Patent GB-1167976-A (GB)
Title: Heterocyclylmethyl Alkyl Sufones
Inventor: SHEN TSUNG-YING
IPC: C07D333/28
Filed: 1967-11-06
Abstract: 1,167,976. Methyl sulphonyl methyl-heterocyclic compounds. MERCK & CO. Inc. 6 Nov., 1967 [9 Nov., 1966], No. 50358/67. Heading C2C. The invention comprises compounds of the general Formula I in which " Het " is a hetero-aromatic radical containing one or two 5- or 6-membered rings and that contains more than one hetero atom if it is a monocyclic oxa or thia radical and if R 2  and R 3  are both hydrogen, Y is a hydrogen or halogen atom or a C 1-5  alkyl, C 2-5  alkenyl, C 3-6  cyclo-alkyl, amine, C 1-5  alkylamino, di-(C 1-5  alkyl)-amino, C i - 5  alkoxy, hydroxy, mercapto, nitro, C i - 5  alkanoyl or C 1-5  alkylmercapto; n is 0, 1 or 2; each of R 2  and R 3  is a hydrogen atom or a C 1-5  alkyl or C 2-5  alkenyl radical, and R 4  is a C 1-5  alkyl or C 2-5  alkenyl radical, which are prepared by reacting a compound of the formula (Y) n -Het-CH 2 -X where X is a chlorine, bromine or iodine atom with an alkali metal R 4 - sulphinate to produce a compound of Formula I wherein R 2  and R 3  both are hydrogen atoms. When " Het " is indole, compounds of Formula I are prepared by reacting a compound of the formula with dimethylamine and formaldehyde to produce the corresponding 3-dimethylamine methyl derivative and reacting this with an alkali metal R 4 -sulphinate to produce a compound of the formula where R 4  is as defined above and R 5  and R 6  are each equal to a hydrogen atom or Y, defined previously. Compounds of Formula I in which " Het " contains nitrogen and at least one of R 2  and R 3  is other than hydrogen are prepared by reacting a compound of the formula (Y) n -[Het]-CH 2 -R 5 , in which Y and n are as defined above and R 5  is a C 1-5  alkyl or C 2-5  alkenyl radical with an α-halo succinimide in an inert solvent in the presence of at least a catalytic amount of peroxide to form the corresponding α-halo compound and reacting this with an alkali metal R 4 -sulphinate where R 4  is as defined above. Compounds of Formula I in which " Het " contains oxygen and/or sulphur and containing more than one hetero atom if it is monocyclic and at least one of R 2  and R 3  is other than hydrogen are prepared by reacting a compound of the formula (Y) n -[Het]-CH 2 -SO 2 -R 4  with C 1-5  alkyl or C 2-5  alkenyl iodide in the presence of a base. Compounds of Formula I in which " Het " is a heterocyclic residue containing at least one nitrogen atom are prepared by reacting a compound of the formula (Y) n -[Het] with a sulphide of the formula in the presence of an alkali or alkaline earth metal hydride to form a heterocyclic sulphide compound and oxidizing this to give a compound of Formula I, and the sulphone residue is attached to the nitrogen atom. 2- or 4-Chloromethylthiazole is prepared by reacting thionyl chloride with 2- or 4-hydroxymethylthiazole which is prepared by treating thiazole with formalin to give the 2-hydroxy compound and by reducing 4-formylthiazole with sodium borohydride to give the 4-hydroxythiazole. 3 - Chloromethylpyrazole (or 4 - chloromethylimidazole is prepared by reacting thionyl chloride with 3-hydroxymethylpyrazole (or 4-hydroxymethyl imidazole) which is prepared by reducing 3 - ethoxycarbonylpyrazole (or 4-ethoxycarbonylimidazole) with lithium aluminium hydride. The esters are prepared by treating 3-carbozypyrazole or 4-carboxy imidazole with ethanol. 3-Carboxy-pyrazole is prepared by treating 3 - methylpyrazole with potassium permanganate. i-Carboxy-imidazole is prepared by the acid hydrolysis of 4-anilinocarbonylimidazole which is prepared by reacting aniline with 4,5-dicarboxyimidazole which is obtained by hydrolysis of the corresponding 4,5-diethyl ester. 2 - Iodomethyl - 1,4 - benzodioxane is prepared by reacting 2-chloromethyl- 1 ,4-benzodioxane with sodium iodide. 2 - Methyl - 3 - dimethylaminomethyl - 5 - methoxyindole is prepared by reacting 2-methyl-5- methoxy indole with formalin and dimethylamine. Pharmaceutical compositions containing as active ingredients compounds of Formula I are administered orally and have anti-inflammatory antipyretic and analgesic activity.