Cyclization of 2,2-dichloroisobutyraldehyde (I) - obtained by reaction of isovaleraldehyde (II) with chlorine in DMF - with 2-benzyloxyacetaldehyde (III) - produced by reaction of 2-butene-1,4-diol (IV) with benzyl chloride by means of NaOH in water, followed by ozonolysis in MeOH and finally reduction with triphenylphosphine in ethyl acetate - and aqueous NH4OH in methanol gives the imidazole derivative (VI), which is iodinated with I2 and NaOH in dichloromethane to yield the 5-iodoimidaz-ole derivative (VII). Condensation of compound (VII) with bis(3,5-dichlorophenyl)disulfide (VIII) by means of LiH in DMSO affords the dichlorophenylsulfanyl imidazole (IX), which is alkylated with 4-(chloromethyl)pyridine (X) and K2CO3 in DMF to provide the fully substituted imidazole (XI). Debenzylation of compound (XI) with conc. HCl in refluxing ethanol gives the carbinol (XII), which is finally treated with trichloroacetyl isocyanate and triethylamine in methanol/water.

Cyclization of 2,2-dichloroisobutyraldehyde (I) - obtained by reaction of isovaleraldehyde (II) with chlorine in DMF - with 2-benzyloxyacetaldehyde (III) - produced by reaction of 2-butene-1,4-diol (IV) with benzyl chloride by means of NaOH in water, followed by ozonolysis in MeOH and finally reduction with triphenylphosphine in ethyl acetate - and aqueous NH4OH in methanol gives the imidazole derivative (VI), which is iodinated with I2 and NaOH in dichloromethane to yield the 5-iodoimidaz-ole derivative (VII). Condensation of compound (VII) with bis(3,5-dichlorophenyl)disulfide (VIII) by means of LiH in DMSO affords the dichlorophenylsulfanyl imidazole (IX), which is alkylated with 4-(chloromethyl)pyridine (X) and K2CO3 in DMF to provide the fully substituted imidazole (XI). Debenzylation of compound (XI) with conc. HCl in refluxing ethanol gives the carbinol (XII), which is finally treated with trichloroacetyl isocyanate and triethylamine in methanol/water.

The debenzylation of 2-(benzyloxymethyl)-5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1H-imidazole (IX) with hot aqueous HCl gives 5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1H-imidazole-2-methanol (XIII), which is condensed with chlorosulfonyl isocyanate in acetonitrile to yield carbamic acid 5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1H-imidazol-2-ylmethyl ester (XIV). Finally, this compound is alkylated with 4-(chloromethyl)pyridine (X) - obtained by reaction of 4-(hydroxymethyl)pyridine (XV) and SOCl2 in acetonitrile - by means of NaHCO3 in ethyl acetate/water.

Alkylation of 2-(benzyloxymethyl)-4-isopropyl-1H-imidazole (VI) with 4-(chloromethyl)pyridine (X) by means of NaOH in toluene gives 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI), which is then condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) - obtained by reaction of bis(3,5-dichlorophenyl)-disulfide (VIII) first with chlorine gas in CCl4 or toluene and then dried nitrogen gas - by means of triethylamine in toluene/water to afford 2-(benzyloxymethyl)-5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XI). Debenzylation of compound (XI) by means of hot aqueous HCl provides the hydroxymethyl derivative (XII), which is finally esterified with chlorosulfonyl isocyanate in ethyl acetate.

Debenzylation of 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI) with hot aqueous HCl gives the hydroxymethyl derivative (XVIII), which is condensed with chlorosulfonyl isocyanate in ethyl acetate to yield carbamic acid 1-(4-pyridylmethyl)-4-isopropyl-1H-imidazol-2-ylmethyl ester (XIX). Finally, this compound is condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) by means of triethylamine in DMF/toluene.

Esterification of 4-isopropyl-1-(4-pyridylmethyl)-1H-imidazol-2-ylmethanol (XVIII) by means of acetyl chloride and triethylamine in dichloromethane gives the acetate ester (XX), which is condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) by means of triethylamine in toluene/acetonitrile to yield the thioether (XXI). Hydrolysis of the acetate group of compound (XXI) by means of NaOH in ethanol affords the hydroxymethyl compound (XII), which is finally condensed with chlorosulfonyl isocyanate in acetonitrile.

