Hydrogen Sulfide → N-(4-Chlorophenyl)-3-[1-(4-pyridyl)piperidin-4-ylmethyl]aminopyridine-4-carboxamide

HRID 2083932Notes

Reaction equation

HRID 2083932 reaction equation
Cl[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)=[O:9].[N:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][CH:27]([CH2:30][NH2:31])[CH2:26][CH2:25]2)=[CH:20][CH:19]=1.S>CN(C)C=O.CO.[Cu]Br>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([NH:10][C:8]([C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[NH:31][CH2:30][CH:27]2[CH2:26][CH2:25][N:24]([C:21]3[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=3)[CH2:29][CH2:28]2)=[O:9])=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 402Hydrogen SulfideHCID 10607746[1-(Pyridin-4-yl)piperidin-4-yl]methanamineHCID 121506913-chloro-N-(4-chlorophenyl)pyridine-4-carboxamide

Product 1

HCID 12150692N-(4-Chlorophenyl)-3-[1-(4-pyridyl)piperidin-4-ylmethyl]aminopyridine-4-carboxamideYield 14%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-chloro-N-(4-chlorophenyl)pyridine-4-carboxamide (130 mg, 0.49 mmol), 1-(4-pyridyl)piperidine-4-methylamine (187 mg, 0.98 mmol), and copper(1) bromide (70 mg) in dimethylformamide (1 mL) was heated at 110° C. After 18 h, the mixture was diluted with MeOH, filtered, and concentrated. The residue was treated with 6:1 chloroform:water (10 mL) followed by MeOH until a homogenoeus solution resulted. The solution was treated with hydrogen sulfide(g), heated at reflux for 0.1 h, and filtered through diatomaceous earth. The filtrate was concentrated and the residue taken up in water, 1 N NaOH, and EtOAc. The aqueous layer was washed with EtOAc (3×), the combined extracts were dried (sodium sulfate), filtered and concentrated. The residue was purified by RPHPLC yielding 29 mg (13%) of the title compound as a hydrochloride salt.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. additionThe residue was treated with 6:1 chloroform
  4. customresulted
  5. temperatureheated
  6. temperatureat reflux for 0.1 h
  7. filtrationfiltered through diatomaceous earth
  8. concentrationThe filtrate was concentrated
  9. washThe aqueous layer was washed with EtOAc (3×)
  10. dry with materialthe combined extracts were dried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by RPHPLC

Sources & evidence

ORD record
ord-b94dbdaab26544aa9191122b8ec7bc26
Source dataset
uspto-grants-2004_04
Patent number
US06716839B2

Reaction notes

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