ITMI20061949A1 - PROCEDURE FOR THE SYNTHESIS OF PYRIDINE COMPOUNDS - Google Patents

Description

Description of the patent for industrial invention entitled:

"PROCEDURE FOR THE SYNTHESIS OF PYRIDINE COMPOUNDS"

FIELD OF THE INVENTION

The present invention relates to a new method for obtaining pyridine compounds useful in therapy, in particular in the treatment of pathologies associated with an increase in gastric secretion.

STATE OF THE TECHNIQUE

Sulfinyl compounds, which act as proton pump inhibitors, are used in the treatment of pathologies associated with increased gastric secretion. Examples of these compounds, known as "prazoles", are omeprazole, esomeprazole, pantoprazole, rabeprazole, lansoprazole, tenatoprazole and hydroxymprazole.

The synthesis of these products is basically carried out following the scheme shown here, where R1-R7 and Q are for example as defined here

It is evident that their synthesis requires numerous and laborious steps. Furthermore, a key step of the known processes is the oxidation of a thioether intermediate (-S-) to give the corresponding sulfinyl derivative (-SO-). Hydrogen peroxide and sodium hypochlorite are normally preferred as oxidizing agents. However, the handling of large quantities of hydrogen peroxide presents considerable risks for the safety of operators. In addition, the oxidation of the thioether intermediate (-S-), due to concomitant processes of over-oxidation, can lead to unwanted sulphonic derivatives (-SO2-) that must be removed. All this leads to lower yields and long processing times. There is therefore a need for an alternative and advantageous method for the synthesis of these compounds.

SUMMARY OF THE INVENTION

A new method has been found here for the preparation of a pyridine compound of formula (I), having the formula reported here, which overcomes the technical problems described above and provides a pyridine derivative of formula (I) or a salt thereof, with a degree of purity equal to or greater than 99.5%.

DETAILED DESCRIPTION OF THE INVENTION

The subject of the invention is a process for the preparation of a compound of formula (I) or a salt thereof, both as a mixture of isomers and as a single isomer,

where is it

Q is = CR8- or = N-;

each of R1, R2, R3 and R4 is independently selected from hydrogen, halogen, hydroxy; nitro; C1-C6 alkyl optionally substituted by hydroxy; C1-C6 alkylthio; C1-C6 alkoxy optionally replaced by halogen or C1-C6 alkoxy; phenyl-C1-C6 alkyl; phenyl-alkoxy C1-C6; and -N (RaRb) where each of Ra and Rb, independently, is hydrogen or C1-C6 alkyl or Ra and Rb, taken together with the nitrogen atom to which they are joined, form a saturated heterocyclic ring; and each of R5, R6, R7 and R8 is independently selected from hydrogen, halogen, hydroxy; C1-C6 alkyl optionally substituted by hydroxy; C1-C6 alkylthio; C1-C6 alkoxy optionally replaced by halogen; C1-C6alkyl-carbonyl, C1-C6alkoxy-carbonyl, and oxazol-2-yl; comprising:

a) the reaction of a compound of formula (II) or a salt thereof,

where R1, R2, R3 and R4 are defined as above, and X is hydrogen or a leaving group; with a compound of formula (III) or a salt thereof

where Q, R5, R6 and R7 are defined as above; in the presence of a basic agent; optionally in the presence of a catalyst and / or by heating, if necessary in an organic solvent; or

b) the conversion of a compound of formula (IV) or a salt thereof,

where Q, R1, R2, R3, R4, R5, R6 and R7 are as defined above, or a salt thereof, optionally in the presence of a catalyst and / or by heating, if necessary in an organic solvent and, if desired, the conversion of a compound of formula (I) in one of its salt or in another compound of formula (I); and / or, if desired, the resolution of a mixture thereof of isomers of a compound of formula (I) in the individual isomers.

A compound of formula (IV) can also be represented thus

where Q and R1-R7 are as defined above.

A salt of a compound of formula (I), (II), (III) or (IV) is preferably a salt with an acid or a base, preferably pharmaceutically acceptable.

An isomer of a compound of formula (I) can be, for example, a geometric or optical isomer thereof, preferably an (R) or (S) enantiomer.

An alkyl group in one of the substituents R1-R8, defined above, can be linear or branched, preferably a C1-C4 alkyl group, in particular methyl, ethyl, propyl, isopropyl, butyl or tert.butyl, more preferably methyl, ethyl or propyl.

