Methanol → HCID 22285561, compound

HRID 1062446Notes

Reaction equation

HRID 1062446 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)[CH:10]=[C:11]([C:13]([NH:15][CH:16]2[CH2:21][CH2:20][N:19](C(OCC)=O)[CH2:18][CH2:17]2)=[O:14])[N:12]=1.[Si](I)(C)(C)C.CO.C[O-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:27]2[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=2)[CH:10]=[C:11]([C:13]([NH:15][CH:16]2[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]2)=[O:14])[N:12]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 85247Trimethylsilyl iodideHCID 10942334Sodium MethoxideHCID 22285503HCID 22285503, compound

Product 1

HCID 22285561HCID 22285561, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 4-({[2-(2-chlorophenyl)-1-(4-chlorophenyl)-1H-imidazol-4-yl]carbonyl}amino)-1-piperidinecarboxylate (Table entry 221) (0.595 g, 1.221 mmol) in CH2Cl2 (10 mL) was added TMSI (0.176 mL, 2.7 mmol). The mixture was heated at reflux for 3 h, diluted by methanol, and concentrated. The residue was dissolved in methanol and NaOMe (0.62 mmol) was added. The mixture was concentrated and purified by flash chromatography (2M NH3 in methanol:EtOAc=15:85) to afford the product 2-(2-chlorophenyl)-1-(4-chlorophenyl)-N-(4-piperidinyl)-1H-imidazole-4-carboxamide (180 mg, 36% yield): LC-MS m/z 415.3 (MH+), retention time 2.22 min (method 1); Rf=0.25 (1:1 EtOAc/2M NH3 in MeOH). 1H NMR (300 MHz, CDCl3) δ 1.35-1.51 (2H, m), 1.91-2.15 (3H, br), 2.63-2.78 (2H, m), 3.03-3.09 (2H, m), 3.97-4.15 (1H, m), 6.96-7.52 (8H, m), 7.81 (1H, s).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 h
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in methanol
  5. concentrationThe mixture was concentrated
  6. custompurified by flash chromatography (2M NH3 in methanol:EtOAc=15:85)

Sources & evidence

ORD record
ord-8dbd69fda0c5462297a8f0880119b766
Source dataset
uspto-grants-2005_11
Patent number
US06960601B2

Reaction notes

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