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

HRID 1876858노트

반응식

HRID 1876858 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-77d16fafda214554ab5b38a1dfce2400
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309718B2

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