4-Methylmorpholine → 1-[(6-Chloronaphthalen-2-yl)sulfonyl]-4-[4-(pyridin-4-yl)nicotinyl]piperazine hydrochloride

HRID 352896Notes

Reaction equation

HRID 352896 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=CC(C(O)=O)=CN=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[Cl:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[CH:31]=[C:30]([S:35]([N:38]1[CH2:43]CNC[CH2:39]1)(=[O:37])=[O:36])[CH:29]=[CH:28]2.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.[CH3:62][N:63]([CH3:72])[CH2:64][CH2:65][CH2:66][N:67]=[C:68]=NCC>ClCCl.CN(C)C=O>[ClH:24].[Cl:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[CH:31]=[C:30]([S:35]([N:38]1[CH2:43][CH2:62][N:63]([CH2:64][C:65]3[C:8]([C:5]4[CH:4]=[CH:3][N:2]=[CH:7][CH:6]=4)=[CH:16][CH:68]=[N:67][CH:66]=3)[CH2:72][CH2:39]1)(=[O:36])=[O:37])[CH:29]=[CH:28]2

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22710058HCID 22710058, compoundHCID 69483715[2,4'-Bipyridine]-5-carboxylic acid hydrochloride

Product 1

HCID 177965971-[(6-Chloronaphthalen-2-yl)sulfonyl]-4-[4-(pyridin-4-yl)nicotinyl]piperazine hydrochlorideYield 115.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

In dichloromethane (10 ml), 6-(4-pyridyl)nicotinic acid hydrochloride (96 mg) and 1-[(6-chloronaphthalen-2-yl)sulfonyl]piperazine trifluoroacetate (150 mg) were suspended, followed by the addition of 1-hydroxybenzotriazole (48 mg) and N-methylmorpholine (155 μl). After the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (102 mg) under ice cooling, the resulting mixture was stirred at room temperature for 16 hours. Owing to the slow reaction, N,N-dimethylformamide (10 ml) was added to the reaction mixture and the resulting mixture was stirred for 3 days. After completion of the reaction, the solvent was distilled off. The residue was purified by chromatography on a silica gel column (1% methanol—dichloromethane). The solvent was then distilled off. To the residue, tetrahydrofuran and 1N hydrochloric acid in ethanol were added and the solid so precipitated was collected by filtration and dried, whereby the title compound (105 mg, 55%) was obtained as a colorless solid.

Workup

  1. additionwas added to the reaction mixture
  2. stirringthe resulting mixture was stirred for 3 days
  3. customAfter completion of the reaction
  4. distillationthe solvent was distilled off
  5. customThe residue was purified by chromatography on a silica gel column (1% methanol—dichloromethane)
  6. distillationThe solvent was then distilled off
  7. additionTo the residue, tetrahydrofuran and 1N hydrochloric acid in ethanol were added
  8. customthe solid so precipitated
  9. filtrationwas collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-f4dcd47ba6fb4c50b77112a00fd1da09
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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