1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(3-Iodo-4-methylphenyl)-6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazole

HRID 706802Notes

Reaction equation

HRID 706802 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[NH2:16])[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]1.[I:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[CH3:27])[C:21](O)=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CC(O)=O>[I:17][C:18]1[CH:19]=[C:20]([C:21]2[NH:1][C:2]3[CH:3]=[C:4]([CH2:5][N:6]4[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]4)[CH:13]=[CH:14][C:15]=3[N:16]=2)[CH:24]=[CH:25][C:26]=1[CH3:27]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6216403-Iodo-4-methylbenzoic acidHCID 591273961-(3,4-Diaminobenzyl)-4-methylpiperazine

Product 1

HCID 867095552-(3-Iodo-4-methylphenyl)-6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazoleYield 30.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(3,4-diaminobenzyl)-4-methylpiperazine (10 mmol), 3-iodo-4-methylbenzoic acid (2.6 g, 10 mmol), EDCI (11 mmol), and HOBt (11 mmol) in dry DMF (25 mL) was stirred at ambient temperature for 24 hrs. The mixture was then evaporated in vacuo and the crude residue was dissolved in CH2Cl2 (100 mL) was washed with water (100 mL), brine (100 mL) and then dried by Na2SO4, filtered and concentrated. The residue obtained was dissolved in AcOH (30 mL) and heated at reflux for 3 hrs. The reaction mixture was eavporated in vacuo and the residue was purified by silica gel chromatography (eluent: 10% MeOH in CH2Cl2, MeOH was added 0.5% Et3N) to give a yellow solid (1.35 g, 30.3%). 1H NMR (300 MHz, CDCl3) δ: 8.50 (1 H, s), 7.94-7.97 (1 H, d, J=9.0 Hz), 7.53-7.56 (1 H, d, J=9.0 Hz), 7.52-7.55 (1 H, d, J=9.0 Hz), 7.30 (1 H, s), 7.20-7.23 (1 H, d, J=9.0 Hz), 3.60 (2 H, s), 2.54 (8 H, brs), 2.45 (3 H, s), 2.32 (3 H, s).

Workup

  1. customThe mixture was then evaporated in vacuo
  2. dissolutionthe crude residue was dissolved in CH2Cl2 (100 mL)
  3. washwas washed with water (100 mL), brine (100 mL)
  4. dry with materialdried by Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue obtained
  8. temperatureheated
  9. temperatureat reflux for 3 hrs
  10. customthe residue was purified by silica gel chromatography (eluent: 10% MeOH in CH2Cl2, MeOH was added 0.5% Et3N)

Sources & evidence

ORD record
ord-36edb0fc5f8e44478f79d6dd0cf3d422
Source dataset
uspto-grants-2015_11
Patent number
US09174996B2

Reaction notes

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