MX2007009829A - Benzimidazole compound. - Google Patents

Abstract

A novel compound which is useful as a therapeutic or preventive agent for diseases attributable to gastric hydrochloric acid. It has excellent gastric hydrochloric acid secretion inhibitory activity and is richer in the retention of gastric hydrochloric acid secretion inhibitory activity. It can keep the gastric pH high for long. It is safer and has moderate physicochemical stability. It is a compound represented by the general formula (1) (wherein R¹ and R³ are the same or different and each represents hydrogen or C_1-6 alkyl; R² represents (5,5-dimethyl-1,3-dioxan-2-yl)methoxy, 5,7-dioxaspiro[2.5]oct-6-ylmethoxy, 1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy, (2,2-dimethyl-1,3-dioxan-5-yl)methoxy, etc.; R⁴, R⁵, R⁶, and R⁷ each represents hydrogen, halogeno, C_1-6 alkyl, C_1-6 haloalkyl, C_1-6 alkoxy, C_1-6 haloalkoxy, etc.; and W¹ represents a single bond, methylene, or ethylene), a salt thereof, or a solvate of either.

Description

COMPOSITE OF BENZYMIDAZOL FIELD OF THE INVENTION The present invention relates to a benzimidazole compound or a salt thereof, or a solvate thereof, useful as an inhibitor for the secretion of gastric acid. The present invention also relates to a benzimidazole compound or a salt thereof, or a solvate thereof, useful as a therapeutic agent or prophylactic agent for diseases or symptoms related to acid (especially gastroesophageal reflux diseases, gastroesophageal reflux diseases symptomatic , gastric ulcers and duodenal ulcers). BACKGROUND OF THE INVENTION Peptic ulcers such as gastric ulcer and duodenal ulcer are caused mainly by disruption of balance between aggressive factors, such as acid and pepsin, and the defense factors, such as mucus and blood flow. , which lead to self-digestion. Peptic ulcer is mainly treated through medical care, in such a way that several drug therapies have been treated as medical care.

Particularly, in recent years, a drug capable of specifically inhibiting H + / K + -ATPase, which is an enzyme present in parietal cells and responsible for the stage Ref .: 183370 End of gastric acid secretion, therefore suppressing the secretion of gastric acid and inhibiting self-digestion, have been developed and put into clinical use. Examples of such medications include omeprazole, ezomepazole, pantoprazole, lansoprazole, and rabeprazole. These medications have excellent therapeutic effects; however, it is still desired to develop a drug that more persistently inhibits the secretion of gastric acid, safer, and appropriately psychochemically stable. In particular, it is also suggested that the cure rate of gastroesophageal reflux disease can be improved by keeping the intragastric pH at a high value for a long time (Non-Patent Document 1). The compounds particularly relevant to the present invention are described in the Patent 1 and 2. However, the compounds described in these patent documents differ in chemical structure from the compounds specifically described in the present invention. Patent Document 1: WO 91/19712 Patent Document 2: JP-A-59-181277 Non-Patent Document 1: Digestion 1992; 51 (suppl 1): 59-67 BRIEF DESCRIPTION OF THE INVENTION Problem to be Resolved by the Invention An object of the present invention is to provide a novel compound having an excellent inhibitory effect against the secretion of gastric acid, useful as a therapeutic or prophylactic agent for acid-related diseases or symptoms and being excellent in the maintenance of the inhibitory effect against the secretion of gastric acid, therefore keeping the intragastric pH high for a long time. Means for Solving the Problem The present inventors have conducted intensive studies with the vision toward obtaining the aforementioned objects. As a result, they found that a benzimidazole compound having a new chemical structure has an excellent inhibitory effect against the secretion of gastric acid, it is excellent at maintaining the inhibitory effect against the secretion of gastric acid, thus maintaining the intragastric pH at a high value for a long time, and particularly useful as a therapeutic or prophylactic agent for gastroesophageal reflux disease, symptomatic gastroesophageal reflux disease, gastric ulcer and duodenal ulcer. Based on these findings, the present invention has been achieved. More particularly, the present invention provides a compound having the following formula (1) or a salt thereof, or a solvate thereof.

In addition, the present invention provides a medicament containing a compound having the formula (1) above or a salt thereof, or solvate of these. The present invention also provides a gastric acid secretion inhibitor containing a compound having the formula (1) above or a salt thereof, or a solvate thereof. The present invention further provides a pharmaceutical composition containing a compound having the formula (1) above or a salt thereof, or a solvate thereof or the use of a compound having the above formula (1) or a salt thereof , or a solvate thereof to produce a pharmaceutical composition. Additionally, the present invention is directed to a therapeutic agent or prophylactic agent for diseases or symptoms related to acid, such as gastric ulcer, duodenal ulcer, anastomotic ulcer, gastroesophageal reflux disease (including disease). of gastroesophageal reflux with relapses and repeated recurrences), Zollinger-Ellison syndrome, symptomatic gastroesophageal reflux disease, endoscopically negative gastroesophageal reflux disease, non-erosive gastroesophageal reflux disease, gastroesophageal regurgitation, NUD (non-ulcer dyspepsia), abnormal sensation in the throat, Barrett's esophagus, ulcer induced by? SAID, gastritis, gastric bleeding, hemorrhagic gastritis, gastrointestinal bleeding, peptic ulcer, bleeding ulcer, tension ulcer, gastric hyperacidity, dyspepsia, gastroparesis, ulcer of elderly person, intractable ulcer , acute gastric mucosal lesion, heartburn, heartburn of sleep apnea syndrome, bruxism, gastralgia, heavy stomach sensation, vomiting, nausea, temporomandibular joint arthrosis, or erosive gastritis, and which contain a compound that has a general formula (1) above or a salt thereof, or a s olvato of these. Preferred examples of diseases and symptoms related to the acid may include gastric ulcer, duodenal ulcer, anastotomic ulcer, gastroesophageal reflux disease, Zollinger-Ellison syndrome, symptomatic gastroesophageal reflux disease, endoscopically negative gastroesophageal reflux disease, gastroesophageal reflux disease non-erosive, and gastric mucosal lesion acute More preferred examples may include gastroesophageal reflux disease, symptomatic gastroesophageal reflux disease, gastric ulcer and duodenal ulcer. Other more preferred examples may include (1) gastroesophageal reflux disease or symptomatic gastroesophageal reflux disease and (2) gastric ulcer, or duodenal ulcer. On the other hand, the present invention is directed to a bactericidal agent or an antibacterial agent against Helicobacter pylori, which contains a compound having the formula (1) above or a salt thereof, or a solvate thereof. Note that the "prophylactic agent" mentioned above includes, other than the prophylactic agent that is administered before the onset of a disease or symptom, a maintenance of the therapeutic agent and a recurrence of the preventive agent after the cure. In addition, the "auxiliary bactericidal agent" mentioned above refers to an agent that controls the work of the environment in a bactericidal agent difficult to work under acidic conditions in order to produce the effect. In the formula (1), R1 and R3 may be the same or different and represent a hydrogen atom, or an alkyl group of Cl to C6; and R2 is represented by [formula 2], which may have from 1 to 4 groups selected from the group To the next one. Formula 2 The group Al is the group consisting of a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, a C1-C6 alkoxy-C1-6 alkyl group, C6, and a hydroxyl group. R4 R5, Rd and R7 may be the same or different and each represents a hydrogen atom, a group hydroxyl, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkoxy group, or a combination of R5 and R? they represent a methylenedioxy or ethylenedioxy group, and W1 represents a straight or branched chain alkylene group of individual bond or Cl to C8. W2 represents a hydrogen atom, a C1-C6 alkyl group, or halogen atom (provided that, the occurrence of W2 in the benzene ring may be from 1 to 3, and may be the same or different); ni represents from 1 to 5, n2 represents from 1 to 4, and n3 represents from 1 to 6. The "C1-C6 alkyl group" used herein refers to a linear or branched alkyl group having from 1 to 6 carbon atoms. carbon, such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, neopentyl group, 1-ethylpropyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, 2-methylpentyl group, 1-methylpentyl group, 3-dimethylbutyl group, 2,2-dimethylbutyl group, group 1, 1- dimethylbutyl, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 1-ethylbutyl group or 2-ethylbutyl group. The "halogen atom" used herein is refers to a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. The "C1-C6 alkoxy group" used herein refers to a straight or branched alkoxy group having from 1 to 6 carbon atoms such as a methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, group isobutoxy, s-butoxy group, t-butoxy group, pentoxy group, isopentoxy group, 2-methylbutoxy group, neopentoxy group, hexyloxy group, 4-methylpentoxy group, 3-methylpentoxy group, 2-methylpentoxy group, 3-dimethylbutoxy group , 2,2-dimethylbutoxy group, group 1, 1-dimethylbutoxy, 1,2-dimethylbutoxy group, 1,3-dimethylbutoxy group or 2,3-dimethylbutoxy group. The "C 1 -C 6 haloalkyl group" used herein refers to a C 1 -C 6 alkyl group having 1 to 5 substituents of halogen atoms as mentioned above, for example, including a monofluoromethyl group, monochloromethyl group, monobromomethyl group, monoiodomethyl group, difluoromethyl group, dichloromethyl group, dibromomethyl group, diiodomethyl group, trifluoromethyl group, trichloromethyl group, tribromomethyl group, triiodomethyl group, 1-fluoromethyl group, 2-fluoroethyl group, 2,2,2-trifluoroethyl group 1 -chloroethyl, 2-chloroethyl group, 2, 2, 2-trichloroethyl group, 1-fluoropropyl group, 2-bromopropyl group, group 1 bromobutyl, 1-chloropentyl group, and 1-fluorohexyl group The "C1-C6 haloalkoxy group" used herein refers to a C1-C6 alkoxy group having 1 to 5 substituents of halogen atoms mentioned above, example including a monofluoromethyloxy, monochloromethyloxy group, monobromomethyloxy group, monoiodomyloxy group, difluoromethyloxy group, dichloromethyloxy group, dibromomethyloxy group, diiodomomethyloxy group, trifluoromethyloxy group, trichloromethyloxy group, tribromomethyloxy group, triiodomethyloxy group, 1-fluoroethyloxy group, 2-fluoroethyloxy, 2, 2 , 2-trifluoroethyloxy, 1-chloroethyloxy group, 2-chloroethyloxy group, 2, 2, 2-trichloroethyloxy, 1-fluoropropyloxy group, 2-bromopropyloxy group, 1-bromobutyloxy group, 1-chloropentyloxy bromo, and 1-fluorohexyloxy group. The "Cl-C6 alkoxy group C 1 -C 6 alkyl" as used herein refers to a C 1 -C 6 alkyl group having a single substituent of the aforementioned C 1 -C 6 alkoxy group, for example, including a methoxymethyl group , ethoxymethyl group, propoxymethyl group, 2-methoxyethyl group, 2-ethoxyethyl group, 1-methoxyethyl group, 3-methoxypropyl group, 3-ethoxypropyl group, 4-methoxybutyl group, 4-ethoxybutyl group, 4-propoxybutyl group, 5-methoxypentyl group , 5-ethoxy-pentyl group, 5-propoxypentyl group, 6-methoxyhexyl group, and 6-ethoxyhexyl group.

The "straight or branched chain of C 1 -C 8 alkylene chain" as used herein refers to a methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, propylene (1-methylene), 1-methyltrimethylene, or -methyltrimethylene. The "C1-C6 alkyl group" of R1 mentioned above is preferably a methyl group. The "C 1 -C 6 alkyl group" of R 3 mentioned above is preferably a methyl group. The "halogen atom" of R 4, R 5, R 6 and R 7 mentioned above is preferably a fluorine or chlorine atom and more preferably a fluorine atom. The "C 1 -C 6 alkyl group" of R 4, R 5, R 6 and R 7 mentioned above is preferably a methyl group or ethyl group, and more preferably, a methyl group. The "C 1 -C 6 haloalkyl group" of R 4, R 5, R 6 and R 7 mentioned above is preferably a monofluoromethyl group, difluoromethyl group or trifluoromethyl group, and more preferably a monofluoromethyl group. The "C1-C6 alkoxy group" of R4, R5, R6 and R7 mentioned above is preferably a methoxy or ethoxy group, and more preferably, a methoxy group. The "C1-C6 haloalkoxy group" of R4, R5, R6 and R7 mentioned above is preferably a group monofluoromethyloxy, monochloromethyloxy, difluoromethyloxy group, dichloromethyloxy group, trifluoromethyloxy group or trichloromethyloxy group, and more preferably, a monofluoromethyloxy group or difluoromethyloxy group. The "halogen atom" of the group Al is preferably a fluorine atom. The "C 1 -C 6 alkyl group" of the above-mentioned Al group is preferably a methyl group, ethyl group or propyl group, more preferably a methyl group or ethyl group, and more preferably a methyl group. The "C 1 -C 6 alkoxy group" of the above-mentioned Al group is preferably a methoxy group or an ethoxy group, and more preferably, a methoxy group. The "C1-C6 haloalkyl group" of the above-mentioned Al group is preferably a fluoromethyl group or difluoromethyl group, and more preferably, a fluoromethyl group. The "Cl-C6 alkoxy group of C1-C6 alkyl" of the group Al mentioned above is preferably a methoxymethyl group or ethoxymethyl group. W1 mentioned above is preferably a methylene group or ethylene group, individually linked, and more preferably, a methylene group. The "C1-C6 alkyl group" of W2 mentioned above it is preferably a methyl group. The "halogen atom" of W2 mentioned above is preferably a fluorine atom or chlorine atom, and more preferably, a fluorine atom. The number of substituents present in the benzene ring of W2 mentioned above is preferably 1. W2 mentioned above is preferably a hydrogen atom. not mentioned above is preferably from 1 to 3, and more preferably, 1 or 2. n2 mentioned above is preferably 1 or 2, and more preferably, 1. n3 mentioned above is preferably 1 to 4, and more preferably 1 or 2. In the specification, the structure of a compound sometimes represents a certain isomer for convenience; however, the present invention includes all structurally generated isomers such as geometric isomers, optical isomers, rotational isomers, stereoisomers, tautomers and mixtures thereof, and thus is not limited by the expression of a representative formula.

