Triethylamine → N-(1-acetylpiperidin-4-yl)-N'-(4-pyridyl)urea

HRID 49782Notes

Reaction equation

HRID 49782 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:16])OC2C=CC=CC=2)=[CH:3][CH:2]=1.Cl.[C:18]([N:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1)(=[O:20])[CH3:19].C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:18]([N:21]1[CH2:26][CH2:25][CH:24]([NH:27][C:8]([NH:7][C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)=[O:16])[CH2:23][CH2:22]1)(=[O:20])[CH3:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11401617Carbamic acid, 4-pyridinyl-, phenyl esterHCID 172216421-Acetyl-4-aminopiperidine hydrochloride

Product 1

HCID 9838119N-(1-acetylpiperidin-4-yl)-N'-(4-pyridyl)ureaYield 34.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of O-phenyl N-(4-pyridyl)carbamate (0.81 g) in chloroform (10 ml) were added 1-acetyl-4-aminopiperidine hydrochloride (0.68 g) and triethylamine (1.06 ml) at ambient temperature. After stirring for 1 day, the mixture changed to a solution. The solvents were removed under reduced pressure. A residue was purified by column chromatography (silica gel 100 ml, dichloromethane:methanol=10:1 to 5:1, and silica gel 50 ml, dichloromethane:methanol:aqueous ammonia=10:1:0.1). The solvents of desired fractions were removed under reduced pressure. A residue was dissolved with methanol (5 ml) and dichloromethane (5 ml), and 4N hydrogen chloride in dioxane (1.5 ml) was added to the solution. The solvents were removed under reduced pressure, and the residue was evaporated azeotropically with methanol. After crystallization from diisopropyl ether and n-hexane, N-(1-acetylpiperidin-4-yl)-N′-(4-pyridyl)urea (343 mg) was obtained.

Workup

  1. customThe solvents were removed under reduced pressure
  2. customA residue was purified by column chromatography (silica gel 100 ml, dichloromethane:methanol=10:1 to 5:1, and silica gel 50 ml, dichloromethane:methanol:aqueous ammonia=10:1:0.1)
  3. customThe solvents of desired fractions were removed under reduced pressure
  4. dissolutionA residue was dissolved with methanol (5 ml) and dichloromethane (5 ml), and 4N hydrogen chloride in dioxane (1.5 ml)
  5. additionwas added to the solution
  6. customThe solvents were removed under reduced pressure
  7. customthe residue was evaporated azeotropically with methanol
  8. customAfter crystallization from diisopropyl ether and n-hexane

Sources & evidence

ORD record
ord-7940cba463a44499914b6b971538617f
Source dataset
uspto-grants-2004_03
Patent number
US06710043B1

Reaction notes

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