Water → HCID 22380290, compound

HRID 1988710Notes

Reaction equation

HRID 1988710 reaction equation
[CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][C:10]([NH2:12])=[CH:11][C:6]=2[N:5]=[C:4]1[CH2:13][C:14]1[N:15]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[F:26])[N:16]=[CH:17][CH:18]=1)[CH3:2].[CH2:27](OC(OCC)OCC)C.[N-:37]=[N+:38]=[N-:39].[Na+].O>C(O)(=O)C>[CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][C:10]([N:12]3[CH:27]=[N:39][N:38]=[N:37]3)=[CH:11][C:6]=2[N:5]=[C:4]1[CH2:13][C:14]1[N:15]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[F:26])[N:16]=[CH:17][CH:18]=1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 22380213HCID 22380213, compound

Product 1

HCID 22380290HCID 22380290, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
70 °C

Procedure

1-Ethyl-2-{[2-(2,5-difluorophenyl)-pyrazol-3-yl]methyl}-5-amino-1H-benzimidazole (104 mg) is treated with triethylorthoformate (4 eq) in acetic acid (10 mL) at reflux for 4 h. After concentrating the solution, acetic acid is re-added, sodium azide (4 eq) added, and the mixture heated at 70° C. for 3 h. After cooling, water (15 mL) is added and the mixture concentrated. The residue is taken up in ethyl acetate, washed with aqueous sodium bicarbonate (2×) then saturated aqueous sodium chloride, dried (MgSO4), concentrated, and purified by preparative silica gel chromatography to give 1-ethyl-2-{[2-(2,5-difluorophenyl)-pyrazol-3-yl]methyl}-5-(1,2,3,4-tetrazol-1-yl)-1H-benzimidazole, which is converted to the hydrochloride salt in ethyl acetate. LCMS MH+ 395.018

Workup

  1. temperatureat reflux for 4 h
  2. concentrationAfter concentrating the solution, acetic acid
  3. additionis re-added
  4. temperatureAfter cooling
  5. concentrationthe mixture concentrated
  6. washwashed with aqueous sodium bicarbonate (2×)
  7. dry with materialsaturated aqueous sodium chloride, dried (MgSO4)
  8. concentrationconcentrated
  9. custompurified by preparative silica gel chromatography

Sources & evidence

ORD record
ord-a3e20b18c21c41e48b7b3c1a6c142e4b
Source dataset
uspto-grants-2010_01
Patent number
US07642267B2

Reaction notes

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