p-Toluenesulfonic acid monohydrate → HCID 15837816, compound

HRID 1080910Notes

Reaction equation

HRID 1080910 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]2[C:22]([NH:23][C:24]([CH:26]3[CH2:28][CH2:27]3)=O)=[C:21]([CH3:29])[C:20]([Br:30])=[CH:19][N:18]=2)=[CH:11][CH:10]=1)#[N:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH:26]1([C:24]2[N:16]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[C:1]#[N:2])=[CH:10][CH:11]=3)[C:17]3=[N:18][CH:19]=[C:20]([Br:30])[C:21]([CH3:29])=[C:22]3[N:23]=2)[CH2:28][CH2:27]1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 15837815HCID 15837815, compound

Product 1

HCID 15837816HCID 15837816, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Toluene (20 ml) was added to 2.0 g (4.3 mmol) of 2-(2'-cyanobiphenyl-4-yl)methylamino-3-cyclopropane-carboxamido-5-bromo-4-methylpyridine, p-toluene sulfonic acid monohydrate (200 mg) and Molecular Sieves 4A (500 mg), followed by heating under reflux with stirring for 3 hours. The reaction solution was brought to room temperature and filtered through Celite to remove insolubles. Chloroform (100 ml) and an aqueous solution (100 ml) of sodium hydrogen-carbonate were added to the filtrate and the obtained mixture was caused liquid-liquid separation. The aqueous phase was further extracted with chloroform (50 ml) twice. The organic phases were combined, dried over anhydrous magnesium sulfate and subjected to vacuum concentration. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to give 1.7 g of 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)methyl-6-bromo-7-methyl-3H-imidazo[4,5-b]pyridine (yield 88%).

Workup

  1. temperatureby heating
  2. temperatureunder reflux
  3. customwas brought to room temperature
  4. filtrationfiltered through Celite
  5. customto remove insolubles
  6. additionChloroform (100 ml) and an aqueous solution (100 ml) of sodium hydrogen-carbonate were added to the filtrate
  7. customliquid-liquid separation
  8. extractionThe aqueous phase was further extracted with chloroform (50 ml) twice
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationsubjected to vacuum concentration
  11. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-9295351ffa6c4c4081e08e97dc4f249e
Source dataset
uspto-grants-1996_12
Patent number
US05583229

Reaction notes

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