Piperazine → 5-Chloro-4,6-dimethyl-2-(piperazin-1-yl)pyridine-3-carbonitrile

HRID 1775357Notes

Reaction equation

HRID 1775357 reaction equation
Cl[C:2]1[N:9]=[C:8]([CH3:10])[C:7]([Cl:11])=[C:6]([CH3:12])[C:3]=1[C:4]#[N:5].C([O-])([O-])=O.[K+].[K+].[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[Cl:11][C:7]1[C:6]([CH3:12])=[C:3]([C:4]#[N:5])[C:2]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:9][C:8]=1[CH3:10]

Participants

4

Reactant 3

HCID 4837PiperazineHCID 11430Potassium CarbonateHCID 3348522,5-Dichloro-4,6-dimethylnicotinonitrile

Product 1

HCID 898255905-Chloro-4,6-dimethyl-2-(piperazin-1-yl)pyridine-3-carbonitrileYield 93%

Conditions

Temperature
120 °C

Procedure

A mixture of 2,5-dichloro-4,6-dimethylnicotinonitrile (200 mg, 0.995 mmol), K2CO3 (275 mg, 1.990 mmol) and piperazine (5141 mg, 59.7 mmol) was heated under microwave heating at 120° C. for 15 minutes. After cooling to room temperature the mixture was partitioned between 1N HCl and DCM. The layers were separated and the aqueous layer was extracted once with DCM, basified with NaOH (4N) and extracted with DCM (4×). The combined organic layers were dried (sodium sulfate) and concentrated under reduced pressure to give 231 mg of a solid (0.922 mmol, yield 93%) MS (multi-mode) m/z=251.2 [M+1]+.

Workup

  1. temperaturewas heated under microwave
  2. temperatureAfter cooling to room temperature the mixture
  3. customwas partitioned between 1N HCl and DCM
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted once with DCM
  6. extractionextracted with DCM (4×)
  7. dry with materialThe combined organic layers were dried (sodium sulfate)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-34fe9bdd99214a1f8ea6dd5d98de2860
Source dataset
uspto-grants-2016_02
Patent number
US09260441B2

Reaction notes

Loading…