Nipecotic Acid → HCID 67338599, compound

HRID 1678428Notes

Reaction equation

HRID 1678428 reaction equation
[N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1Cl.[NH2:10][CH3:11].[OH-].[Na+].[NH:14]1[CH2:19][CH2:18][CH2:17][CH:16]([C:20]([OH:22])=[O:21])[CH2:15]1.[CH3:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>O.CC#N>[CH3:11][NH:10][C:2]1[N:4]=[C:5]([N:27]2[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]2)[N:7]=[C:8]([N:14]2[CH2:19][CH2:18][CH2:17][CH:16]([C:20]([OH:22])=[O:21])[CH2:15]2)[N:1]=1

Participants

8

Reactant 5

HCID 4498Nipecotic AcidHCID 6329MethylamineHCID 7954Cyanuric chlorideHCID 14798Sodium Hydroxide2×HCID 531671-Methylpiperazine

Product 1

HCID 67338599HCID 67338599, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a suspension of cyanuric chloride (1.0 g, 4.1 mmol, 1.00 equiv) in 1:1 CH3CN:H2O at 0° C. was added NH2Me (2.0 M solution in THF, 2.0 mL, 4.1 mmol, 1.00 equiv). The pH of the reaction mixture was adjusted to a pH of 8-9 by treating with 1 N NaOH. The pH was maintained between 8 and 9 for 30 min (reaction progress was monitored by LCMS). Next 3-piperidinecarboxylic acid (0.53 g, 4.1 mmol, 1.00 equiv) was added to the reaction mixture. The pH of the reaction mixture was again maintained between 8 and 9 using 1 N NaOH. Next N-methylpiperazine (4.0 mL, 41 mmol, 10.0 equiv) was added to the reaction mixture and the mixture was heated at reflux overnight. The reaction mixture was concentrated, the crude product was dissolved in a mixture of methanol and water, and purified by HPLC to provide 0.9 g of the title compound. MS (ES+): m/e 336.2 [M+H]+.

Workup

  1. temperatureThe pH was maintained between 8 and 9 for 30 min
  2. custom(reaction progress was monitored by LCMS)
  3. temperaturethe mixture was heated
  4. temperatureat reflux overnight
  5. concentrationThe reaction mixture was concentrated
  6. dissolutionthe crude product was dissolved in a mixture of methanol and water
  7. custompurified by HPLC

Sources & evidence

ORD record
ord-3c60fe91518f44d4b421aeb217040695
Source dataset
uspto-grants-2011_08
Patent number
US08008483B2

Reaction notes

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