Either of the isomers or a mixture of isomers is acceptable. Accordingly, a compound according to the present invention can sometimes have an optically active substance and a racemic form, which will not limit the present invention and both of these are included in the present invention. A compound can sometimes have a crystalline polymorphism, which will not limit the present invention. An individual crystalline substance as well as a mixture of crystalline substances is acceptable. In addition, examples of a compound according to the present invention may include anhydrates and solvates (particularly hydrates). In addition, the so-called metabolite produced by the in vivo degradation of a compound (1) according to the present invention can be included in the present invention. In addition, the present invention includes compounds (the so-called prodrugs) that produce a compound (1) according to the present invention through metabolism in vivo through oxidation, reduction, hydrolysis, and conjugation, etc. In a compound according to the present invention represented by the formula (1) mentioned above, a salt is formed in the NH group of the first or third positions of a benzimidazole structure. "Salt" is not particularly limited as long as it is pharmaceutically acceptable. Examples of said salt include salts of inorganic bases and salts of organic bases. Preferred examples of salts of inorganic bases include alkali metal salts such as sodium salt, potassium salt, and lithium salt; the alkaline earth metal salts such as calcium salt and magnesium salt; transition metal salts such as zinc salt; aluminum salt; and salt of ammonium. Preferred examples of the organic salts include the diethylamine salt, the diethanolamine salt, the neglumin salt and the N ', N'-dibenzylethylenediamine salt. The "solvate" of the present invention is not particularly limited so long as it is pharmaceutically acceptable. Examples of such solvents include a hydrate, an ethanol solvate, and an acetone solvate. The preferred example is a hydrate. Of the compounds represented by the formula (1) of the present invention, the preferred compounds include (2) a compound wherein R 1 is a hydrogen atom or a methyl group or a salt thereof, or a solvate thereof; (3) a compound wherein R1 is a methyl group, or a salt thereof, or a salt thereof; (4) a compound wherein R2 is a group represented by Formula 3 wherein W represents a hydrogen atom, a C1-C6 alkyl group or a halogen atom (provided that, the occurrence of W2 in the benzene ring may be from 1 to 3, and may be the same or different); ni represents 1 to 5, n2 represents 1 to 4; and n3 represents 1 to 6, the group optionally has 1 or 2 groups selected from group A2 consisting of a fluorine atom, a methyl group, an ethyl group, a propyl group, a methoxy group and a monofluoromethyl group; or a salt thereof, or a solvate thereof; (5) a compound wherein R2 is represented by Formula 4 or a salt thereof or solvate thereof; (6) a compound wherein R2 is represented by Formula 5 or a salt thereof or a solvate thereof; (7) a compound wherein R3 is a hydrogen atom or a methyl group, or a salt thereof or a solvate thereof; (8) a compound wherein R3 is a methyl group, or a salt thereof or a solvate thereof; (9) a compound wherein R 4 is a hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a fluorine atom, or a salt thereof, or a solvate; (10) a compound wherein R4 is a hydrogen atom, a methyl group, or a fluorine atom, or a salt thereof, or a solvate thereof; (11) a compound wherein R is an atom of hydrogen, or a salt thereof, or a solvate thereof; (12) a compound wherein R5 is a hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a methoxy group, an ethoxy group, or a fluorine atom, or a salt itself, or a solvate thereof; (13) a compound wherein R5 is a hydrogen atom, a methyl group, or a fluorine atom, or a salt thereof, or a solvate thereof; (14) a compound wherein R5 is a hydrogen atom, or a salt thereof, or a solvate thereof; (15) a compound wherein R6 is a hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a methoxy group, an ethoxy group or a fluorine atom, or a salt thereof, or a solvate thereof; (16) a compound wherein R6 is a hydrogen atom, a methyl group, or a fluorine atom or a salt thereof, or a solvate thereof. (17) a compound wherein R6 is a hydrogen atom, or a salt thereof, or a solvate thereof; (18) a compound wherein R7 is a hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a methoxy group, an ethoxy group, or a fluorine atom, or a salt thereof, or a solvate of these; (19) a compound wherein R7 is a hydrogen atom, a methyl group, or a fluorine atom, or a salt thereof, or a solvate thereof; (20) a compound wherein R7 is a hydrogen atom, or a salt thereof, or a solvate thereof; (21) a compound wherein W1 is an individual bond, a methylene group, or an ethylene group, or a salt thereof, or a solvate thereof; (22) a compound wherein W1 is a methylene group, or a salt thereof, or a solvate thereof; (23) a compound wherein 2 is a hydrogen atom, or a salt thereof, or a solvate thereof; (24) a compound wherein neither is from 1 to 3 or a salt thereof, or a solvate thereof; (25) a compound wherein neither is 1 or 2, or a salt thereof, or a solvate thereof; (26) a compound wherein n2 is 1 or 2, or a salt thereof, or a solvate thereof; (27) a compound wherein n3 is 1 to 4, or a salt thereof, or a solvate thereof; and (28) a compound wherein n3 is 1 or 2, or a salt thereof, or a solvate thereof. In addition, preference can be given to using a compound in the salt thereof, or a solvate of these satisfying the following conditions in any combination; R1 is selected from (2) or (3); R2 is selected from (4) or (6); R3 is selected from (7) or (8); R4 is selected from (9) to (11); R5 is selected from (12) to (14); R6 is selected from (15) a (17); R7 is selected from (18) to (20); and W1 is selected from (21) or (22), W2 is selected from (23), or selected from (24) or (25), n2 is selected from (26), n3 is selected from (27) or (28). Of the compounds or specific salts thereof or solvates thereof, suitable compounds of the present invention include 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) - 3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2 - (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2 - (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] unde-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole; 2- (((-4 ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole; 2- (((3-methyl-4- (2- (8-methyl-l, 4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) 1 -H-benzimidazole; 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((4- (2- (8-ethyl-l, 4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-ylmethyl) sulfinyl) -lH-benzimidazole; 2- (((4- (1, 3-dioxolan-4-ylmethoxy) -3-met ilpyridin-2-yl) methyl) sulfinyl) -IH-benzimidazole; 2 - (((4 - ((2,2 -bis (f luoromethyl) -1, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole; 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((4- ((2-methoxy-1,3-dioxan-5-yl) methyloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2 - (((3-methyl-4- ((8-methyl-1, 4,7,9-tetraoxaspiro [4.5] dec -8-yl) methoxy) pyridin-2-yl) met i 1) sulfinyl) -lH-benzimidazole; 2- (((4- (5,9-dioxaspiro [3.5] non-7-i lmeto i) pyridin- 2-yl) methyl) sulfinyl-lH-benzimidazole, or 2- (((4- ((5,5-difluoro-l, 3-dioxan-2-yl) methoxy) -3-methy lpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole, or salts thereof, or solvates thereof (particularly, anhydrous or hydrates of their sodium salts).

In addition, suitable compounds of the present invention include 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2 - (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole; or 2 - (((4 - ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1H-benzimide zol; or salts thereof, or solvates thereof (particularly, anhydrous or hydrates of their sodium salts). Of the optical isomers (presently existing) of the compounds mentioned above, it is more preferably the use made of a compound that exhibits more excellent inhibitory effects against the secretion of gastric acid a compound more excellent in terms of the persistence of the inhibitory effect against secretion of gastric acid. ADVANTAGES OF THE INVENTION The compound of the present invention has an excellent inhibitory effect against the secretion of gastric acid, more excellent persistence of the inhibitory effect against the secretion of gastric acid, maintains high intragastric pH for a long time, and has a more safe and appropriate physicochemical stability. Accordingly, the compound is useful as a medicine, particularly as a therapeutic agent or prophylactic agent for diseases or symptoms related to acid, and as a bactericidal agent or auxiliary bactericidal agent against Helicobacter pylori. DETAILED DESCRIPTION OF THE INVENTION The compound of the present invention can be produced by any of the methods described below; however, the production method of the present invention is not limited thereto. A compound (1) according to the present invention can be produced by method A below.

Formula 6 METHOD A wherein R1, R2, R3, R4, R5, R6, R7, and W1 are the same as defined above and X2 represents a leaving group. Examples of the leaving group of X2 include sulfonyloxy groups such as the methanesulfonyloxy, p-toluenesulfonyloxy, and trifluoromethanesulfonyloxy groups, and halogen groups such as chlorine, bromine, and iodine, acyloxy groups such as acetyloxy, trifluoroacetyloxy, and propionyloxy, and preferably methanesulfonyloxy and p. Toluenesulfonyloxy, chlorine and acetyloxy are used. Now, the individual steps of Method A will be explained below. Step A-1 Introduction of a leaving group or halogenation. (1) Reaction to introduce a leaving group. In this step, a compound (3) is reacted with an introducing agent of the leaving group in the absence of a solvent or in an inert solvent and in the presence of a base to produce a compound (3a) or a salt thereof. The solvent used here is not particularly limited as long as it can dissolve a starting material to some degree and does not inhibit the reaction. Examples of said solvent include halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene and benzotrifluoride; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; amides such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, triamidahexamethylphosphoric; and pyridine; and mixtures of these solvents. Preferably, they are halogenated hydrocarbons, ethers or a solvent mixture of ethers and aromatic hydrocarbons, and more preferably, dichloromethane, tetrahydrofuran, or one of tetrahydrofuran and toluene solvents. Examples of the leaving group introduction agent used herein include sulfonating agents such as methanesulfonyl chloride, p-toluenesulfonyl chloride, trifluoromethanesulfonyl chloride, N-phenyl-bis (trifluoromethanesulfonimide). Preferably, methanesulfonyl chloride or p-toluenesulfonyl chloride, and more preferably methanesulfonyl chloride is used. Examples of the base used herein include tertiary alkylamines such as trimethylamine and triethylamine; pyridine, potassium carbonate, sodium carbonate, sodium hydroxide, and potassium hydroxide. Preferably, triethylamine or sodium hydroxide is used, and more preferably, triethylamine. The reaction temperature varies depending on the starting material, the solvent, the introduction agent of the outgoing group, and the base. The reaction temperature is generally from -50 ° C to 100 ° C, and preferably from 20 ° C to 40 ° C. The reaction time varies depending on the starting material, the solvent, the leaving group production agent, the base, and the reaction temperature. The reaction time is generally from 15 minutes to 12 hours, and more preferably, from 30 minutes to 2 hours. The compound obtained in this step can not be particularly isolated and directly subjected to the next step. (2) Halogenation (taking chlorination as a representative example). In this step, a compound (3) is reacted with a chlorinating agent in the absence of a solvent or an inert solvent and in the presence or absence of a base to produce a compound (3a). The solvent used here is not particularly limited as long as it can dissolve a starting material to some degree and does not inhibit the reaction. Examples of said solvent include halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene, and benzotrifluoride; and ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether. Preferably a halogenated hydrocarbon or an aromatic hydrocarbon, and more preferably dichloromethane, chloroform or toluene are used. Examples of chlorinating agents that are used herein include methanesulfonyl chloride, oxalyl chloride, thionyl chloride, phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride, and hydrochloric acid; and preferably, thionyl chloride or hydrochloric acid are used. Base examples that are used herein include tertiary alkylamines such as trimethylamine and triethylamine; and pyridine; etc. Preferably, triethylamine is used. The reaction temperature varies depending on the starting material, solvent and chlorination agent. The reaction temperature is generally from -20 ° C to 30 ° C, and preferably from 0 ° C to 10 ° C. The reaction time depends on the starting material, solvent, chlorination agent, and reaction temperature. The reaction time is generally 10 minutes to 6 hours, and preferably, 10 minutes to 2 hours. The compound in this step can not be isolated particularly and directly subjected to the next step. Bromination is carried out through the use of a reagent such as red bromide / phosphorus, phosphorus tribromide, and phosphorus pentabromide. The ionization is carried out out through the use of a reagent such as iodine / red phosphorus. Alternatively, a bromine and iodine can be obtained through the reaction of a reagent such as sodium bromide and sodium iodide respectively with the leaving group synthesized in step A-1. Step A-2 Thioetherification In this step, a compound (2) is reacted with a compound (3a) or a salt thereof (particularly, salt (s) of hydrochloride) in the absence of a solvent or in an inert solvent and in the presence or absence of a base, to produce a compound (4). The solvent used here is not particularly limited as long as it can dissolve a starting material to the same degree and does not inhibit the reaction. Examples of said solvent include alcohols such as ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methylcellosolve; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene and toluene; N, N-dimethylformamide; dimethyl sulfoxide; water, and solvent mixtures of these. Preferably, they are used preferably dichloromethane, an alcohol, an ether or solvent mixtures of an ether and toluene, and more preferably, methanol, tetrahydrofuran or solvent mixtures of tetrahydrofuran and toluene. Examples of the base used herein include inorganic bases such as sodium hydride, potassium hydride, lithium carbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, and potassium hydroxide; organic bases such as N-methylmorpholine, triethylamine, tripopilamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picoline, 4- (N, N-dimethylamino) pyridine, 2,6-di ((t- butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,4-diazabicyclo [2.2.2. ] octane (DABCO), and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) .Preferably, an inorganic base such as sodium hydride, potassium hydride, lithium hydroxide, sodium hydroxide or hydroxide of potassium, or triethylamine, and more preferably, sodium hydroxide or triethylamine is used.The reaction temperature varies depending on the starting material, solvent and base, and is generally 0 ° C to 100 ° C, and preferably 10 ° C. C at 50 ° C. The reaction time varies depending on the starting material, solvent, base, and reaction temperature; and it's usually from 30 minutes to 3 days. Step A-3 Oxidation In this step, a compound (4) is reacted with an oxidation agent in the presence or absence of a solvent to produce a compound (1). The solvent used here is not particularly limited as long as it can dissolve a starting material to some degree and does not inhibit the reaction. Examples of such solvents include alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; amides such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, and hexamethylphosphoric triamide; nitriles such as acetonitrile. Preferably, an aromatic hydrocarbon, an alcohol, a halogenated hydrocarbon or a mixture of solvents thereof, and more preferably, toluene, a solvent mixture of toluene and methanol or dichloromethane is used. Examples of oxidation agents that are used here include hydrogen peroxide, t-butyl hydroperoxide, eumenohydroperoxide, sodium perhydrate, acid peracetic acid, perbenzoic acid, 3-chloroperbenzoic acid, urea hydrogen peroxide addition compound ((NH2) 2CO.H202). Preferably, 3-chloroperbenzoic acid or eumenohydroperoxide is used. Note that asymmetric oxidation can be carried out according to the methods described in the following documents; WO96 / 02535, WO2001 / 183473, WO2004 / 087702, WO2004 / 052881, WO2004 / 05882, Adv. Synth Catal. 2005, 347, 19-31., Chem. Rev. 2003, 103, 3651-3705., Tetrahedron Lett. 2004, 45, 9249-9252., Angew. Chem. Int. Ed. 2004, 43, 4225-4228., And Tetrahedron Asymmetry 2003, 14, 407-410. More specifically, asymmetric oxidation is carried out through the reaction of a compound (4), and an oxidation agent in the presence of an asymmetric induction agent or an asymmetric induction catalyst. Examples of oxidation agents include peroxides such as hydrogen peroxide, tert-butyl hydroperoxide, urea hydroperoxide, eumenohydroperoxide, in particular, when an asymmetric induction agent or asymmetric induction catalyst contains titanium, zirconium, or hafnium, the eumeno hydroperoxide. When it contains vanadium, hydrogen peroxide is used. The oxidizing agent that is used here can be present in an amount that exceeds that of the compound (4) preferably falls within the range of 1.01 to 10 moles equivalent. In particular, when an asymmetric induction agent or asymmetric induction catalyst contains titanium, 1.05 equivalents of the oxidation agent are used. When an asymmetric induction agent or asymmetric induction catalyst contains zirconium or hafnium, 1.2 equivalents of the oxidation agent are used.

