Hydrogen Sulfide → N-(4-Chlorophenyl)-2-[1-(4-pyridyl)piperidin-4-ylmethyl]aminopyridine-3-carboxamide

HRID 1837172Notes

Reaction equation

HRID 1837172 reaction equation
Cl[C:2]1C=N[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.[CH3:33][N:34](C)C=O>[Cu]Br>[Cl:17][C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:8]([C:7]2[C:2]([NH:31][CH2:30][CH:27]3[CH2:26][CH2:25][N:24]([C:21]4[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=4)[CH2:29][CH2:28]3)=[N:34][CH:33]=[CH:5][CH:6]=2)=[O:9])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 402Hydrogen SulfideHCID 6228DimethylformamideHCID 10607746[1-(Pyridin-4-yl)piperidin-4-yl]methanamineHCID 121506913-chloro-N-(4-chlorophenyl)pyridine-4-carboxamide

Product 1

HCID 12990573N-(4-Chlorophenyl)-2-[1-(4-pyridyl)piperidin-4-ylmethyl]aminopyridine-3-carboxamideYield 13%

Reagents, catalysts & solvents 1

HCID 24593copper(I) bromideCatalyst

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

Sources & evidence

ORD record
ord-8e6fb9b33595407bb0f6f4aeb1e6d9c1
Source dataset
uspto-grants-2004_08
Patent number
US06780878B2

Reaction notes

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