US 6,723,852 B2Granted

Method for obtaining derivatives of [[(pyridil substituted)methyl]thio]benzomidazol

AssigneeEsteve Quimica, S.A.

InventorRamon Berenguer Maimo

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Abstract

The method for obtaining derivatives of [[(pyridil substituted)methyl]thio]benzomidazol (I), where each of R1, R3 and R4, independently of each other, is hydrogen, an alkyl, alkoxy or fluorinated alkoxy of 1 to 6 carbon atoms, and R2 is nitro, halogen, alkoxy or halogenated alkoxy of 1 to 6 carbon atoms, or a group —OR—(CH2)n—OR8, where n is an integer between 1 and 6 and R8 represents hydrogen or an alkyl group with 1 to 6 carbon atoms, which involves (a) reacting an N-oxide of a methylpyridine with an anhydride of activated carboxylic acid or of sulfonic acid, and (b) reacting the intermediate formed in stage (a) with a corresponding mercaptobenzomidazol. The compounds (I) are useful in the synthesis of derivatives of [[(pyridil substituted)methyl]sulfinyl]benzomidazol, such as omeprazol, lansoprazol, rabeprazol or pantoprazol.

Claims22

Dependent claims

A method for obtaining derivatives of [[(pyridil substituted)methyl]thio]benzimidazole having formula (I)

wherein,
each of R1, R3 and R4, independently of each other, is selected from the group consisting of a hydrogen, an alkyl group with 1 to 6 carbon atoms, an alkoxy group with 1 to 6 carbon atoms, and a fluorinated alkoxy group with 1 to 6 carbon atoms;
and R2 is selected from the group consisting of a nitro group, a halogen, an alkoxy group with 1 to 6 carbon atoms, a halogenated alkoxy group with 1 to 6 carbon atoms, and —O—(CH2)n—OR8, wherein n is an integer from 1 to 6, and R8 represents hydrogen or an alkyl group with 1 to 6 carbon atoms,
said method comprising:
a) reacting an N-oxide of methylpyridine with a compound having formula (IV)
wherein R1, R2 and R3 are as described previously with:
(i) an anhydride of an activated carboxylic acid having formula (R6CO)2O, wherein R6 is a halogenated alkyl group;
or
(ii) an anhydride of sulfonic acid having formula (R7SO2)2O, wherein R7 is selected from the group consisting of an alkyl group, a halogenated alkyl group, and an aryl group optionally substituted with an alkyl group,
said reaction being carried out in an organic solvent to provide an intermediate with formula (V) or its corresponding salt
wherein R1, R2 and R3 are as described previously;
and R5 is OCOR6 or OSO2R7 wherein R6 and R7 are as described previously;
and
b) reacting said intermediate having formula (V) with a derivative of 2-mercaptobenzimidazole having formula (III)
wherein R4 is as defined above, in the presence of a base, in an organic solvent, to provide the compound with formula (I).

12 more elements

Dependencies are inferred from the claim text.