When it contains vanadium, 1.1 equivalents of the oxidizing agent are generally used. Examples of the asymmetric induction agent or the asymmetric induction catalyst include (1) optimally active titanium complexes such as the complexes of an optically active diol and titanium (IV) alkoxide and water or an alcohol; (2) zirconium complexes optically active such as complexes of an optically active and zirconium alkoxide (IV) diol (water may be present or not present) (3) a hafnium complex optically active such as complex of a diol Optimally active and hafnium alkoxide (IV); (4) an optimally active vanadium complex such as the complexes of an optimally active Schiff base and vanadyl acetylacetone; (5) Optimally active iron complexes such as the complexes of an optimally active Schiff base and iron (III) acetylacetone; (6) optimally active manganese complexes (eg, a salt-manganese complex) such as the complexes of an optimally active Schiff base and manganese; and (7) optimally active tungsten complexes such as the complexes of an optimally active Cinchona alkaloid and tungsten (III). Examples of the optimally active diol include (1) alkyl diols such as esters of tartaric acid, for example, (+) or (-) dimethyl tartrate, diethyl tartrate, diisopropyl tartrate, and dibutyl tartrate; and tartaramide such as tetramethyl tartaramide; and (2) an aromatic diol such as (R) - or (S) -blackphol. (- -) -2- (3, 5-di-tert-butilsalicilidenamino) -3, 3-dimethyl-l-butanol examples Schiff base optimally active Schiff bases derived from the substituted aldehydes salicido such as (S) include , and (IR, 2S) -1- ((2-hydroxy-3,5-di-tert-butylbenzylidene) amino) indan-2-ol, and salt-like Schiff bases. When asymmetric oxidation was carried out, if necessary, a base is added. Examples of the base that used are not particularly unlimited as long as they do not inhibit a reaction and include inorganic bases and organic bases, preferably, tertiary amines such as diisopropylethylamine and triethylamine, and more preferably diisopropylethylamine. The base is generally added in an amount of 0.1 to 1 equivalent in relation to the compound (4) Note that an asymmetric induction agent or asymmetric induction catalyst containing vanadium is used, generally no base is used. Examples of the solvent that is used in asymmetric oxidation include aromatic hydrocarbons such as toluene, benzene, and xylene; halogenated hydrocarbons such as dichloromethane and chloroform; and esters such as ethyl acetate. Particularly, when an asymmetric induction agent or asymmetric induction catalyst containing titanium, zirconium or hafnium is used, preferably toluene or tert-butylmethyl ether is used. When an asymmetric induction agent or asymmetric induction catalyst containing vanadium is used, acetonitrile or dichloromethane is preferably used. When an asymmetric induction catalyst containing titanium is used, the addition of water is effective. The amount of water includes the water contained in a solvent, in a reaction agent (excluding an oxidizing agent) and the substrate preferably falls within the range of 0.1 to 0. 33 equivalents relative to the compound (4), and more preferably, 0.13 to 0.25 equivalents. The water content can be controlled through 3A molecular sieves. When a complex of titanium (IV) alkoxide and an alcohol is synthesized, isopropanol is effectively used as the alcohol, usually in the amount of 1.2 equivalents relative to titanium. The reaction temperature varies depending on the starting material, the solvent, and the oxidation agent; and is generally from -100 ° C to 100 ° C, and more preferably from -70 ° C to 70 ° C. The reaction time varies depending on the starting material, the solvent, an oxidation agent, and the reaction temperature; and it is generally from 15 minutes to 72 hours, and more preferably from 30 minutes to 24 hours. The compound obtained above can be converted into a salt by a conventional method. More specifically, a compound (1) is reacted with a base in the presence or absence of a solvent. As a solvent, acetonitrile is used; an alcohol such as methanol or ethane; water or a solvent mixture thereof, and preferably, a mixture of ethanol and water solvents. As the base, use is made of an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide, or potassium hydroxide; an alkaline earth metal hydroxide, such as magnesium hydroxide; and an alkoxide such as sodium methoxide, sodium t-butoxide, sodium t-pentoxide, or magnesium methoxide. Preferably, an aqueous solution of sodium hydroxide is used. The reaction temperature is generally from -50 to 50 ° C, and more preferably from 10 to 40 ° C. The reaction time is generally from 1 minute to 2 hours and preferably from 1 minute to 1 hour. Alternatively, an alkali metal salt such as sodium salt and potassium salt can be subjected to a salt exchange reaction with a metal chloride or a metal sulfate such as barium chloride, magnesium chloride, magnesium sulfate, or zinc sulfate in the presence or absence of a solvent to convert it into the corresponding metal salts such as barium salt, magnesium salt, and zinc salt. After a compound (4) is oxidized, a compound (1) can be subjected to conversion into a salt without subjecting it to an isolation operation to obtain a metal salt. When a compound (2) and a compound (3), which are intermediates in method A, use is made of commercially available compounds or readily produced compounds of commercially available compounds according to a conventional method that one skilled in the art can usually carry out. Especially, a compound (3) is It can produce according to method B as mentioned below. Formula 7 Method B (3) In the formula, R1, R2, R3, and W1 are the same as defined above; and X1 represents a halogen atom, preferably a chlorine atom, a bromine atom, or an iodine atom, and more preferably a chlorine atom. Now, the following steps will be explained Individuals of method B. (Step Bl) Halogenation (taking chlorination as a representative reaction) In this step, a compound (5) is reacted with a chlorinating agent in the absence of a solvent or an inert solvent to produce a compound (6) In this step, the reaction is desirably carried out in a chlorinating agent generally without using a solvent. However, when a solvent is used, the solvent is not particularly limited as long as it can dissolve a starting material to a degree and does not inhibit the reaction. Examples of such solvents include halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; and ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and dimethoethane, and diethylene glycol dimethyl ether. Examples of chlorinating agent that are used herein include acetyl chloride, oxalyl chloride, thionyl chloride, phosphorus oxychloride, phosphorus trichloride, and phosphorus pentachloride, and acetyl chloride is preferably used. The reaction temperature depends on the particulate material, the solvent and the chlorination agent; and is generally from -50 ° C to 30 ° C, and preferably from -30 ° C to 10 ° C.

The reaction time varies depending on the starting material, the solvent, the chlorination agent and the reaction temperature; and it is generally from 30 minutes to 8 hours, and more preferably from 1 to 6 hours. When bromination is carried out, a reagent such as acetyl bromide, hydrogen bromide, red bromide / phosphorus, phosphorus tribromide, and phosphorus pentabromide is used. When the iodization is carried out, a reagent such as iodine / red phosphorus is used or the bromination is carried out and then the sodium iodide is reacted. (Step B-2) Reaction of the introduction of the group R2-W1-0 In this step, a compound (6) is reacted with an alcohol (7) which is a group R2-W1-OH (wherein R2 and W1 they are the same as defined above, in the absence of a solvent or in an inert solvent and in the presence of a base, to produce a compound (8) The solvent used here is not particularly limited as long as it can dissolve a starting material Examples of such solvent include aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; aromatics such as benzene and toluene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol, dimethyl ether; amides such as formamide, N, N-dimethylformamide, N, N-dimethylacetamide, hexamethylphosphoric triamide, and N-methylpyrrolidone; Dimethylsulfoxide; Water; and mixtures of these solvents. Preferably, dimethyl sulfoxide is used; an ether, or an amide and more preferably dimethylsulfoxide. Examples of the base used herein include alkali metal carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; metal alkoxide such as lithium methoxide, sodium methoxide, sodium ethoxide, and potassium t-butoxide; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; Alkali metal alkoxides prepared through an alkali metal; n-butyl lithium; and lithium diisopropylamide. Preferably, the alkali metal hydride, and more preferably sodium hydride, is used. The reaction temperature varies depending on the starting material, the solvent and the base; and is generally from 0 ° C to 100 ° C, and preferably from 10 ° C to 100 ° C in the case where the alcohol (7), i.e. R2-W1-OH is an alcohol primary; and from 50 to 100 ° C in the case where the alcohol is a secondary alcohol. The reaction time varies depending on the starting material, the solvent, the base and the reaction temperature; and it is generally from 15 minutes to 48 hours, and more preferably from 30 minutes to 12 hours. Step B-3 Reconfiguration of the acety acid ester. In this step, a compound (8) is reacted with acetic anhydride in the absence of a solvent and the presence or absence of a base to produce an acetate of the compound (3). Examples of the base used herein include tertiary amines such as trimethylamine, diisopropylethylamine and triethylamine; and pyridine; etc. Preferably triethylamine is used. The reaction temperature varies depending on the starting material and the solvent; and is generally from 20 ° C to 150 ° C, and preferably from 20 ° C to 60 ° C in the presence of a base, and from 50 to 100 ° C in the absence of a base. The reaction time varies depending on the starting material, the solvent, and the reaction temperature; and it is generally, from 10 minutes to 6 hours, and preferably, from 30 minutes to 5 hours. After the reaction, the residue obtained by the distillation of the acetic anhydride is usually submit directly to the next step. Alternatively, the acetate is subjected to step A-2 of method A to obtain a compound (4). (Step B-4) Hydrolysis reaction In this step, the compound obtained in step B-3 is reacted with a base in the presence or absence of a solvent to produce a compound (3). The solvent used here is not particularly limited as long as it can dissolve a starting material to some degree and does not inhibit the reaction. Examples of said solvent include water; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol, and methyl cellosolve; aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; amides such as formamide, N, N-dimethylformamide; N, N-dimethylacetamide, and dimethylformamide; N, -dimethylacetamide, and triamidahexamethylphosphoric; and solvent mixtures of these. Preferably, an alcohol or solvent mixture of an alcohol and water is used, and more preferably, a solvent mixture of methanol and water.

