1,2-Dichloroethane → N-{[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]acetyl}-4-(3-methylphenyl)-4 hydroxy piperidine

HRID 443225Notes

Reaction equation

HRID 443225 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[C:5]([C:9]2([OH:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.[C:16]([C:18]1[CH:33]=[CH:32][C:21]([CH2:22][N:23]2[C:27]([CH2:28][C:29](O)=[O:30])=[CH:26][N:25]=[CH:24]2)=[CH:20][CH:19]=1)#[N:17].C1C=C2C(N(O)N=NC2=CC=1)=O.C(N(CC)CC)C.C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[C:16]([C:18]1[CH:33]=[CH:32][C:21]([CH2:22][N:23]2[C:27]([CH2:28][C:29]([N:12]3[CH2:11][CH2:10][C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([CH3:2])[CH:4]=4)([OH:15])[CH2:14][CH2:13]3)=[O:30])=[CH:26][N:25]=[CH:24]2)=[CH:20][CH:19]=1)#[N:17]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 184336301-(4-Cyanobenzyl)imidazole-5-acetic acidHCID 211931674-(3-Methylphenyl)-4-hydroxypiperidine hydrochloride

Product 1

HCID 21193353N-{[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]acetyl}-4-(3-methylphenyl)-4 hydroxy piperidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of the piperidine hydrochloride from example 1 step G (102 mg, 0.447 mmol), [1-(4-cyanobenzyl)-1H-imidazol-5-yl]acetic acid (from step D) (127 mg, 0.447 mmol), HOOBT (73 mg, 0.447 mmol) and triethylamine (0.187 ml, 1.34 mmol) in DMF (3 ml)was added EDC (86 mg, 0.447 mmol) and the reaction stirred at room temperature for 18 hrs. The reaction was diluted with EtOAc and washed with saturated NaHCO3 solution. The organic extracts were dried (Na2SO4) and the solvent evaporated in vacuo. The residue was purified by preparative HPLC (C-18, gradient elution, 95:5 to 5:95 water: acetonitrile containing 0.1% trifluoroacetic acid). Lyophilization afforded the title compound as a white powder.

Workup

  1. washwashed with saturated NaHCO3 solution
  2. dry with materialThe organic extracts were dried (Na2SO4)
  3. customthe solvent evaporated in vacuo
  4. customThe residue was purified by preparative HPLC (C-18, gradient elution, 95:5 to 5:95 water: acetonitrile containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-6909cce3e2734710905f0c3a72f6282c
Source dataset
uspto-grants-1999_04
Patent number
US05891889

Reaction notes

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