Water → 6-Bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole

HRID 2400578Notes

Reaction equation

HRID 2400578 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:14]=[C:13]([CH3:15])[N:12]([CH2:16][C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)[N:11]=3)[NH:7][C:6]=2[CH:24]=1.C(N(C(C)C)CC)(C)C.[CH3:34][Si:35]([CH3:42])([CH3:41])[CH2:36][CH2:37][O:38][CH2:39]Cl.O>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:14]=[C:13]([CH3:15])[N:12]([CH2:16][C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)[N:11]=3)[N:7]([CH2:39][O:38][CH2:37][CH2:36][Si:35]([CH3:42])([CH3:41])[CH3:34])[C:6]=2[CH:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 1358759796-Bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole

Product 1

HCID 595047146-Bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazoleYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-bromo-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1H-benzimidazole (Example 37, 600 mg, 1.57 mmol) in dichloromethane (20 mL) were added diisopropylethylamine (0.82 mL, 4.72 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (0.36 mL, 2.36 mmol) and the resulting mixture was stirred at rt for 16 h. Water was then added and the mixture was extracted with dichloromethane (1×50 mL), dried over Na2SO4, filtered and concentrated to dryness. The residue was then purified with an ISCO CombiFlash Companion using gradient elution from 0% to 30% EtOAc in hexanes to afford the title compound as a white solid (560 mg, 70%, mixture of two regioisomers): Isomer 1 (less polar): 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, 1H), 7.78 (d, 1H), 7.60-7.63 (dd, 1H), 7.31-7.36 (m, 4H), 6.95 (s, 1H), 6.34 (s, 2H), 5.57 (s, 2H), 3.61 (t, 2H), 2.50 (s, 3H), 2.46 (s, 3H), 0.91 (t, 2H), 0.00 (s, 9H); ES-MS m/z 512.21, HPLC RT (Method C) 4.05 min. Isomer 2 (more polar): 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, 1H), 7.79 (d, 1H), 7.59-7.62 (dd, 1H), 7.31-7.34 (m, 4H), 6.94 (s, 1H), 6.35 (s, 2H), 5.57 (s, 2H), 3.61 (t, 2H), 2.50 (s, 3H), 2.47 (s, 3H), 0.92 (t, 2H), 0.00 (s, 9H); ES-MS m/z 512.11, HPLC RT (Method B) 4.03 min.

Workup

  1. extractionthe mixture was extracted with dichloromethane (1×50 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe residue was then purified with an ISCO CombiFlash Companion
  6. washelution from 0% to 30% EtOAc in hexanes

Sources & evidence

ORD record
ord-c24d37ac6ae34b7488d723322ba75b67
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

Loading…