p-Toluenesulfonic acid → HCID 10109388, compound

HRID 1067266Notes

Reaction equation

HRID 1067266 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[N:5]=[C:4]2[N:10]([C:14]3[C:19]([CH3:20])=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=3[CH3:22])[N:11]=[C:12]([CH3:13])[C:3]=12.[CH3:23][C:24]1C=C[C:27](S(O)(=O)=O)=[CH:28][CH:29]=1.C([NH:36]CCC)C>CS(C)=O.[Cu](Br)Br>[CH2:24]([CH:29]([NH:36][C:2]1[C:7]([CH3:8])=[C:6]([CH3:9])[N:5]=[C:4]2[N:10]([C:14]3[C:19]([CH3:20])=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=3[CH3:22])[N:11]=[C:12]([CH3:13])[C:3]=12)[CH2:28][CH3:27])[CH3:23]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 883981-Propanamine, N-ethyl-HCID 21192907HCID 21192907, compound

Product 1

HCID 10109388HCID 10109388, compound

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 4-chloro-3,5,6-trimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin (227 mg, 0.72 mmol), p-TsOH (124 mg) and ethylpropylamine (0.5 ml) in 1 ml of dimethylsulfoxide (DMSO) was heated at reflux for 4 hours (thin layer chromatography showed no reaction). Copper bromide (40 mg) was added and the reaction was heated for an additional 15 hours at reflux. The reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate (EtOAc). The organic layer was washed with brine, dried and concentrated to give a brown oil. The oil residue was purified through silica gel column chromatography using chloroform (CHCl3) and hexane in a ratio of 8:3 as eluent to give the title compound as a colorless oil. 1H NMR (CDCl3) 6.92 (s, 2H), 3.97 (d, 1H, NH), 3.56 (brs, 1H, OH), 2.70 (s, 3H), 2.43 (s, 3H), 2.29 (s, 3H), 2.18 (s, 3H), 1.89 (s, 6H), 1.4˜1.7 (m, 4H), 0.94 (t, 6H) ppm. The compound was prepared as the corresponding HCl salt as an off-white crystals after recrystallization from a solvent mixture of ethyl ether and ethyl acetate, mp 201-205° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours (thin layer chromatography
  3. customno reaction)
  4. temperaturethe reaction was heated for an additional 15 hours
  5. temperatureat reflux
  6. customThe reaction mixture was quenched with saturated ammonium chloride
  7. extractionextracted with ethyl acetate (EtOAc)
  8. washThe organic layer was washed with brine
  9. customdried
  10. concentrationconcentrated
  11. customto give a brown oil
  12. customThe oil residue was purified through silica gel column chromatography

Sources & evidence

ORD record
ord-90dcdcb4c27342eca28e4602ed5cbe8e
Source dataset
uspto-grants-2001_06
Patent number
US06248753B1

Reaction notes

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