1-Ethylpiperazine → 4-(4-ethyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide

HRID 970309Notes

Reaction equation

HRID 970309 reaction equation
Cl.Cl[CH2:3][C:4]1[CH:32]=[CH:31][C:7]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[C:13]([NH:18][C:19]3[N:24]=[C:23]([C:25]4[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=4)[CH:22]=[CH:21][N:20]=3)[CH:12]=2)=[O:9])=[CH:6][CH:5]=1.[CH2:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)[CH3:34]>C(O)C>[CH2:33]([N:35]1[CH2:40][CH2:39][N:38]([CH2:3][C:4]2[CH:32]=[CH:31][C:7]([C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[C:13]([NH:18][C:19]4[N:24]=[C:23]([C:25]5[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=5)[CH:22]=[CH:21][N:20]=4)[CH:12]=3)=[O:9])=[CH:6][CH:5]=2)[CH2:37][CH2:36]1)[CH3:34]

Participants

4

Reactant 2

HCID 791961-EthylpiperazineHCID 220228514-(Chloromethyl)-N-4-methyl-3-[(4-(3-pyridinyl)-2-pyrimidinyl)amino]phenylbenzamide hydrochloride

Product 1

HCID 103010014-(4-ethyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 466 mg (1 mmol) of 4-chloromethyl-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide hydrochloride in 25 ml of dry ethanol is treated with 381 μl (3 mmol) N-ethylpiperazine and then heated under reflux for 16 hours. The yellow solution is cooled to room temperature and decanted from a small amount of a brown insoluble residue which forms on the wall of the flask. The solvent is evaporated and the residue taken up in citric acid solution (10% w/w) and washed with dichloromethane. The aqueous layer is made basic by addition of sodium bicarbonate and sodium carbonate solution and extracted three times with 150 ml of dichloromethane containing 2 ml of ethanol. The combined organic extracts are washed with conc. sodium chloride solution, dried over sodium sulfate, and evaporated. The residue was stirred with 3 ml of ethyl acetate and the crystalline product filtered and washed with a small amount of ethyl acetate to obtain 4-(4-ethyl-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide; m.p. 209.5-210.5° C.; tR (HPLC)1) 6.62 min.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 16 hours
  3. customdecanted from a small amount of a brown insoluble residue which
  4. customThe solvent is evaporated
  5. washwashed with dichloromethane
  6. additionThe aqueous layer is made basic by addition of sodium bicarbonate and sodium carbonate solution
  7. extractionextracted three times with 150 ml of dichloromethane containing 2 ml of ethanol
  8. washThe combined organic extracts are washed with conc. sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. filtrationthe crystalline product filtered
  12. washwashed with a small amount of ethyl acetate

Sources & evidence

ORD record
ord-9575e202197344059beb2a0c23ea299b
Source dataset
uspto-grants-2007_12
Patent number
US07312216B2

Reaction notes

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