A halogen is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

A C1-C6 alkyl group substituted by hydroxy is preferably a C1-C4 alkyl group substituted by one or two hydroxy groups, in particular -CH2OH.

A C1-C6 alkoxy group substituted by halogen is preferably a C1-C4 alkoxy group substituted by one, two or three halogen atoms, more preferably two or three fluorine atoms, in particular -OCHF2 or -OCH2CF3.

A C1-C6 alkoxy group substituted by C1-C6 alkoxy is preferably a C1-C4 alkoxy group substituted by C1-C4 alkoxy, in particular C1-C3-OCH3 alkoxy.

A -N group (RaRb) is preferably an amino, methylamino, ethylamino, propylamino, dimethylamino group. When Ra and Rb, taken together with the nitrogen atom to which they are joined, form a saturated heterocyclic ring, this can be a pent- or hexatomic heterocycle optionally containing an additional nitrogen or oxygen atom. Examples of such a group are pyrrolidine, piperidino, piperazino and morpholino.

In particular, a compound of formula (I), as defined above, is preferred, where:

Q is = CH- or = N-; R 2 is hydrogen, or C1-C4 alkyl optionally substituted by hydroxy;

R3 is C1-C4 alkoxy optionally replaced by C1-C4 alkoxy or halogen;

R4 is C1-C4 alkyl or C1-C4 alkoxy;

R6 is hydrogen, C1-C4 alkoxy optionally replaced by halogen; R7 is hydrogen or C1-C4 alkoxy;

R1 and R5 are hydrogen; or one of its salt.

Specific examples of compounds of formula (I) are:

• 2- (3,4-dimethoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole (Pantoprazole);

• 2- (4-chloro-3-methoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole;

• 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole (omeprazole);

• 5-methoxy-2 - {[(4-methoxy-3-methyl-5-hydroxymethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole (hydroxyomeprazole);

• 2 - {[3-methyl-4- (2,2,2-trifluoroethoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole (lansoprazole);

• 2 - {[3-methyl-4- (3-methoxy-propoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole (rabeprazole); And

• 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-imidazo [4,5-b] pyridine (tenatoprazole);

and their salts.

In a compound of formula (II) a leaving group X can be for example a halogen atom, preferably chlorine or bromine, in particular bromine, or a hydroxyl group activated by esterification, for example through an alkanesulfonyl group, typically mesyl, or a arylsulfonyl group, typically tosyl, or a perfluoroalkanesulfonyl group, for example trifluoromethanesulfonyl and nonafluorobuthanesulfonyl.

A basic agent is, for example, a hydroxide or a carbonate of an alkali or alkaline earth metal, preferably lithium, sodium, potassium or calcium; in particular sodium, potassium, lithium or calcium hydroxide; sodium or potassium carbonate; or a tertiary organic amine such as triethylamine or ethyldiisopropylamine.

The reaction between a compound (II) and a compound (III) can be carried out in the presence of a catalyst, for example a catalyst based on a metal or one of its salt, optionally in the presence of a binding agent, or a Lewis acid .

Examples of metal-based catalysts are typically those having affinity for oxygen, e.g. Ti (II), Ti (IV), V (II), V (III), V (V), Cr (II), Cr (III), Mn (III), Mn (IV), Fe (II), Fe (III), Nb (III), Mo (II), Mo (III), Mo (IV), Mo (V), W (II), W (III), W (IV), Tc (III), Re (III), Re (V), Ru (II), Ru (III), Ru (IV), Os (II), Os (III), Os (IV), Os (VI), Pd (II), Hf (IV), Pt (II) or Hg (II) or mixtures of two or more of them, preferably mixtures of two of them, optionally replaced by binders such as halides, hydroxide, alkoxide, carboxylate (eg acetate or tartrate), carbonate, hydrogen carbonate, salts of mineral acids (eg sulphate or phosphate), cyanide, cyanate, thiocyanate, dithiolates such as ethane-1, 2-dithiolate, dialkylthiocarbamates such as diethyl dithiocarbamate, enolates such as acetylacetonate, phosphines (e.g. triphenylphosphine or tricyclohexylphosphine), chiral phosphines such as BINAP (2,2'-Bis (diphenylphosphino) -1,1'-binaphthalene, an carbon monoxide , olefins (ethylene and 1,4-cyclooctadiene), arenes (benzene), carbenes (benzylidene), heterocyclic carbenes (imidazolinidene) phthalocyanines, porphyrines (meso-tetraphenylporphyrin), amines such as triethylamine and piperidine, chelating amines such as ethylenediamine such as 1,4,7,10tetraazacyclododecane, heterocyclic ligands such as 1,10-phenanthroline, 8-hydroxy or 8-mercaptoquinoline or 2,2'-bipyridine, ethylenediamino tetraacetic acid and its salts, nitriloacetic acid and its salts, glyoxymates (dimethylglyxymate) and di-imine type ligands, for example chiral salen ((R, R) -N, N'-Bis (3,5-di-tertbutylsalicylidene) -1,2-cyclohexanediamine), esters and amides of tartaric acid.

