p-Toluenesulfonic acid → 1-(2-(2-(5-Chloro-2-(1-(1-methylpyrrolidin-3-yl)-1H-pyrazol-4-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592400Notes

Reaction equation

HRID 592400 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.[CH3:23][N:24]1[CH2:28][CH2:27][CH:26]([N:29]2[CH:33]=[C:32]([NH2:34])[CH:31]=[N:30]2)[CH2:25]1.CC1C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[Cl:22][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)=[N:7][C:2]([NH:34][C:32]2[CH:31]=[N:30][N:29]([CH:26]3[CH2:27][CH2:28][N:24]([CH3:23])[CH2:25]3)[CH:33]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 679816411-(1-Methyl-3-pyrrolidinyl)-1H-pyrazol-4-amineHCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 732967161-(2-(2-(5-Chloro-2-(1-(1-methylpyrrolidin-3-yl)-1H-pyrazol-4-ylamino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A stirred solution of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.085 g, 0.25 mmol), 1-(1-methylpyrrolidin-3-yl)-1H-pyrazol-4-amine A24 (0.046 g, 0.278 mmol) and TsOH (0.003 g, 0.02 mmol) in 1,4-dioxane (4 mL) was stirred at 120° C. in the microwave for 60 minutes followed by 150° C. for 2 hours and then 160° C. for 2 hours. After cooling, the solvent was removed to afford a crude red oil that was purified by flash chromatography (0-30% MeOH in DCM) followed by HPLC (Gradient: 20-100%, Acetonitrile 0.1% formic acid in water 0.1% formic acid, 12 min) to give the title compound 21 as a clear gum (0.008 g, 7% yield). LCMS-C: rt 4.34 min; m/z 466 [M+H]+.

Workup

  1. wait160° C. for 2 hours
  2. temperatureAfter cooling
  3. customthe solvent was removed
  4. customto afford a crude red oil that
  5. customwas purified by flash chromatography (0-30% MeOH in DCM)
  6. customfollowed by HPLC (Gradient: 20-100%, Acetonitrile 0.1% formic acid in water 0.1% formic acid, 12 min)

Sources & evidence

ORD record
ord-d7b00d7a255d495aa7b62ac474eff6f4
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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