4-Bromobenzene-1,2-diamine → 6-Bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole

HRID 2400577Notes

Reaction equation

HRID 2400577 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([CH:15]=O)[CH:3]=1.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([NH2:25])[CH:19]=1.S(=O)(O)[O-].[Na+]>CN(C=O)C.O>[Br:17][C:18]1[CH:23]=[CH:22][C:21]2[N:24]=[C:15]([C:4]3[CH:3]=[C:2]([CH3:1])[N:6]([CH2:7][C:8]4[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=4)[N:5]=3)[NH:25][C:20]=2[CH:19]=1

Participants

6

Reactant 3

HCID 3235934-Bromobenzene-1,2-diamineHCID 23665763Sodium BisulfiteHCID 595046335-Methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbaldehyde

Product 1

HCID 1358759796-Bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbaldehyde (Step 2, 700 mg, 3.27 mmol) in DMF (25 mL) was added 4-bromo-o-phenylenediamine (1.2 g, 6.53 mmol) followed by sodium bisulfite (679 mg, 6.53 mmol), and the resulting mixture was heated at 110° C. for 5 h. After being cooled to rt, the reaction mixture was diluted with water. The aqueous phase was extracted with ethyl acetate (3×50 mL), and the combined organics were washed with water (1×50 mL) and brine (1×50 mL), dried (Na2SO4), filtered, and concentrated to dryness. The crude material was then purified with an ISCO CombiFlash Companion using gradient elution from 0% to 50% EtOAc in hexanes to afford the title compound as a mixture of regioisomers as a light yellow solid (600 mg, 48%): 1H NMR (300 MHz, DMSO-d6) δ 11.76 (m, 1H), 11.60 (s, 1H), 7.35-7.77 (m, 2H), 7.27-7.30 (m, 1H), 7.13 (d, 2H), 7.04 (d, 2H), 6.69 (s, 1H), 5.36 (s, 2H), 2.27 (s, 3H), 2.24 (s, 3H); ES-MS m/z 381.20, HPLC RT (Method B) 3.20 min.

Workup

  1. temperatureAfter being cooled to rt
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×50 mL)
  3. washthe combined organics were washed with water (1×50 mL) and brine (1×50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude material was then purified with an ISCO CombiFlash Companion
  8. washelution from 0% to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-c42d8e198c4b42e18dc6ed5b218fc2a0
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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