Examples of the base used herein include alkali metal carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate.; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide, and potassium t-butoxide; and ammonia such as aqueous ammonia, and concentrated ammonia-methanol, etc. Preferably, an alkali metal hydroxide, and more preferably sodium hydroxide, is used. The reaction temperature varies depending on the starting material, the solvent and the base; and is generally from 0 ° C to 60 ° C, and more preferably from 10 ° C to 40 ° C. The reaction time varies depending on the starting material, the solvent, the base and the reaction temperature; and it's generally from 10 minutes to 6 hours. In each of the methods, after the completion of the reaction in each step, a target compound of a reaction mixture can be obtained according to a conventional method. For example, in the case where the complete reaction mixture is a solution, an objective compound is obtained by returning the temperature of the reaction mixture if necessary to room temperature or by cooling the reaction mixture on ice, neutralizing an acid, alkali, agent of oxidation, or reducing agent, and adding water and an organic solvent such as ethyl acetate not miscible with water and not reactive with a target compound, therefore separating a layer containing the target compound and thereafter adding a solvent not miscible to the obtained layer and not reactive to the objective compound, washing the layer containing the target compound, and separating the layer. Further, if the obtained layer is an organic layer, the desired compound can be obtained by drying the organic layer by using a dehydrating agent such as potassium carbonate, anhydrous magnesium sulfate or anhydrous sodium sulfate and distilling the solvent On the other hand, if the layer obtained is a layer of water, the desired compound can be obtained by subjecting the layer to electric desalination and lyophilization steps. Alternatively, when the complete reaction mixture is a solution, and if possible, the target compound can be obtained through the distillation of the other compounds (eg, solvent, reagent) under normal pressure or reduced pressure. Further, when only one target compound is precipitated as a solid or the entire reaction mixture is a liquid and only one target compound is precipitated in the course of the recovery process, the target compound can be obtained through a filtration, washing of the objective compound filtered with a suitable solvent, and dried. In addition, the objective compound can be obtained from the filtrate and the same way as in the case of the complete reaction mixture is a solution, additionally. In addition, when a reagent (s) or a catalyst is present only as a solid in the reaction mixture, or in the case where the complete reaction mixture is a solution, apart from a reagent (s) or a catalyst it only precipitates As a solid in the course of the recovery process and the target compound is dissolved in the solvent, the objective compound can be obtained by filtering the reagent (s) or catalyst, washing the filtered reagent (s) or the catalyst with a suitable organic or inorganic solvent, cning the washing liquid and the filtrate, treating the mixture in the same way as in the case of the complete reaction mixture is a solution. In particular, in the case where other compounds apart from the objective compound contained in the reaction mixture do not inhibit the reaction of the next step, the mixture can be used directly in the next step without isolation of the target compound. To improve the purity of the objective compound obtained in the aforementioned step, a recrystallization method can be appropriately applied, several chromatographic methods and a distillation method. When the objective compound obtained is a solid, the purity of the objective compound is generally improved by the recrystallization method. In the recrystallization method, a single solvent or a mixture of solvents of a plurality of solvents not reactive to the target compound can be used. More specifically, a target compound can be recrystallized first through the solution of the target compound in a single solvent or a mixture of solvents of a plurality of solvents at room temperature or with heating, and then, cooling the resulting solution with ice water, etc., shake it or let it stand alone at room temperature, or add a solvent in which the objective dissolves at a low solubility, thus recovering the crystallized target compound from the solution. The purity of the target compound can be improved by various chromatographic methods. Generally, silica gel column chromatography can be used using weak acid silica gels such as silica gel 60 (70 to 230 mesh or 340 to 400 mesh) manufactured by Merck Ltd., BW-300 (meshes) of 300) manufactured by Fuji Silesia Chemical Ltd., or a medium pressure liquid chromatography disposable silica gel column (high flash column), manufactured by Yamazen Corporation. When a target compound is basic and excessively adsorbed by the silica gels mentioned above, use is made of a silica gel coated with propyl amine (meshes of 200 to 350) manufactured by Fuji Silesia Chemical Ltd., or NH silica gel as used in the disposable silica gel column cartridge for medium pressure liquid chromatography (Frash Alto, Amino) manufactured by Yamazen Corporation. Alternatively, when a target compound has a bipolarity or must be eluted through a high polar solvent such as methanol, NAM-200H or NAM-300H (manufactured by NAM Laboratory) can be used. When a target compound is eluted through the use of any of these silica gels and a single solvent or solvent mixture of a plurality of solvents not reactive with the target compound, and the solvent is removed, the compound improved in purity is you can get. When the obtained target compound is liquid, the purity of the target compound can be improved through the distillation method. In the distillation method, a target compound can be distilled at normal pressure or through reduced pressure at room temperature, or with heating. In the above, a representative method of manufacturing a compound (1) has been explained. The starting compounds and the reagents for uses in the The manufacture of a compound according to the present invention can be a salt or a solvate such as a hydrate, which varies depending on the starting material and the solvent to be used, and are not particularly limited as long as they can not inhibit the reaction. Needless to say, the solvent to be used varies depending on the starting materials and reagents and is not particularly limited as long as it does not inhibit the reaction and can dissolve a starting material to some degree. When a compound (1) according to the present invention can be obtained in a free form, it can be converted into a salt or solvate, to which the compound (1) can be converted, according to a conventional method. When a compound (1) according to the present invention is obtained in the form of a salt or a solvate of the compound (1), the salt or the solvate can be converted into a compound in free form (1) according to a method conventional In addition, various isomers (such as geometric isomers, optical isomers, rotational isomers, stereoisomers, and tautomers) of a compound (1) according to the present invention are purified and isolated through conventional separation means, for example, a recrystallization method, diastereomeric salt method, enzymatic separation method, various methods chromatographic (such as, thin layer chromatography, column chromatography and gas chromatography) When the compound of the present invention is used as a medicament, usually, the compound is mixed with appropriate additives to be a formulation, which is put into use . However, in the case where the compound of the present is directly used as a medicament, it is not eliminated. Examples of such additives include an excipient, a binder, lubricant, disintegrator, colorant, flavor and odor improver, emulsifier, surfactant, solubilizer, suspending agent, isotonic agent, pH regulator, preservative, antioxidant, stabilizer, and accelerator. absorption that are usually used in medicine. If desired, they can be used in combination. Examples of excipients include lactose, white sugar, glucose, corn starch, mannitol, sorbitol, starch, starch, dextrin, crystalline cellulose, light anhydrous salicylic acid, aluminum silicate, calcium silicate, magnesium aluminometasilicate, and acid phosphate of calcium. Examples of binders include polyvinyl alcohol, methylcellulose, ethylcellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, and macrogol. Examples of lubricants include magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, polyethylene glycol, and colloidal silica. Examples of disintegrants include crystalline cellulose agar, gelatin, calcium carbonate, sodium acid carbonate, calcium citrate, dextrin, pectin, low-substitution cellulose hydroxypropyl, carboxymethylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, carboxymethyl starch, Sodium carboxymethyl starch. Examples of dyes include pharmaceutically acceptable dyes such as iron sesquioxide, yellow iron sesquioxide, carmine, caramel, β-carotene, titanium oxide, talc, riboflavin sodium phosphate, and yellow aluminum lake. Examples of flavor and odor improver include cocoa powder, menthol, perfumed powder, menthol oil, Borneo camphor, and cinnamon powder. Examples of emulsifiers or surfactants include stearyl triethanolamine, sodium lauryl sulfate, laurel aminopropionic acid, lecithin, glycerin monostearate, sucrose fatty acid ester, and glycerin fatty acid ester. Examples of solubilizers include polyethylene glycol, propylene glycol, benzoate benzyl, ethanol, cholesterol, triethanolamine, sodium carbonate, sodium citrate, polysorbate 80, and nicotinamide. Examples of suspending agent include other of the aforementioned surfactants, hydrophilic polymers such as polyvinyl alcohol, polyvinyl, pyrrolidone, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. Examples of isotonic agents include glucose, sodium chloride, mannitol and sorbitol. Examples of pH regulators include pH buffer solutions of phosphate, acetate, carbonate and citrate. Examples of preservatives include methyl paraben, propyl paraben, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, and sorbic acid. Examples of antioxidants include sulfite, ascorbate, and α-tocopherol. As examples of stabilizers, those generally used in medicine are mentioned. As examples of absorption accelerator, those generally used in medicine are mentioned. Examples of preparations include peroral agents such as tablets, powders, granules, capsules, syrups, troches, and inhalers; external preparations such as suppositories, ointments, ointments for the eyes, tape agent, eye drops, nose drops, ear drops, poultices, and lotions; and injections. The peroral agents mentioned above are prepared through the appropriate combination of the compound of the present invention with the aforementioned additives. Observe that, if necessary, the surface of the preparations can be covered. The external preparations are formed through the appropriate combination of the compound of the present invention with the aforementioned additives, in particular, an excipient, binder, flavor and odor improver, emulsifier, surfactant, solubilizer, suspending agent, isotonic agent , preservative, antioxidant, stabilizer, and absorption accelerator. The injections are prepared through the appropriate combination of the compound of the present invention with the aforementioned additives, in particular, an emulsifier, surfactant, solubilizer, suspending agent, isotonic agent, pH regulator, preservative, antioxidant, stabilizer, and absorption accelerator. When the compound of the present invention is used as a medicament, the doses vary depending on the symptom and age; however, generally from 0.15 to 5000 mg (preferably, 0.5 to 1500 mg) in the case of a peroral agent, 0.5 to 15000 (preferably, 1.5 to 500 mg) in the case of an external preparation, 0.3 to 5000 mg (preferably 1 to 500 mg) in the case of an injection. The dose amount can be administered once, or through division in 2 to 6 times per day. Observe that in the cases of the peroral agent and the injection the dose is the amount virtually administered, while in the external preparation, the dose indicates a quantity virtually absorbed in the living body. A compound (1) of the present invention can be produced through a method shown in the following examples. The effect of the compound can be confirmed by the method described in the test examples (below). These examples are described by way of example but will not limit the present invention in any way. The names of commercially available starting materials and reagents used in the Examples and manufacturers thereof are shown below. The name of the documents is shown in the available manufacturer's column, meaning that the compound is formed according to the method described in the document. Benzyloxyacetaldehyde (Aldrich), 2,2-Dimethyl-1,3-propandiol (Kanto Chemical Co., Inc.), p-Toluenesulfonic acid monohydrate (Tokyo Kasei Kogio Co., Ltd.), % Palladium hydroxide (Aldrich), Sodium hydride, in oil (Wako Pure Chemical Industries Ltd.), Acetone (Wako Pure Chemical Industries Ltd.) 4-Chloro-2,3-dimethylpyridine-oxido (obtained from Sanyo Fine Co., Ltd .; however it is a known compound described in J. Med. Chem. 1998, 41, 1777-1788), Acetic anhydride (Kanto Chemical Co., Inc.), 5N of Aqueous sodium hydroxide solution (Wako Pure Chemical Industries Ltd. ), IN of Aqueous sodium hydroxide solution (Wako Pure Chemical Industries Ltd.), Triethylamine (Kanto Chemical Co., Inc., or Wako Pure Chemical Industries Ltd.), Methanesulfonyl chloride (Tokyo Kasei Kogio Co., Ltd.), 2-Mercaptobenzimidazole (Tokyo Kasei Kogio Co, Ltd.), 3-Chloroperbenzoic acid (Tokyo Kasei Kogio Co., Ltd.), 1,1-Bis (hydroxymethyl) cyclopropane (Aldrich) ethyl 3-oxohexanoate (ACROS) Ethylene glycol (Tokyo Kasei Kogio Co., Ltd.) , Lithium-aluminum hydride (Wako Pure Chemical Industries Ltd.), 1,3-Dibenzyloxy-2-propanol (Aldrich) Pyridine sulfur trioxide complex (Aldrich) Triethyl orthoformate (Wako Pure Chemical Industries Ltd.), trimethyl orthoformate (Tokyo Kasei Kogio Co., Ltd.), Methyl propionylacetate (Aldrich) Hydroxyacetone (Wako Pure Chemical Industries Ltd.), Benzoyl Chloride (Tokyo Kasei Kogio Co., Ltd.), D- (-) -diethyl tartrate (Tokyo Kasei Kogio Co., Ltd.), Toluene (dehydrated) (Kanto Chemical Co., Inc.), Titanium (IV) Isopropoxide (Kanto Chemical Co., Inc. or Aldrich), N, N-Diisopropylethylamine (Aldrich or Nakarai Tesque) Cumene Hydroperoxide (Nakarai Tesque, Inc. or Aldrich) L- (+) - Diethyl Tartrate (Tokyo Kasei Kogio Co., Ltd. or Aldrich), 2- (Hydroxymethyl) -1,3-propanediol (E-MERCK or Aldrich), Tetrahydrofuran (dehydrated) (Kanto Chemical Co., Inc.), 1,3-Difluoroacetone (SINQUEST) 1, 3-Propanediol (Wako Pure Chemical Industries Ltd.), ((4R) -2, 2-dimethyl-1,3-dioxolan-4-yl) methanol (Aldrich) 2,2-dimethyl-1,3-dioxan -5-ona (Tokyo Kasei Kogio Co., Ltd.), Benzyl bromide (E-MERCK) Tetrabutylammonium iodide (Tokyo Kasei Kogio Co., Ltd.), DOWEX (R) 50W-X8 (Muromachi Kagaku Kogio Kaisha, Ltd.) Cyclobutanone (AVOCADO) Tetrahydro-4H-pyran-4-one (Tokyo Kasei Kogio Co., Ltd.), Dichloromethane (dsehydrate) (Kanto Chemical Co., Inc.), 70% Perchloric Acid (Wako Pure Chemical Industries Ltd.), 2,3,5-Colidin (ACROS), Sulfuric Acid (Junsei Chemical Co., Ltd.), Nitric Acid, Smoking (Wako Pure Chemical Industries Ltd.), Acetyl Chloride (Junsei Chemical Co., Ltd.), N, N-dimethylformamide (Wako Pure Chemical Industries Ltd.), O ÍN Aqueous sodium hydroxide solution (Wako Pure Chemical Industries Ltd.), Sodium hydroxide (Wako Pure Chemical Industries Ltd.), p-Toluenesulfonyl chloride (Tokyo Kasei Kogio Co., Ltd.), Thionyl Chloride (Wako Pure Chemical Industries Ltd.), Potassium T-butoxide (Tokyo Kasei Kogio Co., Ltd.), Pentaerythritol (Tokyo Kasei Kogio Co., Ltd.), Triethyl Ortoacetate ( Tokyo Kasei Kogio Co., Ltd.), Triethyl Ortopropionate (Tokyo Kasei Kogio Co., Ltd.), 3-Pentanone (Tokyo Kasei Kogio Co., Ltd.), Cyclopentanone (Tokyo Kasei Kogio Co., Ltd.), Cyclohexanone (Tokyo Kasei Kogio Co., Ltd.), Monoetylene ketal 1,4-Cyclohexanedione (Tokyo Kasei Kogio Co., Ltd.), Cyclopropanecarbonitrile (Tokyo Kasei Kogio Co., Ltd.), Cyclobutanecarbonitrile (AVOCADO), Benzyloxyacetaldehyde ( Aldrich), l-Benzyloxy-2-propanone (Aldrich), Picolinic acid (Tokyo Kasei Kogio Co., Ltd.), 2, 2-Dimethyl-l, 3-propanediol (Kanto Chemical Co., Inc.) Ethyl acetoacetate (Tokyo Kasei Kogio Co., Ltd.), 4-Methoxyacetoacetate of methyl (Tokyo Kasei Kogio Co., Ltd.), Ethyl iodide (Wako Pure Chemical Industries Ltd.) Diisopropylamine (Aldrich), n-Butyl-lithium (Kanto Chemical Co., Inc.), Lithium aluminum hydride (Wako Pure Chemical Industries Ltd.), Sodium Borohydride (Kanto Chemical Co., Inc.), 2N Aqueous Sodium Hydroxide Solution (Wako Pure Chemical Industries Ltd.), Hydrogen Gas (TOMOE SHOKAI Co., LTD), Acid Gas hydrochloric acid (TOMOE SHOKAI Co., LTD), ethyl 3-Oxopentanoate (Aldrich), l-Bromobutan-2-one (Trans World Chemicals, Inc.), Potassium Acétate (Wako Pure Chemical Industries Ltd.), Potassium carbonate (Kanto Chemical Co., Inc.), Methyl 4-methoxyacetoacetate (Tokyo Kasei Kogio Co., Ltd.) Dihydroxyacetone (E-MERCK), Pyridine (Wako Pure Chemical Industries Ltd.), Benzoyl Chloride (Tokyo Kasei Kogio Co., Ltd.), 1,8-Diazabicyclo [5.4.0] undec-7-ene (Aldrich), nonafluoro-1-butanesulfonyl fluoride (Tokyo Kasei Kogio Co., Ltd.), Sodium Benzoate (Kanto Chemical Co., Inc.), (Diethylamino) sulfur trifluoride (FLUKA), 28% sodium methoxide methanol solution (Wako Pure Chemical Industries Ltd .), Benzyloxyacetaldehyde (Aldrich), 3-Hydroxy-2-methylpyridine (Aldrich) N-phenyltrifluoromethanesulfonimide (Tokyo Kasei Kogio Co., Ltd.), (Trimethylsilyl) acetylene (Aldrich), Bis (triphenylphosphine) palladium (II) Chloride (NE CHEMCAT), copper iodide (I) (Kanto Chemical Co., Inc.), tetrabutylammonium fluoride (solution of IN tetrahydrofuran) (Aldrich), 10% Palladium / carbon (NE CHEMCAT), 3, -Diamino-l-fluorobenzene (Lancaster), Carbon Disulfide (Wako Pure Chemical Industries Ltd.), Dimethyl acetaldehyde (Tokyo Kasei Kogio Co., Ltd.), Lithium bromide (Aldrich) p-Toluenesulfonic acid monohydrate (Tokyo Kasei Kogio Co., Ltd.), 2-Methyl-6-nitroaniline (Wako Pure Chemical Industries Ltd.), 4-Nitro-2-picoline N-oxide ( Lancaster), 0.1N Aqueous sodium hydroxide solution (Wako Pure Chemical Industries Ltd.), 5, 5-Dimethyl-1, 3-dioxan-2-ethanol (Aldrich), Glycerol formal (Tokyo Kasei Kogio Co., Ltd .), 2-Hydroxymethyl-l, 4-benzodioxane (Aldrich), 2- (Allyloxy) ethanol (Tokyo Kasei Kogio Co., Ltd.), Iodine (Wako Pure Chemical Industries Ltd.), 18-Crown-6 (Wako Pure Chemical Industries Ltd.), Zirconium Isopropoxide (IV) Complex / isopropanol (Aldrich), (-) -Tetramethyl- (D) -tartaramide (Tokyo Kasei Kogio Co., Ltd.), Hafnium Tetrabutoxide (Aldrich), Vanadyl Acetylacetone (Aldrich), (S) - (-) - 2- (3,5-Di-tert-butylsalicylideneamino) -3,3-Dimethyl-1-butanol (Aldrich), 30% acid peroxide (Kanto Chemical Co., Inc.), 3-Amino-4-nitrotoluene (Aldrich ), 2-Methoxy-6-nitroaniline (J. of Chem. Soc. (1954) 2977-2978), 4-Amino-3-nitrobenzotrifluoride (ACROS), 4- (2-Hydroxyethyl) -2, 2-dimethyl-1,3-dioxolane (Aldrich), DL-aO-Benzylglycerol (SIGMA), 3- Pentanone (Tokyo Kasei Kogio Co., Ltd.), l-Benzyloxy-2-propanone (Aldrich), (+) -1, 4-Dioxaspiro [4,5] decan-2-methanol (Aldrich) 4-Benzyloxy-2 -butanone (FLUKA), (R) - (+) -1,2, 4-Butantriol (Wako Pure Chemical Industries Ltd.), (S) - (-) -1, 2, 4-Butanetriol (Wako Pure Chemical Industries Ltd.), Methyl acetoacetate (Tokyo Kasei Kogio Co., Ltd.) 6,7-Dihydro-lH- [1,4] dioxino [2 ', 3': 4,5] benzo [D] imidazole-2-thiol (MAIBRIDGE), 5-Nitro-l, 3-benzodioxole (Tokyo Kasei Kogio Co., Ltd.), Tetramethylammonium nitrate (Aldrich), trifluoromethanesulfonic anhydride (Aldrich), methyl 2-cyclopentanonecarboxylate (Aldrich), mono-2, 2-dimethyltrimethylene ketal 1,4-Cyclohexanedione (Aldrich). Methyl 4-cyclohexanonecarboxylate (Tokyo Kasei Kogio Co., Ltd.) Diethyl acetal glycol aldehyde (Lancaster), diethyl 1,1-cyclobutanedicarboxylate (Lancaster) EXAMPLES In the formulas described in the Examples, the atom marked with the reference mark *, represents an asymmetric atom. Example 1 Solium salt of 2- (((- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1 H -benzimidazole sodium Na (la) 2- ((benzyloxy) methyl) -5,5-dimethyl-l, 3-dioxane Formula 9 To a mixture of benzyloxyacetaldehyde (5 g, 33.3 mmol), 2,2-dimethyl-1,3-propandiol (4.16 g, 40 mmol) and toluene (70 ml), p-toluenesulfonic acid monohydrate (287 mg, 1.51 g) was added. mmoles) and refluxed for 4 hours while the water was removed by the Dean-Stark apparatus. After cooling the reaction mixture temperature At room temperature, triethylamine (4 ml) was added to the reaction mixture and the solvent was removed by evaporation. The residue was purified by column chromatography on silica gel (silica gel: 200 g, eluting solvent: ethyl acetate / heptane = 1/9) to obtain the title compound (7.6 g, yield: 96.6%) as a colorless oil. XH NMR (400 MHz, CDC13) d ppm; 0.73 (3H, s), 1.19 (3H, s), 3.46 (2H, d, J = 10 Hz), 3.55 (2H, d, J = 4 Hz), 3.64 (2H, d, J = 10 Hz), 4.60 (2H, s), 4.66 (1H, t, J = 4 Hz), 7.26-7.35 (5H, m). (lb) (5, 5-dimethyl-l, 3-dioxan-2-yl) methanol The 2- ((benzyloxy) methyl) -5,5-dimethyl-1,3-dioxane (7.6 g, 32.2 mmol) obtained in step (a) was mixed with % palladium hydroxide (700 mg) and ethyl acetate (70 ml). The mixture was stirred under a hydrogen atmosphere overnight. The reaction mixture was allowed to stand for 5 more days in the same hydrogen atmosphere. The reaction vessel was purged with nitrogen, the catalyst was filtered, and the solvent was distilled to obtain the title compound (4 g, yield: 85%) as a white solid. XH NMR (400 MHz, CDC13) d ppm; 0.75 (3H, s), 1.20 (3H, s), 1.88-1.95 (HH, br), 3.47 (2H, d, J = 10 Hz), 3.63-3.66 (4H, m), 4.54 (HH, t, J = 4 Hz). (lc) 4- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -2, 3-dimethylpyridine oxide The (5,5-dimethyl-1,3-dioxan-2-yl) methanol (2 g, 13.7 mmol) obtained in step (lb) was mixed with sodium hydride in oil (822 mg, 20.6 mmol according to the content estimated as 60%) and dimethyl sulfoxide (20 ml). The mixture was stirred at room temperature for 30 minutes. To the reaction mixture, 1-oxide 4-chloro-2,3-dimethylpyridine (2.16 g, 13.7 mmol) was added and stirred at 50 ° C overnight, and was also allowed to stand immobile for one day at room temperature . After the dimethylsulfoxide was distilled, methanol and water were added to the residue and then the methanol was distilled. The mixture of the reaction mixture and NH silica gel was purified by column chromatography on silica gel (NH silica gel: 200 g, eluting solvent: ethyl acetate / heptane = 1 / L-> 4; methanol / ethyl acetate = l / 9) to obtain the title compound (3.1 g, yield: 84.6%) as a light yellow oil. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.70 (3H, s), 1.12 (3H, s), 2.12 (3H, s), 2.34 (3H, s), 3.49 (2H, d, J = ll Hz), 3.59 (2H, d, J = ll Hz ), 4.06 (2H, d, J = 4 Hz), 4.82 (1H, t, J = 4 Hz), 6.96 (1H, d, J = 7 Hz), 8.05 (1H, d, J = 7 Hz). (ld) (4- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methanol Formula 12 The 1-oxide 4- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -2,3-dimethylpyridine (3.1 g, 11.6 mmol) obtained by step (lc) was mixed with anhydride acetic acid (9.87 ml, 104 mmol). After the mixture was stirred at 85 ° C. for 45 minutes, the acetic anhydride was removed. The residue was dissolved in methanol (40 ml) and a solution of 5N aqueous sodium hydroxide (5.1 ml, 25.5 mmol) was added to the mixture while cooling on ice. The mixture was stirred at room temperature for one hour. The methanol was distilled and ice water was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate. After the solvent was distilled off, the resulting mixture was purified by column chromatography on silica gel (silica gel: 120 g, eluting solvent: ethyl acetate / heptane = 1/4 to 4/1) to obtain the title compound. title (1.23 g, yield: 39.7%) as a light yellow oil.

