p-Toluenesulfonic acid monohydrate → HCID 73296874, compound

HRID 592405Notes

Reaction equation

HRID 592405 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[CH:28]=[C:27]([NH2:29])[C:26]([CH3:30])=[N:25]1.O.C1(C)C=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:29][C:27]2[C:26]([CH3:30])=[N:25][N:24]([CH3:23])[CH:28]=2)=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 44310561,3-dimethyl-1H-pyrazol-4-amineHCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 73296874HCID 73296874, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.100 g, 0.297 mmol), 1,3-dimethyl-1H-pyrazol-4-amine (0.070 g, 0.63 mmol) and p-toluenesulfonic acid monohydrate (0.006 g, 0.032 mmol) in 1,4-dioxane (1.0 mL) was stirred in the microwave at 120° C. for 2 hours. Additional 1,4-dioxane (1.5 mL) was added and the reaction mixture was stirred in the microwave at 120° C. for a further 4 hours. The reaction mixture was adsorbed onto SiO2 and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 15-100% EtOAc in petroleum benzine 40-60° C.). Fractions containing suspected product were combined and adsorbed onto silica and purified by column chromatography (Biotage Isolera, 12 g SiO2, 0-5% MeOH in DCM) to give the title compound 26 as a pale yellow solid (0.030 g, 25%). LCMS-D: rt 3.24 min; m/z 411 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred in the microwave at 120° C. for a further 4 hours
  2. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 15-100% EtOAc in petroleum benzine 40-60° C.)
  3. additionFractions containing suspected product
  4. custompurified by column chromatography (Biotage Isolera, 12 g SiO2, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-1417fb7d52a645bdb21e3612c4d2c8e2
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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