Hydrogen Peroxide → N-{1-[3,5-bis(trifiuoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine

HRID 906326Notes

Reaction equation

HRID 906326 reaction equation
[F:1][C:2]([F:46])([F:45])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[C:33]([N:34]([CH2:37][CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)[CH2:35][CH3:36])=[CH:32][CH:31]=[C:30]([O:43][CH3:44])[N:29]=2)[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:49]([O-:52])([O-])=[O:50].[Na+].[Na+].[C:55](#N)C>[Cl-].[Cl-].[Mo+2](=O)=O>[F:46][C:2]([F:1])([F:45])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[C:33]([N:34]([CH2:37][CH:38]3[CH2:39][CH2:40][CH2:41][CH2:42]3)[CH2:35][CH3:36])=[CH:32][CH:31]=[C:30]([O:43][CH3:44])[N:29]=2)[C:16]2[N:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][S:25]([CH3:26])=[O:50])=[CH:20][N:21]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1.[F:46][C:2]([F:1])([F:45])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[C:33]([N:34]([CH2:37][CH:38]3[CH2:39][CH2:40][CH2:41][CH2:42]3)[CH2:35][CH3:36])=[CH:32][CH:31]=[C:30]([O:43][CH3:44])[N:29]=2)[C:16]2[N:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][S:49]([CH3:55])(=[O:52])=[O:50])=[CH:20][N:21]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 6342AcetonitrileHCID 24437Sodium SulfiteHCID 25012937N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine

Product 2

HCID 25012936N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfinyl)ethoxy]pyrimidin-2-amineYield 10%HCID 25013093N-{1-[3,5-bis(trifiuoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amineYield 69%

Reagents, catalysts & solvents 1

HCID 86628431Dioxomolybdenum(2+) dichlorideCatalyst

Procedure

A solution of N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (82 mg, 0.12 mmol) obtained in Example 1 in acetonitrile (3 mL) was added with molybdenum dioxide dichloride (3.6 mg, 0.018 mmol) and 30% aqueous hydrogen peroxide (55 mg, 0.49 mmol), and the mixture was stirred at room temperature for 23 hours. The reaction mixture was added with saturated aqueous sodium sulfite, and the mixture was 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=3:2) to obtain N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfinyl)ethoxy]pyrimidin-2-amine (compound of Example 2, 8.4 mg, 10%) as yellow oil, and N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-amine (compound of Example 3, 59.5 mg, 69%) as pale yellow oil.

Workup

  1. extractionthe mixture was extracted 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=3:2)

Sources & evidence

ORD record
ord-ae816b11276141d2a9447333f2f5e044
Source dataset
uspto-grants-2011_09
Patent number
US08012989B2

Reaction notes

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