1-Benzyl-4-piperidone → 2-Amino-6-benzyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carbonitrile

HRID 21700

Reaction equation

HRID 21700 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:15]1CCCC1.C(O[CH:23]=[C:24]([C:27]#[N:28])[C:25]#[N:26])C.C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1.O1CCOCC1>[NH2:26][C:25]1[C:24]([C:27]#[N:28])=[CH:23][C:12]2[CH2:13][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:9][CH2:10][C:11]=2[N:15]=1

Participants

7

Reactant 4

HCID 192201-Benzyl-4-piperidoneHCID 31268PyrrolidineHCID 671522-(Ethoxymethylene)propanedinitrileHCID 517165Ammonium Acetate

Product 1

HCID 110545552-Amino-6-benzyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carbonitrileYield 49.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1-benzyl-4-piperidone (26.8 g, 0.14 mole) and pyrrolidine (20 g, 0.28 mole) in toluene (300 ml) is refluxed for 4 hours with distilling off water. The reaction solution is concentrated to dryness under reduced pressure, and to the residue is added anhydrous dioxane (300 ml). To the mixture is added dropwise gradually with stirring a solution of ethoxymethylenemalononitrile (19 g, 0.16 mole) in anhydrous dioxane (40 ml) under ice-cooling. The mixture is warmed to room temperature, and stirred for one hour. To the mixture is added ammonium acetate (22 g, 0.29 mole), and the mixture is stirred at 70° C. overnight, and concentrated to dryness under reduced pressure. To the residue is added isopropanol, and the precipitate crystals are collected by filtration, washed with water, and dried to give 2-amino-6-benzyl-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carbonitrile (18.3 g, yield; 49%), which is used in the subsequent reaction without purification.

Workup

  1. distillationwith distilling off water
  2. concentrationThe reaction solution is concentrated to dryness under reduced pressure
  3. additionto the residue is added anhydrous dioxane (300 ml)
  4. additionTo the mixture is added dropwise gradually
  5. temperaturecooling
  6. stirringthe mixture is stirred at 70° C. overnight
  7. concentrationconcentrated to dryness under reduced pressure
  8. additionTo the residue is added isopropanol
  9. filtrationthe precipitate crystals are collected by filtration
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-4e755d18bdf14a1d91e4a853b88e67eb
Source dataset
uspto-grants-1995_06
Patent number
US05424434

Linked notes

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