Other examples of catalysts are Lewis acids such as for example trimethylsilyl triflate and in general trialkylsilyl halides, trialkyl boranes and trihalides of boron and N-halogen derivatives such as N-chlorosuccinimide, trichloroisocyanuric acid and its salts, for example sodium or potassium, chloramine -T.

An organic solvent can be a protic or aprotic solvent, typically an ether, for example tetrahydrofuran, dioxane, diethyl ether; a chlorinated solvent, for example dichloromethane, dichloroethane, tetrachlorethylene, chlorobenzene or dichlorobenzene, a C1-C6 alkanol, for example methanol, ethanol or isopropanol; an aliphatic or aromatic hydrocarbon, for example toluene; or a frequently ester, for example ethyl acetate or butyl acetate; a dipolar aprotic solvent, for example acetonitrile, dimethylformamide, dimethylacetamide or dimethyl sulfoxide; or a mixture of two to four of such solvents, in particular of 2 or 3 solvents.

An excess of basic agent, as defined above, can be used as a solvent.

The reaction between a compound (II) and a compound (III) or their salts, can be carried out in the presence or absence of catalyst at a temperature between approximately -10 ° C and the reflux temperature of the solvent or of the reaction mixture . Preferably, when in the absence of catalyst, at a temperature comprised approximately between 100 ° C and the reflux temperature of the solvent or of the reaction mixture; when in the presence of catalyst, at a temperature between about -10 ° C and the reflux temperature of the solvent or of the reaction mixture.

The stoichiometric ratio between a compound (II) and a compound (III) or their salts can be comprised approximately between 0.5 and 2, preferably between about 0.8 and 1.2.

The catalyst can be in an amount between 0.5 and 20%, preferably between 1 and 10%, with respect to the amount of compound (II).

The conversion of a compound (IV) or its salt into a compound (I) or its salt, can be carried out in the presence of a catalyst, if necessary in an organic solvent, at a temperature between approximately -10 ° C and the reflux temperature of the solvent or reaction mixture; or in the absence of catalyst, in an organic solvent, at a temperature between approximately 100 ° C and the reflux temperature of the solvent or of the reaction mixture; or in the absence of catalyst and solvent at the melting temperature of the compound (IV) or its salt.

A catalyst can be for example a catalyst based on a metal or a salt thereof, or mixtures of two or more of them, preferably mixtures of two of them, optionally in the presence of a binding agent, as reported above; or a Lewis acid as exemplified above.

Typically the catalyst is present in quantities ranging from 0.5 to 20%, preferably between 1 and 10%, with respect to the amount of compound (IV).

Before being converted into a compound (I), a compound (IV) or a salt thereof can be converted according to known methods into another compound (IV) or a salt thereof, even without being isolated from the reaction mixture.

An organic solvent can be a protic or aprotic solvent. Typically an ether, or a mixture of two to four solvents, as previously reported.

The optional conversion of a compound (I) into another compound (I) or into a salt thereof, as well as the resolution of a mixture of isomers of a compound (I) into the single isomers can be carried out by known methods.

The compounds of formula (II) and (III) and their salts are known and can be prepared according to known methods, some are commercially available. A compound (IV) or a salt thereof can be obtained for example by reaction between a compound (II) in which X is a leaving group and a compound (III) or their salts, in the presence of a base and at room temperature, such as reported in ES 2063705. It should be noted that according to ES 2063705 a compound (IV) can be converted into lansoprazole by reduction of the N-oxide group and subsequent oxidation of the thioether intermediate (-S-) to sulfoxide (-SO-) , which however originates concomitant over-oxidation processes that lead to unwanted sulphonic derivatives (-SO2-).

The compounds of formula (IV), and their salts, in which:

R3 is -O (CH2) 3-OCH3, R4 is CH3, R1, R2 and R5-R7 are hydrogen and Q is = CH-; and R3 and R4 are OCH3; R6è -OCHF2, R1, R2, R5e R7 are hydrogen and Q is = CH- are new compounds and constitute a further object of the invention.

