Hydrogen Peroxide → N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine

HRID 1442516Notes

Reaction equation

HRID 1442516 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][C:29]=2[N:38]([CH2:41][CH:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[CH2:39][CH3:40])[C:16]2[N:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][S:25][CH3:26])=[CH:18][N:17]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.OO.[S:51]([O-:54])([O-])=[O:52].[Na+].[Na+].[C:57](#N)C>[Cl-].[Cl-].[Mo+2](=O)=O>[F:48][C:2]([F:1])([F:47])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[CH:30][C:29]=2[N:38]([CH2:41][CH:42]2[CH2:43][CH2:44][CH2:45][CH2:46]2)[CH2:39][CH3:40])[C:16]2[N:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][S:25]([CH3:26])=[O:52])=[CH:20][N:21]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F:48][C:2]([F:1])([F:47])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[CH:30][C:29]=2[N:38]([CH2:41][CH:42]2[CH2:43][CH2:44][CH2:45][CH2:46]2)[CH2:39][CH3:40])[C:16]2[N:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][S:51]([CH3:57])(=[O:54])=[O:52])=[CH:20][N:21]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 6342AcetonitrileHCID 24437Sodium SulfiteHCID 25056258N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine

Product 2

HCID 25022380N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amineYield 81%HCID 25056259N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylsulfinyl)ethoxy]pyrimidin-2-amineYield 9%

Reagents, catalysts & solvents 1

HCID 86628431Dioxomolybdenum(2+) dichlorideCatalyst

Procedure

To a solution of N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (348 mg, 0.49 mmol) obtained in Example 1 in acetonitrile (7 mL) was added molybdenum dioxide dichloride (14.6 mg, 0.073 mmol) and 30% aqueous hydrogen peroxide (220 mg, 1.94 mmol), and the mixture was stirred at room temperature for 23 hours. The reaction mixture was added with saturated aqueous sodium sulfite, and extracted with chloroform. Then, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by preparative silica gel thin layer chromatography (hexane:acetone=2:1) to obtain N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylsulfinyl)ethoxy]pyrimidin-2-amine (compound of Example 2, 32.8 mg, 9%) as yellow oil, and N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({2-[(cyclopentylmethyl)(ethyl)amino]-5-(trifluoromethyl)phenyl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine (compound of Example 3, 295 mg, 81%) as a pale yellow oil.

Workup

  1. extractionextracted with chloroform
  2. washThen, the organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by preparative silica gel thin layer chromatography (hexane:acetone=2:1)

Sources & evidence

ORD record
ord-80bcb99dacbf4454b668a4c00750a81d
Source dataset
uspto-grants-2010_02
Patent number
US07659271B2

Reaction notes

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