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 2102860Notes

Reaction equation

HRID 2102860 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](=O)[CH3:26].CC1C=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]([CH3:26])=[CH:24]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 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 25%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of [1,1′]bipiperidinyl-2,4-dione (520 mg, 2.65 mmol) from Example 1 step 4 in dry toluene (25 ml) at room temperature were added 1-(2,4-dichlorophenylamino)-propan-2-one (576 mg, 2.64 mmol) from Step 1 above followed by a catalytic amount of p-TSA. The reaction mixture was boiled under reflux with a Dean-Stark trap, and 10 ml toluene was collected in the trap. One molar equivalent of p-TSA (250 mg) was added and the reaction mixture was boiled under reflux for 5.5 hours. After cooling to room temperature, the reaction mixture was evaporated and purified by flash chromatography (heptane:EtOAc gradient) to give 250 mg (25%) of the title compound as a brown solid. A parallel experiment with 1.51 g 1-(2,4-dichlorophenylamino)propan-2-one afforded 0.68 g (26%) of the product.

Workup

  1. customwas collected in the trap
  2. additionOne molar equivalent of p-TSA (250 mg) was added
  3. temperatureunder reflux for 5.5 hours
  4. customthe reaction mixture was evaporated
  5. custompurified by flash chromatography (heptane:EtOAc gradient)

Sources & evidence

ORD record
ord-7ca3e665a0d541e4913b412073e6be40
Source dataset
uspto-grants-2009_08
Patent number
US07576095B2

Reaction notes

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