p-Toluenesulfonic acid → Ethyl 4-(2-chlorophenyl)-4,7-dihydro-2-methyl-6-propyl-2H-pyrazolo[3,4-b]pyridine-5-carboxylate

HRID 489402

Reaction equation

HRID 489402 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]=[C:9]([C:15](=O)[CH2:16][CH2:17][CH3:18])[C:10]([O:12][CH2:13][CH3:14])=[O:11].[NH2:20][C:21]1[CH:25]=[CH:24][N:23]([CH3:26])[N:22]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:15]([CH2:16][CH2:17][CH3:18])[NH:20][C:21]2=[N:22][N:23]([CH3:26])[CH:24]=[C:25]12

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 1372541-Methyl-3-aminopyrazoleHCID 69733996Ethyl 2-(2-chlorophenyl)methylene-3-oxohexanoate

Product 1

HCID 135583757Ethyl 4-(2-chlorophenyl)-4,7-dihydro-2-methyl-6-propyl-2H-pyrazolo[3,4-b]pyridine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 1140TolueneSolvent

Procedure

A solution of ethyl 3-ketohexanoate (7.5 g), 2-chlorobenzaldehyde (6.6 g), piperidine (1.2 g) and acetic acid (2.25 g) in benzene (50 ml) was heated under reflux for 5 hours, and the reaction mixture was dehydrated using a Dean-Stark condenser. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography using an eluent (hexane-ethyl acetate (3:1)) to give ethyl 2-(2-chlorophenyl)methylen-3-oxohexanoate ((E)/(Z)=1:1 mixture) as a yellow oil. A solution of ethyl 2-(2-chlorophenyl)methylene-3-oxohexanoate ((E)/(Z)=1:1 mixture, 2.8 g), 3-amino-1-methylpyrazole (0.25 g) and p-toluenesulfonic acid (25 mg) in toluene (5 mL) and dimethylsulfoxide (0.5 mL) was heated under reflux for one day. The solvent was evaporated under reduced pressure, and the mixture was extracted with ethyl acetate (10 mL) and washed with a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to give an oil. The obtained oil was purified by silica gel column chromatography (eluent (ethyl acetate-methanol (10:1))) to give the title compound as colorless crystals.

Workup

  1. temperatureunder reflux for one day
  2. customThe solvent was evaporated under reduced pressure
  3. extractionthe mixture was extracted with ethyl acetate (10 mL)
  4. washwashed with a saturated aqueous sodium chloride solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customto give an oil
  8. customThe obtained oil was purified by silica gel column chromatography (eluent (ethyl acetate-methanol (10:1)))

Sources & evidence

ORD record
ord-74f1caa266ea4da288617841a066fc2c
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Linked notes

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