p-Toluenesulfonic acid → 3-cyclopentyl-3-(4-(2-(4-(4-(methylsulfonyl)piperazin-1-yl)phenylamino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1876858Notes

Reaction equation

HRID 1876858 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH:13]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[CH2:14][C:15]#[N:16])[CH:12]=2)[CH:5]=[CH:4][N:3]=1.[N:22]1([C:28]2[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=2)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.C1(C)C=C[C:38]([S:41](O)(=[O:43])=[O:42])=CC=1.C(=O)([O-])[O-].[Na+].[Na+].CS(Cl)(=O)=O>O1CCOCC1.O>[CH:17]1([CH:13]([N:11]2[CH:12]=[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:32][C:31]4[CH:33]=[CH:34][C:28]([N:22]5[CH2:23][CH2:24][N:25]([S:41]([CH3:38])(=[O:43])=[O:42])[CH2:26][CH2:27]5)=[CH:29][CH:30]=4)[N:7]=3)[CH:9]=[N:10]2)[CH2:14][C:15]#[N:16])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 4229251-(4-Aminophenyl)piperazineHCID 866372883-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile

Product 1

HCID 580146523-cyclopentyl-3-(4-(2-(4-(4-(methylsulfonyl)piperazin-1-yl)phenylamino)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile (30 mg, 0.1 mmol), 4-(piperazin-1-yl)aniline (28.5 mg, 0.149 mmol), and p-toluenesulfonic acid (14 mg, 0.084 mmol) in dry 1,4-dioxane (0.8 mL) was refluxed overnight, then cooled to room temperature. To the resulting mixture was added 1.0 M sodium carbonate in water (0.8 mL), followed by methanesulfonyl chloride (0.015 mL, 0.20 mmol). The reaction was stirred at room temperature for 30 min and the phases were separated. The organic phase was purified on RP-HPLC at pH 10 to give the desired product as a racemic mixture (33 mg, 63%). LCMS (M+H) 521.1.

Workup

  1. temperaturewas refluxed overnight
  2. customthe phases were separated
  3. customThe organic phase was purified on RP-HPLC at pH 10

Sources & evidence

ORD record
ord-77d16fafda214554ab5b38a1dfce2400
Source dataset
uspto-grants-2012_11
Patent number
US08309718B2

Reaction notes

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