Ketoconazole → 1-(4-acetoxybenzyl)-3-[(2R*,4S*)-4-[4-(4-acetyl pi perazin-1-yl)phenoxymethyl]-2-(2,4-dichlorophenyl)-[1,3]dioxolan-2-yl methyl]-3H-imidazol-1-ium bromide

HRID 1075422

Reaction equation

HRID 1075422 reaction equation
[C:1]([O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][Br:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[CH3:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:29][C@H:30]3[O:34][C@@:33]([C:41]4[CH:42]=[CH:43][C:44]([Cl:48])=[CH:45][C:46]=4[Cl:47])([CH2:35][N:36]4[CH:40]=[N:39][CH:38]=[CH:37]4)[O:32][CH2:31]3)=[CH:26][CH:27]=2)[CH2:18][CH2:17]1)=[O:15]>C(Cl)(Cl)Cl>[Br-:10].[C:1]([O:4][C:5]1[CH:12]=[CH:11][C:8]([CH2:9][N+:39]2[CH:38]=[CH:37][N:36]([CH2:35][C@@:33]3([C:41]4[CH:42]=[CH:43][C:44]([Cl:48])=[CH:45][C:46]=4[Cl:47])[O:34][C@@H:30]([CH2:29][O:28][C:25]4[CH:24]=[CH:23][C:22]([N:19]5[CH2:20][CH2:21][N:16]([C:14](=[O:15])[CH3:13])[CH2:17][CH2:18]5)=[CH:27][CH:26]=4)[CH2:31][O:32]3)[CH:40]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 47576KetoconazoleHCID 109987714-(Bromomethyl)phenyl acetate

Product 1

HCID 443265681-(4-acetoxybenzyl)-3-[(2R*,4S*)-4-[4-(4-acetyl pi perazin-1-yl)phenoxymethyl]-2-(2,4-dichlorophenyl)-[1,3]dioxolan-2-yl methyl]-3H-imidazol-1-ium bromideYield 76%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 28 mg of 4-acetoxybenzyl bromide in 1.5 mL of CHCl3 was added 30 mg of Ketoconazole and the mixture was stirred for 16 h at room temperature. The solvent was evaporated in vacuo. Column chromatography on silica gel(Wakogel C-200, solvent:CH2Cl2/MeOH=10/1) gave 1-(4-acetoxybenzyl)-3-[(2R*,4S*)-4-[4-(4-acetyl pi perazin-1-yl)phenoxymethyl]-2-(2,4-dichlorophenyl)-[1,3]dioxolan-2-yl methyl]-3H-imidazol-1-ium bromide (32 mg, 76%, as colorless oil); MALDI-TOF-MS m/z 679 (M--Br)+; 1H-NMR(CDCl3) δ2.14(3H,s), 2.28(3H,s), 3.05(4H,m), 3.60~3.89(8H,m), 4.33(1H,m), 4.80(2H,s), 5.37(1H,d,J=14.5 Hz), 5.61(1H,d,J=14.5 Hz), 6.78(2H,d,J=9.1 Hz), 6.92, (2H,d,J=9.1 Hz), 7.03(2H,d,J=8.6 Hz), 7.24~7.63(7H,m), 10.1(1H,s).

Workup

  1. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-ba92d18b79ff486e9d60bfb59bd8f79c
Source dataset
uspto-grants-1999_05
Patent number
US05900486

Linked notes

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