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

HRID 927250Notes

Reaction equation

HRID 927250 reaction equation
[H-].[Na+].[O:3]=[C:4]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[C:8]2[CH2:20][CH2:21][C:22](=[O:23])[C:7]=2[C@@H:6]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[S:32]([CH3:35])(=[O:34])=[O:33])[NH:5]1.[CH3:36][S:37](Cl)(=[O:39])=[O:38].O>O1CCCC1>[CH3:35][S:32]([C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][C:24]=1[CH:6]1[N:5]([S:37]([CH3:36])(=[O:39])=[O:38])[C:4](=[O:3])[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:17])[F:18])[CH:11]=2)[C:8]2[CH2:20][CH2:21][C:22](=[O:23])[C:7]1=2)[C:28]#[N:29])(=[O:33])=[O:34]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 77844826(S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile

Product 1

HCID 903109893-(Methylsulfonyl)-4-(3-(methylsulfonyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% in mineral oil, 20 mg, 0.50 mmol) is added to a solution of (S)-4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]-pyrimidin-4-yl)-3-(methylsulfonyl)benzonitrile (example 10A, 100 mg, 0.18 mmol based on 85% purity) in tetrahydrofuran (4.0 mL), and the mixture is stirred at room temperature for 20 min Methanesulfonyl chloride (29 μL, 0.38 mmol) is added and the mixture is stirred at room temperature for 2 h. Water is added and the mixture is extracted with dichloromethane. The phases are separated and the organic layer is concentrated under a) reduced pressure. The residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 76 mg; ESI mass spectrum [M+H]+=554; Retention time HPLC: 0.57 min (X012_S01).

Workup

  1. additionis added
  2. extractionthe mixture is extracted with dichloromethane
  3. customThe phases are separated
  4. concentrationthe organic layer is concentrated under a) reduced pressure
  5. customThe residue is purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
  6. custom0.57 min (X012_S01)

Sources & evidence

ORD record
ord-9011e79e721e48e69c24a4ac7fdf44d1
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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