1-Methylpiperazine → HCID 86617513, compound

HRID 2261961Notes

Reaction equation

HRID 2261961 reaction equation
[OH:1][C:2]1([C:19]2[CH:20]=[CH:21][C:22]3[N:26]=[C:25]([CH2:27][C:28]([O:30][CH2:31][CH2:32][CH2:33]Cl)=[O:29])[NH:24][C:23]=3[CH:35]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>C(#N)C>[OH:1][C:2]1([C:19]2[CH:20]=[CH:21][C:22]3[N:26]=[C:25]([CH2:27][C:28]([O:30][CH2:31][CH2:32][CH2:33][N:40]4[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]4)=[O:29])[NH:24][C:23]=3[CH:35]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 86617512HCID 86617512, compound

Product 1

HCID 86617513HCID 86617513, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-chloropropyl {6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}acetate (0.25 g, 0.51 mmol) and 1-methyl-piperazine (0.46 mL, 5.10 mmol) in acetonitrile (5.0 mL) was heated to 80° C. for 2 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The resulting crude product was purified by reverse phase preparative HPLC (CH3CN/25 mM aqueous ammonium acetate). The fractions were collected, and the solvent was concentrated. The aqueous residue was partitioned with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and brine, and dried over anhydrous sodium sulfate. Filtration and concentration gave a pale yellow residue, which was freeze-dried from a mixture of acetonitrile-water (1:1, 3.0 mL) to give 3-(4-methylpiperazin-1-yl)propyl {6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}acetate (0.12 g, 43%). 1H NMR (400 MHz, DMSO-d6): 11.50 (br.s, 1H), 7.70 (d, 1H), 7.49 (m, 3H), 7.23 (t, 1H), 7.15 (m, 6H), 6.84 (d, 1H), 4.49 (d, 1H), 4.16 (t, 4H), 4.10 (d, 1H), 3.34 (s, 6H), 2.36 (m, 3H), 2.18 (s, 3H) open, 2.16 (s, 3H) closed, 1.78 (m, 1H); MS (EI) for C31H34N6O4: 555 (MH+).

Workup

  1. customthe solvent was evaporated
  2. customThe resulting crude product was purified by reverse phase preparative HPLC (CH3CN/25 mM aqueous ammonium acetate)
  3. customThe fractions were collected
  4. concentrationthe solvent was concentrated
  5. customThe aqueous residue was partitioned with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationFiltration and concentration
  9. customgave a pale yellow residue, which
  10. dry with materialwas freeze-dried from a mixture of acetonitrile-water (1:1, 3.0 mL)

Sources & evidence

ORD record
ord-87b3b9ca8fc24d7ca7f6c031659254ec
Source dataset
uspto-grants-2010_12
Patent number
US07846959B2

Reaction notes

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