p-Toluenesulfonic acid → 1-(2,4-Dichlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-4-one

HRID 1790040Notes

Reaction equation

HRID 1790040 reaction equation
[N:1]1([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:6][CH2:5][C:4](=O)[CH2:3][C:2]1=[O:8].[Cl:15][C:16]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=1[NH:23][CH2:24][C:25]([CH3:27])=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:15][C:16]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=1[N:23]1[C:4]2[CH2:5][CH2:6][N:1]([N:9]3[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3)[C:2](=[O:8])[C:3]=2[C:25]([CH3:27])=[CH:24]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acid2×HCID 22038474[1,1']Bipiperidinyl-2,4-dioneHCID 220384831-(2,4-Dichloroanilino)propan-2-one

Product 1

HCID 179552401-(2,4-Dichlorophenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-4-oneYield 43%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of 1,1′-bipiperidine-2,4-dione (Example 15) (260 mg, 1.32 mmol) in dry toluene (25 mL) at rt were added 1-[(2,4-dichlorophenyl)amino]acetone (288 mg, 1.32 mmol, prepared in a similar manner to Example 25) followed by p-TSA (p-toluenesulfonic acid) (25 mg, 0.132 mmol). The mixture was heated at reflux with a Dean-Stark trap, and 10 mL toluene was collected in the trap. Then, 1 equiv. of p-TSA (250 mg, 1.32 mmol) was added and the reaction mixture was heated at reflux for 6 h. The cooled reaction was evaporated and the residue purified by flash chromatography using 9:1 CH2Cl2/MeOH as eluant to give the title material as brown solid (215 mg, 43% yield), which was used in Example 18.

Workup

  1. customprepared in a similar manner to Example 25)
  2. temperatureThe mixture was heated
  3. customwas collected in the trap
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 6 h
  6. customThe cooled reaction
  7. customwas evaporated
  8. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-b78fc203366846e59b80989b96967b76
Source dataset
uspto-grants-2006_07
Patent number
US07071207B2

Reaction notes

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