Ammonia → 5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinamine

HRID 2264371Notes

Reaction equation

HRID 2264371 reaction equation
[NH3:1].Br[C:3]1[N:8]=[CH:7][C:6]([CH2:9][N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH3:17])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1>CO>[CH2:16]([N:13]1[CH2:14][CH2:15][N:10]([CH2:9][C:6]2[CH:5]=[CH:4][C:3]([NH2:1])=[N:8][CH:7]=2)[CH2:11][CH2:12]1)[CH3:17]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 86642886Piperazine, 1-[(6-broMo-3-pyridinyl)Methyl]-4-ethyl-

Product 1

HCID 454899105-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinamineYield 54.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Add liquid ammonia (50.0 kg) to a degassed mixture of 1-(6-bromo-pyridin-3-ylmethyl)-4-ethyl-piperazine (14.2 kg), cuprous oxide (200 g), and MeOH (57 kg) at T≦40° C. Heat the mixture at 65-75° C. overnight. Cool to 20-30° C. and filter over a Celite® pad. Concentrate the filtrate and add DCM (113 kg) and adjust the pH to 12-14 with sodium hydroxide 2N (23 kg) separate the phases and wash the organic phase with DCM (58×2 kg) and combine the organic layers. Filter the mixture through Celite® and concentrate. Dissolve the residue in toluene (9.7 kg) and crystallize by the addition of MtBE (8.3 kg) to give 6.0 kg of the title compound. Obtain further purification through a toluene recrystallization. MS (ES+): m/z=221 (M+H)+.

Workup

  1. temperatureCool to 20-30° C.
  2. filtrationfilter over a Celite® pad
  3. concentrationConcentrate the filtrate
  4. additionadd DCM (113 kg)
  5. customseparate the phases
  6. washwash the organic phase with DCM (58×2 kg)
  7. filtrationFilter the mixture through Celite®
  8. concentrationconcentrate
  9. dissolutionDissolve the residue in toluene (9.7 kg)
  10. customcrystallize by the addition of MtBE (8.3 kg)

Sources & evidence

ORD record
ord-4e87e951fc5a4aa7a42029fa3c95d8cc
Source dataset
uspto-grants-2010_12
Patent number
US07855211B2

Reaction notes

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