XH NMR (400 MHz, CDC13) d ppm; 0.77 (3H, s), 1.23 (3H, s), 2.07 (3H, s), 3.52 (2H, d, J = 12 Hz), 3.69 (2H, d, J = 12 Hz), 4.12 (2H, d , J = 4 Hz), 4.65 (2H, s), 4.85 (1H, t, J = 4 Hz), 6.73 (1H, d, J = 6 Hz), 8.30 (1H, d, J = 6 Hz). (le) 2- (((4- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 13 The (4- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methanol (500 mg, 1.87 mmol) obtained by step (ld) was mixed with triethylamine (1.04 ml, 7.48 mmol) and tetrahydrofuran (15 ml). This mixture was cooled to -19 ° C and methanesulfonyl chloride (217 μL, 2.81 mmol) was added thereto and then stirred -19 ° C for 30 minutes. Under the same conditions, 2-mercaptobenzimidazole (309 mg, 2.06 mmol) was added to the reaction mixture. After the reaction mixture was stirred overnight at room temperature, methanol and NH silica gel were added to the mixture, and then, the solvent was distilled. The mixture of the reaction mixture and NH silica gel was purified by gel column chromatography. silica (silica gel: 80 g, eluting solvent: ethyl acetate / heptane = 1 / L-> methanol / ethyl acetate = 1/9) to obtain the title compound (599 mg, yield: 80.2%) as a clear red foam. 1 H NMR (400 MHz, DMSO-d 6) d ppm; 0.71 (3H, s), 1.13 (3H, s), 2.21 (3H, s), 3.50 (2H, d, J = ll Hz), 3.59 (2H, d, J = ll Hz), 4.09 (2H, d , J = 4 Hz), 4.69 (2H, s), 4.84 (1H, t, J = 4 Hz), 6.98 (1H, d, J = 6 Hz), 7.11 (2H, dd, J = 3, 6 Hz ), 7.36-7.51 (2H, br), 8.22 (1H, d, J = 6 Hz). (lf) 2- (((4- ((5,5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole For- 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole (599 mg, 1.5 mmoles) obtained by step (le) was mixed with methanol (5 ml) and toluene (15 ml), and the mixture was cooled to -50 ° C. 3-Chlorobenzoic acid (358 mg, 1.35 mmol, depending on the estimated content as 65%) dissolved in a mixture of methanol solvent and toluene was added dropwise to the mixture, and was stirred from -47 ° C to -70 ° C for 3 hours. A saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over potassium carbonate, and the solvent was distilled. The residue was purified by column chromatography on silica gel (NH silica gel: 40 g, eluting solvent: dichloromethane / heptane = 7 / 3-> methanol / dichloromethane = 3/97 to 1/9). To the obtained product, heptane (20 ml) and diethyl ether (2 ml) were added, the precipitate was obtained through filtration. In this form, the title compound (475 mg, yield: 76.2%) was obtained as an orange solid. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.71 (3H, s), 1.12 (3H, s), 2.14 (3H, s), 3.49 (2H, d, J = ll Hz), 3.59 (2H, d, J = ll Hz), 4.09 (2H, d , J = 4 Hz), 4.70 (1H, d, J = 13 Hz), 4.78 (1H, d, J = 13 Hz), 4.84 (1H, t, J = 4 Hz), 6.98 (1H, d, J = 6 Hz), 7.25-7.32 (2H, m), 7.60-7.66 (2H, m), 8.20 (1H, d, J = 6 Hz). (lg) Sodium salt of 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H- Benzimidazole Formula 15 2- (((4- ((5, 5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3- methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (475 mg, 1.14 mmol) obtained by step (1) was mixed with ethanol (15 ml). To the mixture, an IN of aqueous sodium hydroxide solution (1.14 ml, 1.14 mmol) was added and the solvent distilled. Ethanol was added to the residue, dissolved and distilled. This operation was repeated twice. Diethyl ether was added to the residue and the resulting mixture was treated ultrasonically. The precipitate was obtained through filtration and dried by aspiration to obtain the title compound (445 mg, yield: 89.2%) as a light yellow solid. 1 H NMR (400 MHz, DMSO-d 6) d ppm; 0.70 (3H, s), 1.13 (3H, s), 2.18 (3H, s), 3.50 (2H, d, J = ll Hz), 3.59 (2H, d, J = ll Hz), 4.08 (2H, d , J = 4 Hz), 4.39 (1H, d, J = 13 Hz), 4.76 (1H, d, J = 13 Hz), 4.84 (1H, t, J = 4 Hz), 6.85 (2H, dd, J = 3, 6 Hz), 6.95 (1H, d, J = 6 Hz), 7.43 (2H, dd, J = 3, 6 Hz), 8.27 (1H, d, J = 6 Hz). EXAMPLE 2 Sodium salt of 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 16 (2a) 6- ((benzyloxy) methyl) -5,7-dioxasprio [2.5] octane Formula 17 A mixture of benzyloxyacetaldehyde (5 g, 33.3 mmol), 1,1-bis (hydroxymethyl) cyclopropane (4.08 g, 40 mmol), p-toluenesulfonic acid monohydrate (287 mg, 1.51 mmol) and toluene (70 ml) was brought to reflux for 2 hours while the water was removed by the Dean-Stark apparatus. After cooling the reaction mixture to room temperature, triethylamine (4 ml) was added to the reaction mixture and the solvent was distilled off. The residue was purified by column chromatography on silica gel (silica gel: 200 g, eluting solvent: ethyl acetate / heptane = 5/95 to 1/9) to obtain the title compound (6.1 g, yield: 78.2%) as a light yellow oil. XH NMR (400 MHz, CDC13) d ppm; 0.31-0.35 (2H, m), 0.67-0.71 (2H, m), 3.26 (2H, d, J = 12 Hz), 3.57 (2H, d, J = 4 Hz), 4.14 (2H, d, J = 12 Hz), 4.60 (2H, s), 4.82 (1H, t, J = 4 Hz), 7.27-7.34 (5H, m). (2b) 5, 7-dioxaspiro [2.5] oct-6-ylmethanol Formula 18 6- ((Benzyloxy) methyl) -5,7-dioxasprio [2. 5] octane (6.1 g, 26 mmol) obtained by step (2a) was mixed with 20% palladium hydroxide (800 mg) and ethyl acetate (70 ml) and the mixture was stirred under a hydrogen atmosphere for 24 hours. The reaction vessel was purged with nitrogen and the catalyst was filtered and then the solvent was distilled to obtain the title compound (3.7 g, yield: 98.7%) as a colorless oil. XH NMR (400 MHz, CDC13) d ppm; 0.33-0.37 (2H, m), 0.68-0.72 (2H, m), 3.28 (2H, d, J = 12 Hz), 3.68 (2H, d, J = 4 Hz), 4.16 (2H, d, J = 12 Hz), 4.73 (1H, t, J = 4 Hz). (2c) 4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -2, 3-dimethylpyridine-1-oxide Formula 19 The 5,7-dioxaspiro [2.5] oct-6-ylmethanol (1.7 g, 11.8 mmol) obtained by step (2b) was mixed with sodium hydride, in oil (708 mg, 17.7 mmol, according to the estimated content as 60%). ) and dimethylsulfoxide (20 ml), and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture, 1-oxide 4-chloro-2,3-dimethylpyridine (1.86 g, 11.8 mmol) was added and stirred at 50 ° C overnight. After the dimethylsulphoxide was distilled, Methanol and NH silica gel were added to the residue and methanol was distilled. The mixture of the reaction mixture and NH silica gel was purified by column chromatography on silica gel (silica gel NH: 200 g, eluting solvent: ethyl acetate / heptane = 1 / la / l- > methanol / ethyl acetate = 1/9 to 1/4) to obtain the title compound (1.8 g, yield: 57.5%) as a red oil. XH NMR (400 MHz, CDC13) d ppm; 0.36-0.40 (2H, m), 0.69-0.74 (2H, m), 2.22 (3H, s), 2.53 (3H, s), 3.30 (2H, d, J = 12 Hz), 4.1K2H, d, J = 4 Hz), 4.19 (2H, d, J = 12 Hz), 5.00 (1H, t, J = 4 Hz), 6.68 (1H, d, J = 7 Hz), 8.13 (1H, d, J = 7 Hz). (2d) (4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methanol Formula 20 The 1-oxide of 4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -2,3-dimethylpyridine (1.8 g, 6.78 mmol) obtained by step (2c) was mixed with acetic anhydride (5.77 ml). , 61 mmol). The mixture was stirred at 85 ° C for 45 minutes and then the acetic anhydride was distilled. The residue was cooled on ice and dissolved in methanol. To this, a solution of 5N aqueous sodium hydroxide (2.98 ml, 14.9 ml) was added. mmoles) under cooling with ice and the mixture was stirred at room temperature for 2 hours. The methanol was distilled and water was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with a saturated saline solution and dried over anhydrous magnesium sulfate, and then the solvent was distilled off. Purification was carried out by column chromatography on silica gel (silica gel: 100 g, eluting solvent: ethyl acetate / heptane = 1/4 to 4/1). To the purified product, heptane (15 ml) was added and the mixture was brought to reflux. After it was confirmed that the solution reached a homogeneous state, it gradually cooled. The precipitated product was obtained through filtration. In this form, the title compound (520 mg, yield: 28.9%) was obtained as a white solid. XH NMR (400 MHz, CDC13) d ppm; 0.36-0.40 (2H, m), 0.70-0.74 (2H, m), 2.07 (3H, s), 3.30 (2H, d, J = ll Hz), 4.14 (2H, d, J = 4 Hz), 4.20 (2H, d, J = ll Hz), 4.64 (2H, s), 4.86 (1H, br s), 5.02 (1H, t, J = 4 Hz), 6.73 (1H, d, J = 6 Hz), 8.29 (1H, d, J = 6 Hz). (2e) 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 21 (4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methanol (520 mg, 1.96 mmol) obtained in step (2d) was mixed with triethylamine (1.09 ml. 7.84 mmole) and tetrahydrofuran (10 ml) and the resulting mixture was cooled to -19 ° C. Methanesulfonyl chloride (228) [mu] l, 2.94 mmole) to the mixture, which was stirred -19 ° C by minutes. Under the same conditions, 2-mercaptobenzimidazole (324 mg, 2.16 = moles) was added to the reaction mixture. After the reaction mixture was stirred at room temperature for 2 days, methanol and NH silica gel were added to the mixture, and the solvent was distilled. The mixture of the reaction mixture and NH silica gel was purified by column chromatography on silica gel (silica gel: 80 g, eluting solvent: ethyl acetate / heptane = 4/6 to 7 / 3- > methanol / ethyl acetate = l / 9) to obtain the title compound (629 mg, yield: 80.7%) as a colorless foam.

[0264] 1 H NMR (400 MHz, DMSO-d6) d ppm; 0.31-0.36 (2H, m), 0.56-0.6K2H, m), 2.21 (3H, s), 3.26 (2H, d, J = 12 Hz), 4.10-4.13 (4H, m), 4.69 (2H, s ), 5.02 (1H, t, J = 5 Hz), 6.99 (1H, d, J = 6 Hz), 7.11 (2H, dd, J = 3, 6 Hz), 7.39-7.49 (2H, br), 8.23 (1H, d, J = 6 Hz). (2f) 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 22 The 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole (629 mg, 1.58 mmol) obtained by the step (2e) was mixed with methanol (5 ml) and toluene (15 ml) and the mixture was cooled to -50 ° C. Then, 3-chlorobenzoic acid (378 mg, 1.42 mmol according to the estimated content as 65%) dissolved in a mixture of methanol solvent and toluene was added dropwise to the mixture, and was stirred from -47 ° C to -70. ° C for 4 hours. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over potassium carbonate, and the solvent was distilled. The residue was purified by column chromatography on silica gel (NH silica gel: 40 g, eluting solvent: dichloromethane / heptane = 7 / 3- > methanol / dichloromethane = 3/97 to 1/9) to obtain the title compound (623 mg, yield: 95.4%) as a colorless foam. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.31-0.36 (2H, m), 0.56-0.6K2H, m), 2.14 (3H, s), 3.26 (2H, d, J = ll Hz), 4.11- 4.13 (4H, m), 4.70 (1H, d , J = 14 Hz), 4.79 (1H, d, J = 14 Hz), . 02 (1H, t, J = 4 Hz), 6.99 (1H, d, J = 6 Hz), 7.29 (2H, dd, J = 3, 6 Hz), 7.59-7.67 (2H, br), 8.21 (1H, d, J = 6 Hz). (2g) 2 - (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole sodium salt Formula 23 The 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (623 mg, 1.51 mmol) obtained in the Step (2f) was mixed with ethanol (15 ml). To the mixture, a solution of aqueous sodium hydroxide IN (1.51 ml, 1.51 mmol) was added and the solvent was distilled. Ethanol was added to the residue and distilled. This operation was repeated twice. Ethyl ether was added to the residue and the resulting mixture was treated ultrasonically. He The precipitate was obtained by filtration and dried by aspiration to obtain the title compound (553 mg, yield: 84.1%) as a white solid. ? NMR (400 MHz, DMSO-d6) d ppm; 0.31-0.35 (2H, m), 0.57-0.61 (2H, m), 2.19 (3H, s), 3.26 (2H, d, J = ll Hz), 4.10 (2H, d, J = 5 Hz), 4.12 (2H, d, J = ll Hz), 4.37 (1H, d, J = 13 Hz), 4.82 (1H, d, J = 13 Hz), 5.02 (1H, t, J = 5 Hz), 6.84 (2H , dd, J = 3, 6 Hz), 6.95 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.27 (1H, d, J = 6 Hz). Example 3 Sodium salt of 2- (((3-methyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -1 H- Benzimidazole Formula 24 3a) (2-propyl-l, 3-dioxolan-2-yl) ethyl acetate A mixture of ethyl 3-oxohexanoate (5 g, 31. 6 mmoles), ethylene glycol (3.92 g, 63.2 mmol) and triethyl orthoformate (4.68 g, 31.6 mmol), and p-acid toluenesulfonic monohydrate (544 mg, 2.86 mmol) was stirred at room temperature for 29 hours and 10 minutes. To the reaction mixture, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (6.2 g, 97%) as a colorless oil. 1 H NMR (400 MHz, CDC13) d ppm; 0.93 (3H, t, J = 7 Hz), 1.27 (3H, t, J = 7 Hz), 1.39-1.48 (2H, m), 1.78 (2H, t, J = 8 Hz), 2.64 (2H, s ), 3.94-4.02 (4H, m), 4.15 (2H, q, J = 7H). (3b) 2- (2-propyl-l, 3-dioxolan-2-yl) ethanol Formula 26 To a suspension of tetrahydrofuran (100 ml) of lithium aluminum hydride (1.17 g, 30.7 mmol), a solution of tetrahydrofuran (20 ml) of (2-propyl-1,3-dioxolan-2-yl) acetate was added. of ethyl (6.2 g, 30.7 mmoles) obtained in step (3a) under cooling with ice. The mixture was stirred for 30 minutes under ice-cooling, water (1.17 ml) and a solution of 15% aqueous sodium hydroxide (1.17 ml) and water (3.51 ml) were added sequentially and stirred for 10 minutes. Sodium sulfate was added to the mixture was stirred and subjected to filtration with silica gel.

