Water → 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

HRID 906325Notes

Reaction equation

HRID 906325 reaction equation
[CH:1]1([CH2:6][N:7]([CH2:29][CH3:30])[C:8]2[C:9]([CH2:16][NH:17][C:18]3[N:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][S:27][CH3:28])=[CH:20][N:19]=3)=[N:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH:34]([C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=1)[CH3:35].O>CN(C)C=O>[F:43][C:42]([F:44])([F:45])[C:40]1[CH:41]=[C:36]([CH:34]([N:17]([CH2:16][C:9]2[C:8]([N:7]([CH2:6][CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:29][CH3:30])=[CH:13][CH:12]=[C:11]([O:14][CH3:15])[N:10]=2)[C:18]2[N:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][S:27][CH3:28])=[CH:20][N:19]=2)[CH3:35])[CH:37]=[C:38]([C:46]([F:47])([F:48])[F:49])[CH:39]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 129473971-(1-Bromoethyl)-3,5-bis(trifluoromethyl)benzeneHCID 67248264N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine

Product 1

HCID 25012937N-{1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amineYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of N-({3-[(cyclopentylmethyl)(ethyl)amino]-6-methoxypyridin-2-yl}methyl)-5-[2-(methylthio)ethoxy]pyrimidin-2-amine (168 mg, 0.39 mmol) in N,N-dimethylformamide (1 mL) stirred under ice cooling was added with sodium hydride (50% in oil, 24 mg, 1.4 mmol), and the mixture was stirred at 50° C. for 30 minutes. The reaction mixture was cooled to −78° C., added with a solution of 1-bromo-[3,5-bis(trifluoromethyl)phenyl]ethane (250 mg, 0.78 mmol) obtained in Step 2 in N,N-dimethylformamide (0.5 mL), and the mixture was stirred for 12 hours with warming to room temperature. The reaction mixture was added with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to obtain the target compound, 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 (88.1 mg, 34%), as pale yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled to −78° C.
  2. stirringthe mixture was stirred for 12 hours
  3. temperaturewith warming to room temperature
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-83b8283be8a740fab34f5bc96e5e7d7d
Source dataset
uspto-grants-2011_09
Patent number
US08012989B2

Reaction notes

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