Cyclization of 2,2-dichloroisobutyraldehyde (I) - obtained by reaction of isovaleraldehyde (II) with chlorine in DMF - with 2-benzyloxyacetaldehyde (III) - produced by reaction of 2-butene-1,4-diol (IV) with benzyl chloride by means of NaOH in water, followed by ozonolysis in MeOH and finally reduction with triphenylphosphine in ethyl acetate - and aqueous NH4OH in methanol gives the imidazole derivative (VI), which is iodinated with I2 and NaOH in dichloromethane to yield the 5-iodoimidaz-ole derivative (VII). Condensation of compound (VII) with bis(3,5-dichlorophenyl)disulfide (VIII) by means of LiH in DMSO affords the dichlorophenylsulfanyl imidazole (IX), which is alkylated with 4-(chloromethyl)pyridine (X) and K2CO3 in DMF to provide the fully substituted imidazole (XI). Debenzylation of compound (XI) with conc. HCl in refluxing ethanol gives the carbinol (XII), which is finally treated with trichloroacetyl isocyanate and triethylamine in methanol/water.

Cyclization of 2,2-dichloroisobutyraldehyde (I) - obtained by reaction of isovaleraldehyde (II) with chlorine in DMF - with 2-benzyloxyacetaldehyde (III) - produced by reaction of 2-butene-1,4-diol (IV) with benzyl chloride by means of NaOH in water, followed by ozonolysis in MeOH and finally reduction with triphenylphosphine in ethyl acetate - and aqueous NH4OH in methanol gives the imidazole derivative (VI), which is iodinated with I2 and NaOH in dichloromethane to yield the 5-iodoimidaz-ole derivative (VII). Condensation of compound (VII) with bis(3,5-dichlorophenyl)disulfide (VIII) by means of LiH in DMSO affords the dichlorophenylsulfanyl imidazole (IX), which is alkylated with 4-(chloromethyl)pyridine (X) and K2CO3 in DMF to provide the fully substituted imidazole (XI). Debenzylation of compound (XI) with conc. HCl in refluxing ethanol gives the carbinol (XII), which is finally treated with trichloroacetyl isocyanate and triethylamine in methanol/water.

The debenzylation of 2-(benzyloxymethyl)-5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1H-imidazole (IX) with hot aqueous HCl gives 5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1H-imidazole-2-methanol (XIII), which is condensed with chlorosulfonyl isocyanate in acetonitrile to yield carbamic acid 5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1H-imidazol-2-ylmethyl ester (XIV). Finally, this compound is alkylated with 4-(chloromethyl)pyridine (X) - obtained by reaction of 4-(hydroxymethyl)pyridine (XV) and SOCl2 in acetonitrile - by means of NaHCO3 in ethyl acetate/water.

Alkylation of 2-(benzyloxymethyl)-4-isopropyl-1H-imidazole (VI) with 4-(chloromethyl)pyridine (X) by means of NaOH in toluene gives 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI), which is then condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) - obtained by reaction of bis(3,5-dichlorophenyl)-disulfide (VIII) first with chlorine gas in CCl4 or toluene and then dried nitrogen gas - by means of triethylamine in toluene/water to afford 2-(benzyloxymethyl)-5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XI). Debenzylation of compound (XI) by means of hot aqueous HCl provides the hydroxymethyl derivative (XII), which is finally esterified with chlorosulfonyl isocyanate in ethyl acetate.

Debenzylation of 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI) with hot aqueous HCl gives the hydroxymethyl derivative (XVIII), which is condensed with chlorosulfonyl isocyanate in ethyl acetate to yield carbamic acid 1-(4-pyridylmethyl)-4-isopropyl-1H-imidazol-2-ylmethyl ester (XIX). Finally, this compound is condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) by means of triethylamine in DMF/toluene.

Esterification of 4-isopropyl-1-(4-pyridylmethyl)-1H-imidazol-2-ylmethanol (XVIII) by means of acetyl chloride and triethylamine in dichloromethane gives the acetate ester (XX), which is condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) by means of triethylamine in toluene/acetonitrile to yield the thioether (XXI). Hydrolysis of the acetate group of compound (XXI) by means of NaOH in ethanol affords the hydroxymethyl compound (XII), which is finally condensed with chlorosulfonyl isocyanate in acetonitrile.