The filtrate was concentrated under reduced pressure and the residue dissolved in a solution mixture containing n-heptane / ethyl acetate in a ratio of 2: 1 and column chromatography was subjected to silica gel (elution solvent: n-heptane ethyl acetate = 2/1) to obtain the title compound (3.82 g, 77.7%) as a colorless oil. XH NMR (400 MHz, CDC13) d ppm; 0.93 (3H, t, J = 8 Hz), 1. 33-1.43 (2H, m), 1.60-1.65 (2H, m), 1.92 (2H, t, j = 6 Hz), 2.83 (1H, t, J = 6 Hz), 3.74 (2H, q, J = 6 Hz), 3.95-4.03 (4H, m). (3c) 2,3-dimethyl-4- (2- (2-propyl-l, 3-dioxolan-2-yl) ethoxy) pyridine-1-oxide Formula 27 To a solution of dimethyl sulfoxide (22.5 ml) of the 2- (2-propyl-1,3-dioxolan-2-yl) ethanol (1.5 g, 9.35 mmol) obtained in step (3b), sodium hydride was added, oil (561 mg, 14 mmol according to the estimated content as 60%) and 1-oxide of 4-chloro-2,3-dimethylpyridine (1.33 g, 8.42 mmol) in a stream of nitrogen and stirred at 60 ° C for 2 hours . The mixture was allowed to stand at room temperature for 3 hours. days and concentrated under reduced pressure. The residue was suspended in tetrahydrofuran. NH silica gel was added to the resulting mixture, which was then concentrated to dryness and subjected to column chromatography on NH silica gel (eluting solvent: n-heptane / ethyl acetate / methanol = 1 / l / 0- > 0 / l / 0-> 0/10 / l) to obtain the title compound (1.53 g, yield: 58.2%) as a light brown oil. 2 H NMR (400 MHz, CDC13) d ppm; 0.94 (3H, t, J = 7 Hz), 1.38-1.49 (2H, m), 1.62-1.67 (2H, m), 2.14-2.20 (2H, m), 2.19 (3H, s), 2.53 (3H, s), 3.92-4.01 (4H, m), 4.10 (2H, t, J = 7 Hz), 6.64 (1H, d, J = 7 Hz), 8.13 (1H, d, J = 7 Hz). (3d) (3-Methyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl acetate Formula 28 The 2,3-dimethyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridine 1-oxide (1.53 g, 5.44 mmol) obtained in step (3c) was mixed with acetic anhydride (30 ml) and the mixture was stirred at 80 ° C overnight. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate and then subjected column chromatography on silica gel (elution solvent: n-heptane / ethyl acetate = 1 / L) to obtain the title compound (1.19 g, 67.6%) as a light yellow oil. H NMR (400 MHz, CDC13) d ppm; 0.94 (3H, t, J = 7 Hz), 1. 39-1.49 (2H, m), 1.64-1.69 (2H, m), 2.12 (3H, s), 2.16-2.20 (2H, m), 2.18 (3H, s), 3.93-4.00 (4H, m), 4.12 (2H, t, J = 7 Hz), 5.20 (2H, s), 6.73 (1H, d, J = 6 Hz), 8.31 (1H, d, J = 6 Hz). (3e) (3-Methyl-4- (2- (2-propyl-l, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methanol Formula 29 Ethyl (3-methyl-4- (2- (2-propyl-l, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) acetate (1.19 g, 3.68 mmol) obtained in step (3d) ) was mixed with a solution of aqueous sodium hydroxide IN (5 ml) and methanol (10 ml). The mixture was stirred at room temperature for 3 hours and concentrated under reduced pressure. The residue was suspended in tetrahydrofuran and sodium sulfate was added to the suspension, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in a solution mixture containing heptane and ethyl acetate at a ratio of 2: 1 and column chromatography on silica gel (elution solvent: n-heptane / ethyl acetate = 2/1) was subjected to obtain the title compound (0.88 g, 85%) as a colorless oil. XH NMR (400 MHz, CDC13) d ppm; 0.94 (3H, t, J = 7 Hz), 1. 39-1.49 (2H, m), 1.64-1.69 (2H, m), 2.03 (3H, s), 2.18 (2H, t, J = 7 Hz), 3.93-4.01 (4H, m), 4.14 (2H, t, J = 7 Hz), 4.65 (2H, s), 4.89 (1H, br s), 6.73 (1H, d, J = 6 Hz), 8.29 (1H, d, J = 6 Hz). (3f) 2- (((3-Methyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 30 The (3-methyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methanol (450 mg, 1.6 mmol) obtained in step (3e) is mixed with tetrahydrofuran (10 ml). The mixture was cooled on ice under a nitrogen atmosphere. To this, triethylamine (0.446 ml, 3.2 mmol), and methanesulfonyl chloride (0.186 ml, 2.4 mmol) were added and stirred for 50 minutes under cooling with ice cooling. To the reaction mixture, 2-mercaptobenzimidazole (240 mg, 1.6 mmol) was added and stirred at room temperature overnight. To the reaction mixture, an aqueous solution of sodium acid carbonate was added and extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate. After adding silica gel to the solution, the solution was concentrated. The dried residue was subjected to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = 1 / l-> 0 / L) to obtain the title compound (528 mg, 79.8%) as a colorless viscous gel. 1ti NMR (400 MHz, CDC13) d ppm; 0.94 (3H, t, J = 7 Hz), 1. 39-1.50 (2H, m), 1.63-1.68 (2H, m), 2.20 (2H, t, J = 7 Hz), 2. 26 (3H, s), 3.93-4.01 (4H, m), 4.16 (2H, t, J = 7 Hz), 4.37 (2H, s), 6.78 (1H, d, J = 6 Hz), 7.16-7.20 (2H, m), 7.50-7.59 (2H, m), 8. 35 (ÍH, d, J = 6 Hz). (3g) 2- (((3-Methyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 31 2- (((3-Methyl-4- (2- (2-propyl-l, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) thio) -lH-benzimidazole (482 mg, 1. 17 mmoles) obtained in step (3f) was dissolved in a solvent mixture of toluene (30 ml) and methanol (3 ml). The mixture was cooled under a nitrogen atmosphere. To this mixture, a solution of methanol (1.3 ml) of 3-chlorobenzoic acid (311 mg, 1.17 mmol according to the estimated content as 65%) was added at an internal temperature below -70 ° C and stirred to below -60 ° C for 2 hours. To the reaction mixture, an aqueous solution of sodium hydrogen carbonate and ethyl acetate were added. The organic layer was separated and washed with a saturated saline solution, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in methylene chloride and column chromatography was subjected to silica gel using NH silica gel (eluting solvent: methylene chloride / methanol = l / 0-> 100 / l- > 100/5) to obtain the title compound (323 mg, yield: 64.3%). X H NMR (400 MHz, DMSO-d 6); 0.85 (3H, t, J = 7 Hz), 1.28- 1.39 (2H, m), 1.55-1.60 (2H, m), 2.04 (2H, t, J = 7 Hz), 2.10 (3H, s), 3.89 -3.90 (4H, m), 4.08 (2H, t, J = 7 Hz), 4.68 (1H, d, J = 13 Hz), 4.77.1H, d, J = 13 Hz), 6.95 (1H, d, J = 6 Hz), 7.26-7.32 (2H, m), 7.59-7.67 (2H, m), 8.20 (1H, d, J = 6 Hz). (3h) Sodium salt of 2- (((3-methyl-4- (2- (2-propyl-1,3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -1 H -benzimidazole Formula 32 2- (((3-Methyl-4- (2- (2-propyl-l, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (323 mg, 0.752 mmoles) obtained in step (3g) was mixed with ethanol (15 ml) and an aqueous IN sodium hydroxide solution (0.752 ml, 0.752 mmol) and the mixture was stirred at room temperature for 10 minutes. The solvent was distilled and the resulting residue was dissolved in ethanol and the solvent was distilled again. Diethyl ether-ethanol-n-heptane was added to the residue and stirred at room temperature and then filtered to obtain a solid. In this form, the title compound (315 mg, 92.8%) was obtained as a light yellow solid. X H NMR (400 MHz, DMSO-d 6); 0.85 (3H, t, J = 7 Hz), 1.29-1.39 (2H, m), 1.56-1.63 (2H, m), 2.05 (2H, t, J = 7 Hz), 2.15 (3H, s), 3.83 -3.9K4H, m), 4.07 (2H, t, J = 7 Hz), 4.40 (1H, d, J = 13 Hz), 4.76 (1H, d, J = 13 Hz), 6.84-6.90 (2H, m ), 6.92 (1H, d, J = 5 Hz), 7.41-7.47 (2H, m), 8.25 (1H, d, J = 5 Hz). Example 4 Sodium salt of 2- (((4- (2- (8-ethyl-1, 4, 7, 9- tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 33 (4a) 1, 3-bis (benzyloxy) acetone Formula 34 To a solution of dichloromethane (200 ml) of 1,3-dibenzyloxy-2-propanol (52 g, 191 mmol), triethylamine (130 ml, 933 mmol), and dimethyl sulfoxide (65 ml, 916 mmol), the complex was added of pyridine sulfur trioxide (131 g, 823 mmol) at 0 ° C and stirred at 0 ° C at room temperature for 2 hours. To the mixture, water and ethyl acetate were added. The organic layer was washed with 2N hydrochloric acid, water and an aqueous saline solution, dried over anhydrous sodium sulfate, and concentrated. As a result, the title compound (52.01 g, quantitative yield) was obtained as a brown oil. X H NMR (400 MHz, DMSO-d 6) d ppm; 4.26 (4H, s), 4. 49 (4H, s), 7.25-7.38 (10H, m). (4b) 2, 2-bis ((benzyloxy) methyl) -1,3-dioxolane Formula 35 The 1,3-bis (benzyloxy) acetone (30 g, 111 mmol) obtained in step (4a) was mixed with ethylene glycol (64 ml, 1.148 mmol) and triethyl orthoformate (19 ml, 114 mmol), and acid p-toluenesulfonic monohydrate (591 mg, 3.11 mmol). The mixture was stirred at 50 ° C for 14 hours. To the mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added. The organic layer was washed with water and a saline solution, dried over anhydrous sodium sulfate, and concentrated. The crude product obtained was purified by column chromatography on silica gel (elution solvent: heptane / ethyl acetate = 1 / 4-4 / 1 gradient) and the desired fractions were concentrated to obtain the title compound (28.46 g, yield: 81.6%) as a colorless oil. 1 H NMR (400 MHz, DMSO-d 6) d ppm; 3.45 (4H, s), 3.88 (4H, s), 4.50 (4H, s), 7.22-7.35 (10H, m). (4c) 1,3-dioxolan-2,2-diyldimethanol Formula 36 To a solution of ethyl acetate (300 ml) of 2,2-bis ((benzyloxy) methyl) -1,3-dioxolane (28.5 g, 90.7 mmol) obtained in step (4b), palladium hydroxide ( 20% by weight Pd (dry basis) on carbon, wet (max water 50%)) (2.5 g) and stirred at room temperature for 39 hours in a hydrogen atmosphere. After the reaction mixture was purged with nitrogen, a catalyst was filtered from the reaction mixture and washed with ethyl acetate. The filtrate was concentrated. To the obtained residue, ethyl acetate (300 ml) and palladium hydroxide (20 wt.% Pd (dry basis) on carbon, wet (max. 50% water)) (2.5 g) were added and stirred at room temperature. 26 hours in a hydrogen atmosphere. After the reaction mixture was purged with nitrogen, a catalyst was filtered and washed with ethyl acetate. The filtrate was concentrated to obtain the title compound (11.97 g, yield: 98.4%) as a colorless oil. X H NMR (400 MHz, DMSO-d 6) d ppm; 3.32 (4H, d, J = 6 Hz), 3.85 (4H, s), 4.63 (2H, t, J = 6 Hz). (4d) (8-ethyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8-yl) ethyl acetate Formula 37 The l, 3-dioxolan-2,2-diyl dimethanol (4 g, 29.8 mmol), which was obtained at another time in the same manner as described in steps (4a) - (4c), was mixed with methyl propionylacetate. (5.6 ml, 44.6 mmoles) and triethyl orthoformate (5.2 ml, 31.3 mmoles), and p-toluenesulfonic acid monohydrate (163 mg, 0.856 mmoles). The mixture was stirred at room temperature for 3 hours. To the mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added. The organic layer was washed with water twice and with an aqueous saline solution, dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by column chromatography on silica gel (elution solvent: heptane / ethyl acetate = 1 / 0.3 / ll / L gradient) and a fraction (s) was concentrated to obtain the title compound (2.63 g, yield: 35.8%) as a colorless oil. X H NMR (400 MHz, DMS0-d 6) d ppm; 0.84 (3H, t, J = 7 Hz), 1.75 (2H, q, J = 7 Hz), 2.76 (2H, s), 3.56 (3H, s), 3.58 (2H, d, J = 12 Hz), 3.68 (2H, d, J = 12 Hz), 3.80-3.89 (4H, m). (4e) 2- (8-ethyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8- il) ethanol Formula 38 To a THF solution (40 ml) of ethyl (8-ethyl-l, 4, 7, 9-tetraoxaspiro [4.5] dec-8-yl) ethyl acetate (2.63 g, 10.7 mmol) obtained in step (4d) , lithium aluminum hydride (487 mg, 12.8 mmol) was added at 0 ° C and stirred at 0 ° C at room temperature for 4 hours. Sequentially added water (0.5 ml), a 2N aqueous sodium hydroxide solution (0.5 ml), water (1.5 ml) to finish the reaction. Then, anhydrous sodium sulfate and celite were added to the mixture, the resulting mixture was filtered through a glass filter, and washed with ethyl acetate. The filtrate was concentrated to obtain the title compound (2.34 g, quantitative yield) as a colorless oil. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.79 (3H, t, J = 7 Hz), 1.62 (2H, q, J = 7 Hz), 1.81 (2H, t, J = 8 Hz), 3.41 (2H, dt, J = 6, 8 Hz), 3.57 (4H, s), 3.83 (4H, s), 4.29 (1H, t, J = 6 Hz). (4f) 4- (2- (8-ethyl-1,4,7,8-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -2, 3-dimethylpyridine Formula 39 To a solution of dimethyl sulfoxide (20 ml) of 2- (8-ethyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8-yl) ethanol (1.34 g, 6.14 mmol) obtained in step ( 4e), sodium hydride was added, in oil (295 mg, 7.37 mmoles according to the estimated content as 60%) at room temperature in a nitrogen atmosphere. The mixture was stirred for 30 minutes under the same conditions. To the reaction mixture, 1-oxide of 4-chloro-2,3-dimethylpyridine (1.06 g, 6.75 mmol) was added at room temperature and the resulting mixture was stirred at 60 ° C for 5.5 hours. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: heptane gradient, ethyl acetate / methanol = l / 0-4 / l) and a (s) desired fraction (s) to obtain the title compound (948 mg, yield: 45.5%) as a light yellow solid. X H NMR (400 Hz, DMSO-d 6) d ppm; 0.83 (3H, t, J = 7 Hz), 1.73 (2H, q, J = 7 Hz), 2.09 (3H, s), 2.12 (2H, t, J = 6 Hz), 2.32 (3H, s), 3.62 (4H, s), 3.80-3.88 (4H, m), 4.06 (2H, t, J = 6 Hz), 6.89 (1H, d, J = 8 Hz), 8.05 (1H, d, J = 8 Hz ). (4g) (4- (2- (8-ethyl-1,4,7,8-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl) methanol Formula 40 The 1-oxide of 4- (2- (8-ethyl-1,4,7,8-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -2,3-dimethylpyridine (947 mg, 2.79 mmol) obtained in step (4f) was mixed with acetic anhydride (10 ml). To the mixture, triethylamine (0.6 ml, 4.3 mmol) was added and stirred at 50 ° C for 2 hours. The reaction mixture was concentrated and methanol (10 ml) was added to the residue and then a solution of 5N aqueous sodium hydroxide (7 ml) was added and stirred at room temperature for one hour. To the mixture, a saturated aqueous ammonium chloride solution (7 ml) was added and the pH of the resulting solution was adjusted to about 10. The reaction mixture was diluted with ethyl acetate and the organic layer was washed with a 2N aqueous sodium hydroxide solution, water, and a saline solution, dried over anhydrous sodium sulfate, and concentrated. The crude product obtained was purified by column chromatography on silica gel (elution solvent: acetate gradient ethyl / methanol = l / 0-4 / l) and a desired fraction (s) was concentrated to obtain the title compound (564 mg, yield: 59.6%) as a light yellow solid. X H NMR (400 MHz, DMS0-d 6) d ppm; 0.8 (3H, t, J = 7 Hz), 1.74 (2H, q, J = 7 Hz), 2.08 (3H, s), 2.14 (2H, t, J = 6 Hz), 3. 63 (4H, s), 3.78-3.89 (4H, m), 4.08 (2H, t, J = 6 Hz), 4.50 (2H, d, J = 6 Hz), 4.96 (1H, t, J = 6 Hz ), 6.90 (1H, d, J = 6 Hz), 8. 20 (ÍH, d, J = 6 Hz). (4h) 2- (((4- (2- (8-ethyl-l, 4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl) methyl) thio ) -lH-benzimidazole Formula 41 To a THF solution (10 mL) of (4- (2- (8-ethyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl) methanol (560 mg, 1.65 mmol) obtained in step (4g), triethylamine (0.48 ml, 3.44 mmol) was added at room temperature and then methanesulfonyl chloride (0.19 ml, 2.45 mmol) was added while cooling in a bath of salt and stirred under the same conditions for 30 minutes. After removing the salt bath, 2-mercaptobenzimidazole (248 mg, 1.65 mmol) was added and stirred room temperature for 22 hours. After the reaction mixture was concentrated, NH silica gel was added to the residue and dried. The crude substance was purified by column chromatography on silica gel (elution solvent: heptane / ethyl acetate gradient = 1 / 0.1-0 / 1) and a desired fraction (s) was concentrated ( s). The obtained foam product was dissolved in chloroform and ethyl ether was added thereto. The resulting solid was collected through filtration to obtain the title compound (410 mg, yield: 52.7%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.84 (3H, t, J = 7 Hz), 1.75 (2H, q, J = 7 Hz), 2.15 (2H, t, J = 6 Hz), 2.18 (3H, s), 3.63 (4H, s), 3.80-3.90 (4H, m), 4.09 (2H, t, J = 6 Hz), 4.67 (2H, s), 6.93 (1H, d, J = 6 Hz), 7.07-7.13 (2H, m), 7.35 -7.51 (2H, m), 8.22 (1H, d, J = 6 Hz), 12.60 (1H, br s). (4i) 2- (((4- (2- (8-ethyl-l, 4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinil -lH-benzimidazole H To a solution of toluene (10.8 ml) and methanol (1.2 ml) of 2- (((4- (2- (8-ethyl-1,4,7,7-tetraoxaspiro [4.5] dec. 8-yl) ethoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole (380 mg, 0.81 mmol) obtained in step (4h), a solution of toluene (2.7 ml) was added dropwise. and methanol (0.3 ml) of 3-chlorobenzoic acid (192 mg, 0.73 mmol according to the estimated content as 65%) of -70 to -60 ° C for 10 minutes in a nitrogen atmosphere. The mixture was stirred for one hour under the same conditions. The reaction was terminated by the addition of a saturated aqueous solution (15 ml) of sodium acid carbonate at the same temperature. The mixture was extracted with chloroform (50 ml) twice and the organic layer was dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by column chromatography on silica gel (NH silica gel: eluting solvent: ethyl acetate / methanol gradient = 1 / 0-4 / l) and the desired fractions were concentrated. The product in the form of a foam was dissolved and re-precipitated with chloroform and diethyl ether and filtered. The operation was repeated four times and the solid obtained was washed with diethyl ether and then dried to obtain the title compound (188 mg, 47.9% yield) as a white solid. X NMR (400 MHz, DMSO-d6) d ppm; 0.83 (3H, t, J = 7 Hz), 1.74 (2H, q, J = 7 Hz), 2.10 (3H, s), 2.14 (2H, t, J = 6 Hz), 3.63 (4H, s), 3.79-3.90 (4H, m), 4.09 (2H, t, J = 6 Hz), 4.68 (1H, d, J = 13 Hz), 4.77 (1H, d, J = 13 Hz), 6.93 (1H, d , J = 6 Hz), 7.23-7.32 (2H, m), 7.54-7.68 (2H, m), 8.20 (1H, d, J = 6 Hz). (4j) Sodium salt of 2- (((4- (2- (8-ethyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl ) methyl) sulfinyl) -lH-benzimidazole Formula 43 To a solution of ethanol (2 ml) of 2- (((4- (2- (8-ethyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin- 2-yl) methyl) sulfinyl) -lH-benzimidazole (188 mg, 0.39 mmol) obtained in step (4i), a solution of IN aqueous sodium hydroxide (386 [mu] l, 0.39 mmol) was added at room temperature environment, and the mixture was stirred for 10 minutes, and then concentrated. Methanol was added to the residue and the concentration was carried out. After this operation was repeated, ethyl ether was added to the residue and the obtained suspension allowed to stand. After removing the supernatant, the residue was dried by a vacuum pump to obtain the title compound (190 mg, 96.6% yield) as a white solid. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.84 (3H, t, J = 8 Hz), 1.75 (2H, q, J = 8 Hz), 2.09-2.20 (5H, m), 3.63 (4H, s), 3.80-3.90 (4H, m), 4.08 (2H, t, J = 6 Hz), 4.36 (1H, d, J = 13 Hz), 4. 79 (1H, d, J = 13 Hz), 6.78-6.88 (2H, m), 6.89 (1H, d, J = 5 Hz), 7.36-7.46 (2H, m), 8.26 (1H, d, J = 5 Hz). Example 5 Sodium salt of 2- (((3-methyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-i1) methoxy) pyridin-2-yl) methyl sulfinyl) -lH-benzimidazole Formula 44 (5a) 2-oxopropyl benzoate Formula 45 To a solution of pyridine (25 ml) and THF (10 ml) of hydroxyacetone (5 g, 67.5 mmol), benzoyl chloride (12 ml, 103 mmol) was added dropwise at 0 ° C under a nitrogen atmosphere and the The mixture was stirred for 43 hours at room temperature. Ice was added to the reaction mixture, which was then diluted with ethyl acetate. The organic layer was washed with IN hydrochloric acid, water, and a saline solution, dried over anhydrous sodium sulfate, and concentrated. The crude product obtained was purified by column chromatography on silica gel (elution solvent: heptane / ethyl acetate gradient = l / 0-l / l). The desired fractions were concentrated to obtain the title compound (10.56 g, 87.8% yield) as a light yellow oil. X H NMR (400 MHz, DMSO-d 6) d ppm; 2.14 (3H, s), 5.01 (2H, s), 7.51-7.58 (2H, m), 7.65-7.70 (ÍH, m), 7.95-8.00 (2H, m). (5b) benzoate of (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methyl Formula 46 2-oxopropyl benzoate (4 g, 22.4 mmole) obtained in step (5a) was mixed with 1,3-dioxolan-2,2-diyldimethanol (3 g, 22.4 mmole) obtained in step (4c), triethyl orthoformate (3.8 ml, 22.8 mmole) , and p-toluenesulfonic acid monohydrate (200 mg, 1.05 mmol). The mixture was stirred at room temperature for 13.5 hours. To the mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added. The organic layer was washed with water twice and with a saline solution, dried over anhydrous sodium sulfate, and concentrated. The product crude obtained was purified by column chromatography on silica gel (elution solvent: heptane / ethyl acetate = l / 0-l / l gradient) and the desired fractions were concentrated to obtain the title compound (1.92 g, 29.1% yield) as a colorless oil. H NMR (400 MHz, DMSO-d6) d ppm; 1.41 (3H, s), 3.64-3.76 (4H, m), 3.80-3.88 (4H, m), 4.33 (2H, s), 7.50-7.57 (2H, m), 7.64-7.70 (ÍH, m), 7.92-8.00 (2H, m). (5c) (8-methyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8-ylmethanol Formula 47 To a THF solution (10 ml) and methanol (5 ml) of the benzoate of (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methyl (1.92 g, 6.52 mmol) obtained in Step (5b), an aqueous IN sodium hydroxide solution (10 ml, 10 mmol) was added and stirred at room temperature for one hour. The reaction mixture was extracted with dichloromethane (50 ml) four times, dried over anhydrous sodium sulfate, and then concentrated. The crude product obtained was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate = 1/1-l / 1) and the desired fractions were concentrated to obtain the title compound (1.12 g, 90.0% yield) as a white solid. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.24 (3H, s), 3.33 (2H, d, J = 6 Hz), 3.60 (4H, s), 3.80-3.85 (4H, m), 4.81 (1H, t, J = 6 Hz). (5d) 2,3-dimethyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridine-1-oxide Formula 48 To a solution of dimethyl sulfoxide (15 ml) of (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methanol (1.11 g, . 82 mmole) obtained in step (5c), sodium hydride was added, in oil (326 mg, 8.15 mmol according to the estimated content as 60%) at room temperature under a nitrogen atmosphere. The mixture was stirred for 30 minutes under the same conditions. To the reaction mixture, 4-chloro-2,3-dimethylpyridine 1-oxide (917 mg, 5.82 mmol) was added at room temperature and the reaction mixture was stirred at 70 ° C for 4.5 hours. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (elution solvent: acetate gradient). ethyl / methanol = 1 / 0-5 / 2) and the desired fractions were concentrated to obtain the title compound (1.20 g, 66.1% yield) as a brown oil. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.42 (3H, s), 2.12 (3H, s), 2.33 (3H, s), 3.65-3.75 (4H, m), 3.85 (4H, s), 4.07 (2H, s), 7.00 (1H, d, J = 7 Hz), 8.07 (1H, d, J = 7 Hz). (5e) (3-methyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-i1) methoxy) pyridin-2-yl) methanol Formula 49 The 2,3-dimethyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridine 1-oxide (1.20 g, 3.84 mmol) obtained in the Step (5d) was mixed with acetic anhydride (10 ml). To the mixture, triethylamine (0.8 ml, 5.74 mmol) was added and the mixture was stirred at 50 ° C for 2 hours. The reaction mixture was concentrated and methanol (10 ml) was added to the residue. Then a solution of 5N aqueous sodium hydroxide (7 ml) was added to the mixture, and it was stirred at room temperature for 30 minutes. A solution of saturated aqueous ammonium chloride (7 ml) was added to the resulting mixture and the pH was adjusted to about 10. The mixture The reaction medium was diluted with ethyl acetate, and the organic layer was washed with a 2N aqueous sodium hydroxide solution, water, and a saline solution, dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by column chromatography on silica gel (elution solvent: ethylacetate / methanol gradient = 1 / 0-4 / 1) and a desired fraction (s) was concentrated obtain the title compound (312 mg, 26.1% yield) as a light yellow solid. : H NMR (400 MHz, DMSO-d6) d ppm; 1.44 (3H, s), 2. 11 (3H, s), 3.65-3.75 (4H, m), 3.85 (4H, s), 4.08 (2H, s), 4.51 (2H, d, J = 5 Hz), 4.97 (1H, t, J = 5 Hz), 6.99 (1H, d, J = 6 Hz), 8.20 (HH, d, J = 6 Hz). (5f) 2- (((3-methyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridin-2-yl) methyl) thio) -1H-benzimidazole Formula 50 To a THF solution (7 mL) of (3-methyl-4- ((8-methyl-1,, 7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridin-2-yl) methanol ( 312 mg, 1.00 mmol) obtained in step (5e), triethylamine (0.30 ml, 2.15 mmol) was added at temperature environment, and then methanesulfonyl chloride (0.12 ml, 1.55 mmol) was added under cooling in a salt-ice bath and stirred for 30 minutes under the same conditions. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and a saline solution, dried over anhydrous sodium sulfate, and concentrated. The residue obtained was dissolved in ethanol (6 ml). To the resulting solution, 2-mercaptobenzimidazole was added (150 mg, 1.00 mmol) and sodium hydroxide (160 mg, 4.00 mmol) and stirred at room temperature for 16.5 hours. After the reaction mixture was concentrated, NH silica gel was added to the residue and the mixture was dried. The crude product obtained was purified by column chromatography on silica gel (elution solvent: heptane / ethyl acetate gradient = 1 / 0.1-0 / 1) and the desired fractions were concentrated to obtain the title compound (377 mg, 85.0% yield) as a white foam. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.43 (3H, s), 2. 21 (3H, s), 3.66-3.76 (4H, m), 3.85 (4H, s), 4.09 (2H, s), 4.68 (2H, s), 7.02 (1H, d, J = 6 Hz), 7.07 -7.14 (2H, m), 7.37-7.50 (2H, m), 8.22 (1H, d, J = 6 Hz), 12.59 (1H, br s). (5g) 2- (((3-methyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridin-2- il) methyl) sulfinyl) -lH-benzimidazole Formula 51 To a solution of toluene (8.1 ml) and methanol (0.9 ml) of 2- (((3-methyl-4- ((8-methyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8-il ) methoxy) pyridin-2-yl) methyl) thio) -1H-benzimidazole (372 mg, 0.84 mmol) obtained in step (5f), a toluene solution (2.7 ml) and methanol were added dropwise (0.3 ml) of 3-chlorobenzoic acid (200 mg, 0.76 mmol according to the estimated content as 65%) from -55 ° C to -50 ° C for 10 minutes in a nitrogen atmosphere. The mixture was stirred at -60 ° C to -50 ° C for 1.5 hours. The reaction was terminated by the addition of 12 ml of a saturated aqueous solution of sodium hydrogen carbonate at the same temperature. The mixture was extracted with 50 ml of chloroform twice, and then, the organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product obtained was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / methanol gradient = 1 / 0-4 / 1) and the desired fractions were concentrated. The white foam obtained was re-precipitated with chloroform and ether diethyl and filtered. The operation was repeated twice to obtain the title compound (148 mg, 38.4% yield) as a white solid. 1 R NMR (400 MHz, DMSO-d 6) d ppm; 1.43 (3H, s), 2.14 (3H, s), 3.65-3.77 (4H, m), 3.85 (4H, s), 4.09 (2H, s), 4.69 (1H, d, J = 14 Hz), 4.78 (1H, d, J = 14 Hz), 7.02 (1H, d, J = 6 Hz), 7.20-7.32 (2H, m), 7.53-7.70 (2H, m), 8.20 (1H, d, J = 6 Hz). (5h) Sodium salt of 2- (((3-methyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 52 To a solution of ethanol (4 ml) solution of 2 - (((3-methyl-4- ((8-methyl-1, 4,7, 9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridine 2-yl) methyl) sulfinyl) -lH-benzimidazole (147 mg, 0.32 mmol) obtained in step (5g), a solution of IN aqueous sodium hydroxide (320 [mu] l, 0.32 mmol) was added at room temperature environment and stirred for 10 minutes and then the mixture was concentrated. Methanol was added to the residue and concentrated. After this operation was repeated twice, ethyl ether was added and the suspension obtained was let it rest. After the supernatant was discarded, the residue was dried by a vacuum pump to obtain the title compound (147 mg, 95.4% yield) as a white solid. : H NMR (400 MHz, DMSO-d6) d ppm; 1.43 (3H, s), 2.18 (3H, s), 3.66-3.76 (4H, m), 3.85 (4H, s), 4.07 (2H, s), 4.36 (1H, d, J = 13 Hz), 4.81 (1H, d, J = 13 Hz), 6.78-6.88 (2H, m), 6.99 (1H, d, J = 6 Hz), 7.38-7.46 (2H, m), 8.27 (1H, d, J = 6 Hz). EXAMPLE 6 Sodium salt of 2- (((4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 53 (6a) (2-methoxy-l, 3-dioxan-5-yl) methanol Formula 54 A mixture of 2- (hydroxymethyl) -1,3-propanediol (1.7 g, 16 mmol), trimethyl orthoformate (7 ml, 64.1 mmol), and p-Toluenesulfonic acid monohydrate (275 mg, 1.6 mmol) was stirred at room temperature for 22 hours. To the reaction mixture, triethylamine (447 [mu] l) was added and the mixture was concentrated. The residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate) to obtain the title compound (1.4 g, 59.1% yield), which is a cis and trans mixture (1: 1). ), as a light yellow oil. 1 H NMR (400 MHz, CDC13) d ppm; 1.85-1.92 (0.5H, m), 1.93-2.04 (0.5H, m), 3.34 (1.5H, s), 3.41 (1.5H, s), 3.62-3.84 (3H, m), 3.90 (1H, dd , J = 4, 12 Hz), 4.03 (1H, dd, J = 6, 12 Hz), 4.27 (1H, dd, J = 4, 12 Hz), 5.22 (0.5H, s), 5.25 (0.5H, s). (6b) 4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) -2,3-dimethylpyridine 1-oxide of Formula 55 To a solution of dimethisulfoxide (10 ml) of (2-methoxy-1,3-dioxan-5-yl) methanol (2.0 g, 13.5 mmol) obtained in the same manner as step (6a), sodium hydride was added. , in oil (770 mg, 14.9 mmol according to the estimated content as 55%) at room temperature. To the mixture, it added 1-oxide of 4-chloro-2,3-dimethylpyridine (2.13 g, 13.5 mmol) and the mixture was stirred at 60 ° C for 2.5 hours. After cooling the reaction mixture at room temperature, it was concentrated. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / methanol) to obtain the title compound (1.8 g, 49.5% yield), which is a cis-like mixture. trans (1: 1), as a yellow oil. 1R NMR (400 MHz, CDC13) d ppm; 2.12-2.30 (ÍH, m), 2.20 (3H, s), 2.54 (3H, s), 3.41 (1.5H, s), 3.45 (1.5H, s), 3.77 (ÍH, dd, J = 4, 12 Hz), 4.01 (1H, dd, J = 4, 12 Hz), 4.08-4.26 (3H, m), 4.39 (1H, dd, J = 4, 12 Hz), 5.28 (0.5H, s), 5.29 (0.5H, s), 6. 65 (0.5H, d, J = 8 Hz), 6.69 (0.5H, d, J = 8 Hz), 8.15 (0.5H, d, j = 8 Hz), 8.16 (0.5H, d, J = 8 Hz ). (6c) (4- ((2-methoxy-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol Formula 56 The 1-oxide of 4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) -2,3-dimethylpyridine (1.8 g, 6.68 ml) obtained in step (6b) was mixed with acetic anhydride (8 ml). The mixture was stirred at 100 ° C for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. To the residue, methanol (10 ml) and 5N of aqueous sodium hydroxide solution (5 ml) were added and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated and the residue was separated with a saturated saline solution and ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated and the residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate, ethyl acetate / methanol) to obtain the compound of the title (0.41 g, yield: 22.8%), which is a cis and trans (1: 1) mixture, as a yellow oil. 1 H NMR (400 MHz, CDC13) d ppm; 2.04 (3H, s), 2.12-2.22 (0.5H, m), 2.24-2.32 (0.5H, m), 3.41 (1.5H, s), 3.44 (1.5H, s), 3.79 (1H, dd, J = 4, 12 Hz), 4.01 (1H, dd, J = 4, 12 Hz), 4.10-4.20 (2H, m), 4.23 (1H, d, J = 8 Hz), 4.38 (1H, dd, J = 4, 12 Hz), 4.66 (2H, s), 4.86 (1H, br s), 5.28 (0.5H, s), 5.29 (0.5H, s), 6.73 (0.5H, d, J = 8 Hz), 6.76 (0.5H, d, J = 8 Hz), 8.31 (0.5H, d, J = 8 Hz), 8.32 (0.5H, d, J = 8 Hz). (6d) 2- (((4- ((2-methoxy-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 57 To a solution of tetrahydrofuran (dehydrated) (10 ml) of (4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol (0.41 g, 1.52 mmole) obtained in step (6c) and triethylamine (1.06 ml, 7.61 mmol), methanesulfonyl chloride (176 μl, 2.27 mmol) was added dropwise under cooling with ice cooling under a nitrogen atmosphere. The mixture was stirred for 1.5 hours under the same conditions. To the mix, 2-mercaptobenzimidazole (228 mg, 1.52 mmol) was added and stirred at room temperature for 20 hours. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate) to obtain the title compound (324 mg, 53.1% yield), which is a cis and trans mixture (1: 1) , like a light yellow foam. H NMR (400 MHz, CDC13) d ppm; 2.12-2.24 (ÍH, m), 2. 27 (3H, s), 3.4K1.5H, s), 3.44 (1.5H, s), 3.79 (1H, dd, J = 4, 12 Hz), 4.02 (1H, dd, J = 4, 12 Hz) , 4.12-4.20 (2H, m), 4.27 (1H, d, J = 8 Hz), 4.38 (2H, s), 4.36-4.44 (ÍH, m), 5.27 (0.5H, s), 5.29 (0.5H, s), 6.78 (0.5H, d, J = 8 Hz), 6.82 (0.5H, d, J = 8 Hz), 7.15-7.24 (2H, m), 7. 3-7.50 (HH, m), 7.58-7.67 (HH, m), 8.35-8.44 (HH) , m). (6e) 2- (((4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 58 To a toluene / methanol (10: 1) solution (20 ml) of 2- (((4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) ) methyl) thio) -lH-benzimidazole (324 mg, 807 μmol) obtained in step (6d), a solution of toluene / methanol (10: 1) (5 ml) of 3-chlorobenzoic acid was added dropwise. (193 mg, 726 μmoles according to the estimated content as 65%) of -50 ° C to -60 ° C for 5 minutes in a nitrogen atmosphere. The mixture was stirred for 2 hours under the same conditions. To the reaction mixture, a saturated aqueous solution of sodium acid carbonate was added and the resulting mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate). ethyl / methanol) to obtain the title compound (222 mg, 65.9% yield), which is a cis and trans (1: 1) mixture, as a light yellow foam. MS m / e (ESI) 418 (MH) +, 440 (MNa) + (6f) Sodium salt of 2- (((4- ((2-methoxy-1,3-dioxan-5-yl) methoxy) 3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 59 To a solution of ethanol (10 ml) of 2 - (((4 - ((2-methoxy-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH -benzimidazole (222 mg, 532 μmol) obtained in step (6e), a solution of IN aqueous sodium hydroxide (532 μl, 532 μmol) was added at room temperature and stirred for one hour. The mixture was concentrated and the residue was dissolved in ethanol. Then, ethyl ether was added to the mixture and the mixture was treated ultrasonically. The resulting solid was collected through filtration in a nitrogen atmosphere. The solid was dried under reduced pressure to obtain the title compound (234 mg, yield: 83.4%), which is a cis and trans (1: 1) mixture, as a light yellow solid.