The process of the invention provides a pyridine derivative of formula (I) and formula (IV) or a salt thereof, with a degree of purity equal to or greater than 99.5%, typically greater than 99.9%, so as to satisfy the requirements of the regulatory standards. It is therefore evident that a compound of formula (I) or a salt thereof thus obtained is free or substantially free from unwanted sulphonic derivatives (-SO2-).

The following examples illustrate the invention.

EXAMPLE 1

2- (4-chloro-3-methoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole

RuCl3 (63.1 mg, 0.30 mmol), THF (2.0 ml) and 1,4-dioxane (2 , 0 ml). A solution of trisodium ETDA in water (0.13M, 2.37 ml, 0.30 mmol) is then added. A solution of 2- (4-chloro-3-methoxy-1-oxipyridin-2-ylmethylsulfanil) -5-difluoromethoxy-1H-benzimidazole (1.178 g, 3.05 mmol) in 1,4-dioxane (12 ml) while heating to reflux (about 80 ° C). After one hour it is cooled, the solvent is evaporated under vacuum and the desired product is purified by flash chromatography.

<1> H NMR (300 MHz, CDCl3): δ 8.12 (1H, d, J = 5.0 Hz), 7.54 (1H, d, J = 8.7 Hz), 7.33 (1H, s), 7.25 (1H, d, J = 5.0 Hz), 7.08 (1H, dd, J = 8.7, 2.4 Hz), 6.52 (1H, t, J = 74.1 Hz), 4.87 & 4.78 (2x1H, AB system, J = 13.2 Hz), 3.85 (3H , s).

Proceeding in a similar way, starting from the respective 1-oxypyridine derivatives we obtain:

• 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole;

• 5-methoxy-2 - {[(4-methoxy-3-methyl-5-hydroxymethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole;

• 2 - {[3-methyl-4- (2,2,2-trifluoroethoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole;

• 2 - {[3-methyl-4- (3-methoxy-propoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole; And

• 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-imidazo [4,5-b] pyridine.

EXAMPLE 2

2- (3,4-Dimethoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole (Pantoprazole)

RuCl3 (27.0 mg, 0.13 mmol), THF (1.0 ml), H2O (0.05 ml), EDTA trisodium hydrate (46.7 mg, 0.13 mmol) A solution of 2- (3,4-dimethoxy-1-oxipyridin-2-ylmethylsulfanil) -5-difluoromethoxy-1H-benzimidazole (500 , 0 mg, 1.30 mmol) in 1,4-dioxane (6 ml) and heated under reflux (about 80 ° C). After one hour it is cooled, the solvent is evaporated under vacuum and the desired product is purified by flash chromatography.

<1> H NMR (300 MHz, d6-DMSO NaOD) δ 8.23 (1H, d, J = 5.4 Hz), 7.46 (1H. D, J = 8.7 Hz), 7.26 (1H, d, J = 4.8 Hz) , 7.08 (1H, d, J = 5.7 Hz), 7.03 (1H, t, JHF = 84 Hz), 6.74 (1H, dd, J = 5.7, 2.4 Hz), 4.63 & 4.38 (2x1H, system AB, J = 12 Hz), 3.90 (3H, s), 3.78 (3H, s).

EXAMPLE 3

2- (4-chloro-3-methoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole

4-chloro-2-chloromethyl-3-methoxypyridine N-oxide (8.9 g, 43 mmol) 40 ml of THF and then a solution of 5-difluoromethoxy-2-mercapto-1H-benzimidazole (9.3 g, 43 mmol) and triethylamine (13 g, 128 mmol) in 20 ml of THF maintaining the temperature below 40 ° C.

After 3 hours, water (30 ml) is added to obtain a clear solution and 10% HCl is added until pH = 5.

Trisodium EDTA monohydrate (1.54 g, 4.3 mmol) and RuCl3 (0.9 g) are then added. The mixture is heated to 60 ° C under nitrogen for 8 hours, filtered on celite and the solvent evaporated under vacuum. It is extracted with ethyl acetate and the residue is purified by flash chromatography.

Proceeding in the same way we obtain:

• 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole;

• 5-methoxy-2 - {[(4-methoxy-3methyl-5-hydroxymethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole;

• 2 - {[3-methyl-4- (2,2,2-trifluoroethoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole;

• 2 - {[3-methyl-4- (3-methoxy-propoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole; And

• 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-imidazo [4,5-b] pyridine.

