2-Methyltetrahydrofuran → tert-Butyl (4-Cyano-2-(methylsulfonyl)phenyl)(2-(3-(difluoromethyl)phenylamino)-5-oxocyclopent-1-enyl)methylcarbamate

HRID 927201Notes

Reaction equation

HRID 927201 reaction equation
[H-].[Na+].[F:3][CH:4]([F:18])[C:5]1[CH:6]=[C:7]([NH:11][C:12]2[CH2:16][CH2:15][C:14](=[O:17])[CH:13]=2)[CH:8]=[CH:9][CH:10]=1.CC1CCCO1.[C:25]([C:27]1[CH:32]=[CH:31][C:30]([N:33]([CH2:41]S(C2C=CC=CC=2)(=O)=O)[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[C:29]([S:51]([CH3:54])(=[O:53])=[O:52])[CH:28]=1)#[N:26]>O>[C:25]([C:27]1[CH:32]=[CH:31][C:30]([N:33]([CH2:41][C:13]2[C:14](=[O:17])[CH2:15][CH2:16][C:12]=2[NH:11][C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([CH:4]([F:18])[F:3])[CH:6]=2)[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[C:29]([S:51]([CH3:54])(=[O:52])=[O:53])[CH:28]=1)#[N:26]

Participants

6

Reactant 4

HCID 73012-MethyltetrahydrofuranHCID 24758Sodium hydrideHCID 86732345tert-Butyl (4-Cyano-2-(methylsulfonyl)phenyl)(phenylsulfonyl)methylcarbamate2×HCID 903109643-(3-(Difluoromethyl)phenylamino)cyclopent-2-enone2×

Product 1

HCID 131735050tert-Butyl (4-Cyano-2-(methylsulfonyl)phenyl)(2-(3-(difluoromethyl)phenylamino)-5-oxocyclopent-1-enyl)methylcarbamate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Sodium hydride (60% in mineral oil, 106 mg, 2.67 mmol) is added in portions to a mixture of 3-(3-(difluoromethyl)phenylamino)cyclopent-2-enone (intermediate 5, 595 mg, 2.66 mmol) and 2-methyltetrahydrofuran (20 mL). After 2 h tert-butyl (4-cyano-2-(methyl-sulfonyl)phenyl)(phenylsulfonyl)methylcarbamate (intermediate 15, 1.00 g, 2.20 mmol) is added, and the mixture is stirred at room temperature for 2 h. Water is added and the mixture is extracted with 2-methyltetrahydrofuran. The organic layer is dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% formic acid). Yield: 665 mg; ESI mass spectrum [M+H]+=532; Retention time HPLC: 1.13 min (Z018_S04).

Workup

  1. extractionthe mixture is extracted with 2-methyltetrahydrofuran
  2. dry with materialThe organic layer is dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% formic acid)
  5. custom1.13 min (Z018_S04)

Sources & evidence

ORD record
ord-5a92dc8ed84045e8b7601a603b3fe639
Source dataset
uspto-grants-2016_03
Patent number
US09290459B1

Reaction notes

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