X H NMR (400 MHz, DMSO-d 6) d ppm; 2.14-2.21 (ÍH, m), 2.18 (3H, s), 3.27 (1.5H, s), 3.28 (1.5H, s), 3.66-3.76 (ÍH, m), 3.88-4.04 (2H, m), 4.09 (2H, dd, J = 4, 12 Hz), 4.16-4.23 (HH, m), 4.35 (1H, d, J = 13 Hz), 4.82 (1H, d, J = 13 Hz), 5.24 (0.5 H, s), 5.27 (0.5H, s), 6.83 (2H, dd, J = 3, 6 Hz), 6.93 (1H, d, J = 6 Hz), 7.41 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz). [0371] MS m / e (ESI) 440 (MNa) + EXAMPLE 7 Sodium salt of 2- (((4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy ) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 60 (7a) Methanol Formula 61 A mixture of 2- (hydroxymethyl) -1,3-propanediol (2.2 g, 20.7 mmol), 1,3-difluoroacetone (3.89 g, 41.4 mmol), trimethyl orthoformate (3.44 ml, 20.7 mmol), and p-toluenesulfonic acid monohydrate (356 mg, 2.07 mmol) was stirred 60 ° C for 10 hours. After completing the reaction, triethylamine (577 μl) was added to the reaction mixture, which was then concentrated. The residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate) to obtain the title compound (1.6 g, yield: 43.4%) as a light yellow oil. XH NMR (400 MHz, CDC13) d ppm; 1.97-2.10 (ÍH, m), 3.72-3.82 (2H, m), 3.87 (2H, dd, J = 4, 12 Hz), 4.10 (2H, dd, J = 4, 12 Hz), 4.46 (2H, dd, J = 2, 48 Hz), 4.57 (2H, dd, J = 2, 48 Hz). (7b) 4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -2, 3-dimethylpyridine-1-oxide Formula 62 To a solution of dimethylsulfoxide (10 ml) of (2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methanol (1.6 g, 8.98 mmol) obtained in step (7a) was added hydride. sodium, in oil (431 mg, 9.88 mmoles according to the estimated content as 55%) at room temperature. To the mixture, 1-oxide of 4-chloro-2,3-dimethylpyridine (1.42 g, 8.98 mmol) was added and the mixture was stirred at 60 ° C for 2 hours. After cooling the reaction mixture at room temperature, it was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting solvent: ethyl acetate / methanol) to obtain the title compound (1.63 g, yield: 60.6%) as a yellow oil. XH NMR (400 MHz, CDC13) d ppm; 2.19 (3H, s), 2.26- 2.36 (1H, m), 2.54 (3H, s), 3.99 (2H, dd, J = 4, 12 Hz), 4.13 (2H, d, J = 8 Hz), 4.21 (2H, dd, J = 4, 12 Hz), 4.45 (2H, dd, J = 2, 48 Hz), 4.62 (2H, dd, J = 2, 48 Hz), 6.64 (1H, d, J = 8 Hz), 8.14 (1H, d, J = 8 Hz). (7c) (4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol Formula 63 The 1-oxide of 4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -2,3-dimethylpyridine (1.63 g, 5.37 mmol) obtained in step (7b) it was mixed with acetic anhydride (8 ml). The mixture was stirred at 100 ° C for 2 hours, cooled to room temperature, and then, concentrated under reduced pressure. To the residue, methanol (10 ml) and 5N of aqueous sodium hydroxide solution (5 ml) were added and the mixture was stirred at room temperature for 3 hours. The mixture of The reaction was concentrated and the residue was separated between saturated saline and ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated and the residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate, ethyl acetate / methanol) to obtain the compound of the title (385 mg, yield 23.6%) as a yellow oil. 1 NMR (400 MHz, CDC13) d ppm; 2.04 (3H, s), 2.32-2.40 (1H, m), 4.01 (2H, dd, J = 4, 12 Hz), 4.16 (2H, d, J = 8 Hz), 4.21 (2H, dd, J = 4, 12 Hz), 4.48 (2H, dd, J = 2, 48 Hz), 4.62 (2H, dd, J = 2, 48 Hz), 4.66 (2H, s), 4.84 (1H, br s), 6.73 (1H, d, J = 8 Hz), 8.31 (ÍH, d, J = 8 Hz). (7d) 2- (((4- ((2, 2-bis (fluoromethyl) -1, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 64 To a tetrahydrofuran (dehydrated) solution (20 ml) of (4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol (385 g) mg, 1.27 mmol) obtained in step (7c) and triethylamine (885 μl, 6.35 mmol), methanesulfonyl chloride (177 μl, 2.29 mmol) was added dropwise under cooling with ice cooling in an atmosphere of nitrogen. The mixture was stirred for 1.0 hours under the same conditions. To the reaction mixture, 2-mercaptobenzimidazole (191 mg, 1.27 mmol) was added and stirred at room temperature for 10 hours. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate) to obtain the title compound (305 mg, yield: 55.1%) as a light yellow foam. H NMR (400 MHz, CDC13) d ppm; 2.26 (3H, s), 2.30-2.38 (1H, m), 4.01 (2H, dd, J = 4, 12 Hz), 4.18 (2H, d, J = 8 Hz), 4.22 (2H, dd, J = 4, 12 Hz), 4.38 (2H, s), 4.46 (2H, dd, J = 2, 48 Hz), 4.62 (2H, dd, J = 2, 48 Hz), 6.79 (1H, d, J = 8 Hz), 7.15-7.23 (2H, m), 7.42-7.50 (HH, m), 7.56-7.66 (HH, m), 8.37 (1H, d, J = 8 Hz). (7e) 2- (((4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 65 To a toluene / methanol (10: 1) solution (20 ml) of 2- (((4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -3-methylpyridin -2-yl) methyl) thio) -lH-benzimidazole (305 mg, 700 mmol) obtained in step (7d), a solution of toluene / methanol (10: 1) (5 ml) of 3-fold acid was added dropwise. -chloroberbenzoic (167 mg, 630 μmoles according to the estimated content as 65%) from -50 ° C to -60 ° C for 5 minutes in a nitrogen atmosphere. The mixture was stirred for 2 hours under the same conditions. To the reaction mixture, a saturated aqueous solution of sodium acid carbonate was added and the resulting mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / methanol) to obtain the title compound (215 mg, yield: 68%) as a light yellow foam. MS m / e (ESI) 452 (MH) +, 474 (MNa) + (7f) Na salt of 2- (((4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5 -yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) - lH-benzimidazole Formula 66 To a solution of ethanol (10 mL) of 2- (((4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl sulfinyl) -lH-benzimidazole (215 mg, 476 μmol) obtained in step (7e), an aqueous sodium hydroxide IN solution (476 μl, 476 μmol) was added at room temperature and stirred for one hour. After the mixture was concentrated and the residue was dissolved in ethanol, ethyl ether was added to the mixture. The mixture was treated ultrasonically and the resulting solid was collected through filtration in a nitrogen atmosphere. The solid was dried under reduced pressure to obtain the title compound (193 mg, yield: 85.6%) as a light yellow solid. X H NMR (400 MHz, DMS0-d 6) d ppm; 2.17 (3H, s), 2.18-2.28 (1H, m), 3.84-3.94 (2H, m), 4.06-4.18 (2H, m), 4.12 (2H, d, J = 8 Hz), 4.37 (1H, d, J = 12 Hz), 4.50 (2H, d, J = 47 Hz), 4.58 (2H, d, J = 47 Hz), 4.81 (1H, d, J = 12 Hz), 6.80-6.90 (2H, m), 6.94 (1H, d, J = 8 Hz), 7.38-7.48 (2H, m), 8.27 (1H, d, J = 8 Hz).

