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

HRID 927249Notes

Reaction equation

[F:1][CH:2]([F:28])[C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[CH2:15][CH2:16][C:17](=[O:18])[C:13]=3[CH:12]([C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=3)[NH:11][C:10]2=[O:27])[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[CH3:31][S:32](Cl)(=[O:34])=[O:33]>O1CCCC1.O>[F:28][CH:2]([F:1])[C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[CH2:15][CH2:16][C:17](=[O:18])[C:13]=3[CH:12]([C:19]3[CH:20]=[CH:21][C:22]([C:23]#[N:24])=[CH:25][CH:26]=3)[N:11]([S:32]([CH3:31])(=[O:34])=[O:33])[C:10]2=[O:27])[CH:6]=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 50 °C

Procedure

4-(1-(3-(Difluoromethyl)phenyl)-2,5-dioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)benzonitrile (example 11, 100 mg, 0.26 mmol) is added to a suspension of sodium hydride (60% in mineral oil, 30 mg, 0.74 mmol) in tetrahydrofuran (3.0 mL). After 10 min methanesulfonyl chloride (42 μL, 0.55 mmol) is added and the mixture is heated at 50° C. over night. The mixture is cooled at room temperature, diluted with water (0.5 mL) and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 74 mg; ESI mass spectrum [M+H]+=458; Retention time HPLC: 0.76 min (005_CA01).

Workup

temperatureThe mixture is cooled at room temperature
custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
custom0.76 min (005_CA01)

Sources & evidence

ORD record: ord-5e7013ac423241a9b5fa22e704011cdd
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290459B1

Reaction notes

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