EXAMPLE 4

2- (4-Chloro-3-methoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole

10 g of 5-difluoromethoxy-2-mercapto-1H-benzimidazole (46.3 mmol) are loaded into a 250 ml 4-neck flask, equipped with a mechanical stirrer, thermometer, reflux refrigerant and nitrogen valve, 8 g of 4-chloro-2-methyl-3-methoxypyridine-N-oxide (46.3 mmol), 50 ml of tetrahydrofuran and 50 ml of chloroform. The system is cooled to a temperature between 0 and 5 ° C and 6.2 g of N-chlorosuccinimide (46.3 mmoles) are added. During the addition, the formation of a yellow suspension is observed. 14 g of triethylamine (138.8 mmoles) are added and the system is allowed to spontaneously return to room temperature. Subsequently the system is brought to reflux (62 ° C) and it is allowed to reflux for 48 h.

HPLC-MS analysis shows the formation of 2- (4-chloro-3-methoxypyridin-2-yl) -metansulfinyl-5-difluoromethoxy-1H-benzimidazole.

Claims (22)

CLAIMS 1. Process for the preparation of a compound of formula (I) or a salt thereof, either as a mixture of isomers or as a single isomer, where is it Q is = CR8- or = N-; each of R1, R2, R3 and R4 is independently selected from hydrogen, halogen, hydroxy; nitro; C1-C6 alkyl optionally substituted by hydroxy; C1-C6 alkylthio; C1-C6 alkoxy optionally replaced by halogen or C1-C6 alkoxy; phenyl-C1-C6 alkyl; phenyl-alkoxy C1-C6; and -N (RaRb) where each of Ra and Rb, independently, is hydrogen or C1-C6 alkyl or Ra and Rb, taken together with the nitrogen atom to which they are joined, form a saturated heterocyclic ring; and each of R5, R6, R7 and R8 is independently selected from hydrogen, halogen, hydroxy; C1-C6 alkyl optionally substituted by hydroxy; C1-C6 alkylthio; C1-C6 alkoxy optionally replaced by halogen; C1-C6alkyl-carbonyl, C1-C6alkoxy-carbonyl, and oxazol-2-yl; comprising: a) the reaction of a compound of formula (II), or a salt thereof, where R1, R2, R3 and R4 are defined as above, and X is hydrogen or a leaving group; with a compound of formula (III) or a salt thereof where Q, R5, R6 and R7 are defined as above; in the presence of a basic agent; optionally in the presence of a catalyst and / or by heating, if necessary in an organic solvent; or b) the conversion of a compound of formula (IV), or a salt thereof, where Q, R1, R2, R3, R4, R5, R6 and R7 are defined as above, in said compound of formula (I), or a salt thereof, optionally in the presence of a catalyst and / or by heating, if necessary in a solvent organic; and, if desired, the conversion of a compound of formula (I) into a salt thereof or into another compound of formula (I); and / or, if desired, the resolution of a mixture thereof of isomers of a compound of formula (I) in the individual isomers. 2. Process according to claim 1, variant a), where the basic agent is a hydroxide or a carbonate of an alkaline or alkaline-earth metal, or a tertiary organic amine. 3. Process according to claim 2, where the basic agent is selected from sodium, potassium, lithium or calcium hydroxide; sodium or potassium carbonate; triethylamine and ethyldiisopropylamine. 4. Process according to claim 1, wherein a leaving group X is a halogen atom or a hydroxyl group activated by esterification. 5. Process according to claim 1, where the reaction between a compound of formula (II), or a salt thereof, and a compound of formula (III), or a salt thereof, is carried out in the absence of catalyst at a temperature comprised approximately between 100 ° C and the reflux temperature of the solvent or reaction mixture. 6. Process according to claim 1, where the reaction between a compound of formula (II), or a salt thereof, and a compound of formula (III), or a salt thereof, is carried out in the presence of catalyst at a temperature comprised approximately between -10 ° C and the reflux temperature of the solvent or reaction mixture. 7. Process according to each of claims 1, 5 and 6 where the solvent is an excess of basic agent, as defined in claim 2. 8. Process according to each of claims 1 to 7, wherein the stoichiometric ratio between a compound of formula (II) or a salt thereof, and a compound of formula (III), or a salt thereof is comprised approximately between 0.5 and 2. 