Cyclohexylamine → N-(1-cyclohexyl)-2-(2,4-dichlorophenyl)-5-methyl-1-(4-methoxyphenyl)-1H-imidazole-4-carboxamide

HRID 1025666Notes

Reaction equation

HRID 1025666 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:11]([CH3:17])=[C:12]([C:14](O)=[O:15])[N:13]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH:59]1([NH2:65])[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]1>C(#N)C>[CH:59]1([NH:65][C:14]([C:12]2[N:13]=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:10]([C:18]3[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)[C:11]=2[CH3:17])=[O:15])[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]1

Participants

6

Reactant 4

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 111997572-(2,4-dichlorophenyl)-5-methyl-1-(4-methoxyphenyl)-1H-imidazole-4-carboxylic acid

Product 1

HCID 10115332N-(1-cyclohexyl)-2-(2,4-dichlorophenyl)-5-methyl-1-(4-methoxyphenyl)-1H-imidazole-4-carboxamideYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Part C: To 2-(2,4-dichlorophenyl)-5-methyl-1-(4-methoxyphenyl)-1H-imidazole-4-carboxylic acid (1.00 gram, 2.65 mmol) in dry acetonitrile (25 mL) is successively added diisopropylethylamine (DIPEA) (1.02 mL, 2.2 molar equivalents), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (HBTU) (1.21 gram, 1.2 molar equivalents) and the resulting solution is stirred for 15 minutes. Cyclohexylamine (0.36 mL, 1.2 molar equivalents) is added. After stirring for 50 hours, the resulting mixture is concentrated in vacuo. The residue is dissolved in dichloromethane and an aqueous NaHCO3 solution is added. The dichloromethane layer is collected, dried over Na2SO4, filtered and concentrated in vacuo. The residue is further purified by column chromatography (gradient:dichloromethane=>dichloromethane/methanol=99/1 (v/v), silicagel) to give N-(1-cyclohexyl)-2-(2,4-dichlorophenyl)-5-methyl-1-(4-methoxyphenyl)-1H-imidazole-4-carboxamide (1.03 gram, 85% yield). Melting point: 160-161° C.

Workup

  1. stirringAfter stirring for 50 hours
  2. concentrationthe resulting mixture is concentrated in vacuo
  3. dissolutionThe residue is dissolved in dichloromethane
  4. additionan aqueous NaHCO3 solution is added
  5. customThe dichloromethane layer is collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is further purified by column chromatography (gradient:dichloromethane=>dichloromethane/methanol=99/1 (v/v), silicagel)

Sources & evidence

ORD record
ord-2f973933844549ccaeda584916c8519b
Source dataset
uspto-grants-2014_05
Patent number
US08729101B2

Reaction notes

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