p-Toluenesulfonic acid → 1-(cyclopropylsulfonyl)-4-(4-(2-(4-(1H-pyrazol-1-yl)phenyl)aminopyrimidin-4-yl)-1H-pyrazol-1-yl)piperidin-4-ylacetonitrile

HRID 1876855Notes

Reaction equation

HRID 1876855 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([C:13]3([CH2:25][C:26]#[N:27])[CH2:18][CH2:17][N:16]([S:19]([CH:22]4[CH2:24][CH2:23]4)(=[O:21])=[O:20])[CH2:15][CH2:14]3)[CH:12]=2)[CH:5]=[CH:4][N:3]=1.[N:28]1([C:33]2[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=2)[CH:32]=[CH:31][CH:30]=[N:29]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1.C(#N)C.O>[CH:22]1([S:19]([N:16]2[CH2:17][CH2:18][C:13]([CH2:25][C:26]#[N:27])([N:11]3[CH:12]=[C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([NH:37][C:36]5[CH:35]=[CH:34][C:33]([N:28]6[CH:32]=[CH:31][CH:30]=[N:29]6)=[CH:39][CH:38]=5)[N:7]=4)[CH:9]=[N:10]3)[CH2:14][CH2:15]2)(=[O:21])=[O:20])[CH2:24][CH2:23]1

Participants

7

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 5942744-(1H-Pyrazol-1-yl)anilineHCID 86637287(4-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)piperidin-4-yl)acetonitrile

Product 1

HCID 580143331-(cyclopropylsulfonyl)-4-(4-(2-(4-(1H-pyrazol-1-yl)phenyl)aminopyrimidin-4-yl)-1H-pyrazol-1-yl)piperidin-4-ylacetonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (4-(4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)piperidin-4-yl)acetonitrile (30 mg, 0.08 mmol), 4-(1H-pyrazol-1-yl)aniline (18.9 mg, 0.119 mol), and p-toluenesulfonic acid (12 mg, 0.067 mmol) in dry 1,4-dioxane (0.6 mL) was refluxed overnight. The mixture was diluted with acetonitrile and water, purified on RP-HPLC at pH 10 to give the desired product as free base (30 mg, 72%). LCMS (M+H) 530.1.

Workup

  1. temperaturewas refluxed overnight
  2. custompurified on RP-HPLC at pH 10

Sources & evidence

ORD record
ord-6bd70efc625b401fa8f964e67645adc1
Source dataset
uspto-grants-2012_11
Patent number
US08309718B2

Reaction notes

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