9. Process according to claim 8, wherein said stoichiometric ratio is comprised between about 0.8 and 1.2. 10. Process according to claim 1, where the conversion of a compound of formula (IV) or a salt thereof, into a compound of formula (I) or a salt thereof is carried out in the presence of a catalyst, if necessary in an organic solvent , at a temperature between approximately -10 ° C and the reflux temperature of the solvent or reaction mixture. 11. Process according to claim 1, wherein the conversion of a compound of formula (IV) or a salt thereof, into a compound of formula (I) or a salt thereof is carried out in the absence of catalyst, in an organic solvent, to a temperature between approximately 100 ° C and the reflux temperature of the solvent or reaction mixture. 12. Process according to claim 1, where the conversion of a compound of formula (IV) or a salt thereof, into a compound of formula (I) or a salt thereof is carried out in the absence of catalyst and solvent at the melting temperature of the composed of formula (IV) or its salt. 13. Process according to each of claims 1, 6 and 10 where the catalyst is a catalyst based on a metal, or a salt thereof, having an affinity for oxygen or a Lewis acid. 14. Process according to claim 13, where the catalyst is based on a metal selected from Ti (II), Ti (IV), V (II), V (III), V (V), Cr (II), Cr (III), Mn (III), Mn (IV), Fe (II), Fe (III), Nb (III), Mo (II), Mo (III), Mo (IV), Mo (V), W (II), W (III), W (IV), Tc (III), Re (III), Re (V), Ru (II), Ru (III), Ru (IV), Os (II), Os (III), Os (IV), Os (VI), Pd (II), Hf (IV), Pt (II) and Hg (II) or mixtures of two or more of them, optionally replaced by binders. 15. Process according to claim 13 where Lewis acid is selected from trimethylsilyl triflate, N-chlorosuccinimide, trichloroisocyanuric acid and its salts and chloramine-T. 16. Process according to each of claims 1, 6, 10, 13, 14 and 15, where the amount of catalyst is between 0.5 and 20% with respect to the amount of compound of formula (II) or of formula (IV ). 17. Process according to claim 16, where the amount of catalyst is between 1 and 10%. 18. Process according to each of claims 1, 5, 6, 10 and 11 where the organic solvent is selected from an ether, a chlorinated solvent, a C1-C6 alkanol; an aliphatic or aromatic hydrocarbon, an ester solvent, a dipolar aprotic solvent, or a mixture of two to four such solvents. 19. Process according to claim 18, where the solvent is selected for example tetrahydrofuran, dioxane, diethyl ether, dichloromethane, dichloroethane, tetrachlorethylene, chlorobenzene, dichlorobenzene, methanol, ethanol, isopropanol, toluene, ethyl acetate, butyl acetate, dimethylacetamide, acetylacetamide and dimethylacetamide, dimethyl sulfoxide. 20. Process according to each of the preceding claims, where in the compound of formula (I) Q is = CH- or = N-; R 2 is hydrogen or C1-C4 alkyl optionally substituted by hydroxy; R3 is C1-C4 alkoxy optionally replaced by C1-C4 alkoxy or halogen; R4 is C1-C4 alkyl or C1-C4 alkoxy; R6 is hydrogen, C1-C4 alkoxy optionally replaced by halogen; R7 is hydrogen or C1-C4 alkoxy; R1 and R5 are hydrogen. 21. Process according to each of the preceding claims, where the compound of formula (I) is selected from: • 2- (3,4-dimethoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H-benzimidazole; • 2- (4-chloro-3-methoxypyrid-2-yl) methanesulfinyl-5-difluoromethoxy-1H benzimidazole; • 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole; • 5-methoxy-2 - {[(4-methoxy-3methyl-5-hydroxymethyl-2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole; • 2 - {[3-methyl-4- (2,2,2-trifluoroethoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole; • 2 - {[3-methyl-4- (3-methoxy-propoxy) -2-pyridinyl) methyl] sulfinyl} -1H-benzimidazole (rabeprazole); And • 5-methoxy-2 - {[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl} -1H-imidazo [4,5-b] pyridine; or one of its salt. 22. A compound of formula (IV), or a salt thereof, as defined in claim 1, wherein: R3 is -O- (CH2) 3-OCH3, R4 is CH3, Q is = CH-; and R1, R2 and R5-R7 are hydrogen; or R3 and R4 are OCH3; R6 is -OCHF2, and Q is = CH-; and R1, R2, R5 and R7 are hydrogen.