Hydrochloric Acid → 2-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propylamino)-N,N-dimethylnicotinamide hydrochloride

HRID 2294134Notes

Reaction equation

HRID 2294134 reaction equation
[Cl:1][C:2]1[N:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][NH2:30])[CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].Cl>C(O)C.O>[ClH:1].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]1[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][CH2:29][NH:30][C:2]2[N:12]=[CH:11][CH:10]=[CH:9][C:3]=2[C:4]([N:6]([CH3:8])[CH3:7])=[O:5])[CH2:25][CH2:26]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 104672591-(3-Aminopropyl)-4-(2-methoxyphenyl)piperazineHCID 109652142-chloro-N,N-dimethylpyridine-3-carboxamide

Product 1

HCID 214734702-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propylamino)-N,N-dimethylnicotinamide hydrochlorideYield 66.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-chloro-N,N-dimethylnicotinamide (174.3 g, 0.94 mmol), prepared as in Example 13, 3-[4-(2-methoxyphenyl)piperazin-1-yl]propylamine (224 g, 0.9 mmol), prepared as in Example 7, and potassium carbonate (250.5 g, 1.81 mmol) in 4 L of xylenes was heated at gentle reflux (133° to 136° C.) for 39 hours. The mixture was allowed to cool to 50° C. and then 1 L of water was added. The organic layer was separated, washed with water (2×500 mL) and concentrated under reduced pressure. The residue was dissolved in 6 L of ethyl acetate and the solution was washed with water (3×1 L) and saturated sodium chloride (2×250 mL), dried (MgSO4) and filtered. The filter was rinsed with 1 L of ethyl acetate and the combined filtrate was concentrated to approximately 4.8 L. A solution of 3.8N hydrochloric acid (175 mL, 0.67 mmol) in ethanol was added and the mixture was aged at room temperature for 90 minutes and then filtered. The filtered residue was washed with ethyl acetate (4×500 mL), dried under reduced pressure at 79° C. for 18 hours to give 2-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propylamino}-N,N-dimethylnicotinamide hydrochloride (259.4 g, 0.6 mmol), m.p. 204°-206° C. Anal.: Calcd. for C22H31N5O2.HCl: C, 60.89; H, 7.43; N, 16.14%; Found: C, 61.14; H, 7.46; N, 15.96%.

Workup

  1. temperaturewas heated
  2. temperatureat gentle reflux (133° to 136° C.) for 39 hours
  3. customThe organic layer was separated
  4. washwashed with water (2×500 mL)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in 6 L of ethyl acetate
  7. washthe solution was washed with water (3×1 L) and saturated sodium chloride (2×250 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. washThe filter was rinsed with 1 L of ethyl acetate
  11. concentrationthe combined filtrate was concentrated to approximately 4.8 L
  12. filtrationfiltered
  13. washThe filtered residue was washed with ethyl acetate (4×500 mL)
  14. customdried under reduced pressure at 79° C. for 18 hours

Sources & evidence

ORD record
ord-aeb2a603e5714ab3b6608e77bf1633eb
Source dataset
uspto-grants-1997_11
Patent number
US05688795

Reaction notes

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