Citric Acid → N-[7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]propionamide

HRID 916218

Reaction equation

HRID 916218 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2=[C:16]([NH2:20])[N:17]([CH3:19])[N:18]=[C:11]12.C(N(CC)CC)C.[C:28](Cl)(=[O:31])[CH2:29][CH3:30].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2=[C:16]([NH:20][C:28](=[O:31])[CH2:29][CH3:30])[N:17]([CH3:19])[N:18]=[C:11]12

Participants

6

Reactant 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 221362787-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-ylamine

Product 1

HCID 22136285N-[7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]propionamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-ylamine (0.51 g) and triethylamine (0.27 mL) in dichloromethane (40 mL) at 0° C. was added propionyl chloride (0.17 mL) in dichloromethane (10 mL) dropwise over 25 minutes. The resulting mixture was stirred for an additional 1 hour at 0° C., followed by 14 hours at room temperature. The reaction mixture was then stirred with an aqueous 5% citric acid solution (40 mL) for 10 minutes. The layers were separated, and the aqueous layer was further extracted with dichloromethane (50 mL). The combined organic extracts were dried over anhydrous sodium sulfate, then decanted from the desiccating agent and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography using a dichloromethane/methanol gradient to afford N-[7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]propionamide (0.49 g) as an off white solid, ms m/z 347 (MH+).

Workup

  1. waitfollowed by 14 hours at room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was further extracted with dichloromethane (50 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  5. customdecanted from the desiccating agent
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-0e441fb74ecd47129c2c46f6008d11f5
Source dataset
uspto-grants-2007_09
Patent number
US07268146B2

Linked notes

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