HPLC: 0.49 min (X012_S01).

Workup

temperaturecooled to room temperature
extractionthe mixture is extracted twice with dichloromethane
customThe residue is purified by flash chromatography on silica (gradient cyclo-hexane/ethyl acetate 7:3 to ethyl acetate)
custom0.49 min (X012_S01)

Sources & evidence

ORD record: ord-a33397c607484f119aa1b2d4955c2f22
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290459B1

Reaction notes

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