Water → HCID 90310807, compound

HRID 927229Notes

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

Participants

Conditions

Temperature: 110 °C

Procedure

Under an atmosphere of argon, a mixture of 4-(4-bromo-2-(methylthio)phenyl)-1-(3-(trifluoromethyl)phenyl)-3,4,6,7-tetrahydro-1H-cyclopenta[d]pyrimidine-2,5-dione (intermediate 25, 1.74 g, 2.8 mmol based on 80% purity), zinc cyanide (430 mg, 3.64 mmol) and tetrakis (triphenylphosphine)palladium(0) (323 mg, 0.28 mmol) in N,N-dimethylformamide (12 mL) is heated at 110° C. over night and then cooled to room temperature. Water is added, and the mixture is extracted with dichloromethane. The organic layer is concentrated under reduced pressure, and the residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3). Yield: 1.09 g. ESI mass spectrum: [M+H]+=444; Retention time HPLC: 0.58 min (X011_S03).

Workup

temperaturecooled to room temperature
extractionthe mixture is extracted with dichloromethane
concentrationThe organic layer is concentrated under reduced pressure
customthe residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% NH3)
custom0.58 min (X011_S03)

Sources & evidence

ORD record: ord-bd9c9ba8de5043b68ab3da98057322a2
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290459B1

Reaction notes

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