EXAMPLE 8 Sodium salt of 2- (((3-methyl-4- (2- (2-propyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -1 H- Benzimidazole Formula 67 (8a) (2-propyl-l, 3-dioxan-2-yl) ethyl acetate Formula 68 A mixture of ethyl 3-oxohexanoate (5 g, 31. 6 mmol), 1,3-propanediol (3.61 g, 47.4 mmol), trimethyl orthoformate (5.78 ml, 34.8 mmol), and p-toluenesulfonic acid monohydrate (272 mg, 1.58 mmol) was stirred at room temperature for 22 hours. After completing the reaction, triethylamine (881 μl, 6.32 mmol) was added to the reaction mixture which was then concentrated. The residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate) to obtain the title compound (5.5 g, yield: 80.5%) as a light yellow oil.

H NMR (400 MHz, CDC13) d ppm; 0.94 (3H, t, J = 7 Hz), 1.27 (3H, t, J = 7 Hz), 1.40-1.54 (2H, m), 1.55-1.68 (2H, m), 1.74-1.90 (2H, m) , 2.82 (2H, s), 3.87-4.06 (4H, m), 4.15 (2H, q, J = 7 Hz). 2- (2-propyl-l, 3-dioxan-2-yl) ethanol Formula 69 To a tetrahydrofuran (dehydrated) solution (30 ml) of ethyl (2-propyl-1, 3-dioxan-2-yl) acetate (5.5 g, 25.4 mmol) obtained in step (8a), lithium hydride was added. aluminum (578 mg, 15.2 mmol) in portions under cooling with ice cooling and stirred for one hour under cooling with ice. To the reaction mixture, water (0.6 ml), 2N of aqueous sodium hydroxide solution (0.6 ml), and water (1.8 ml) were added sequentially and the contents were filtered through celite. The filtrate was concentrated under reduced pressure to obtain the title compound (4.4 g, 99.4% yield), which was a crude product, as a light yellow oil. XH NMR (400 MHz, CDC13) d ppm; 0.97 (3H, t, J = 7 Hz), 1.22-1.42 (4H, m), x.82-2.00 (4H, m), 3.78-3.96 (4H, m), 3.96-4.08 (2H, m). (8c) 2-3-dimethyl-4- (2- (2-propyl-1, 3-1-oxide dioxan-2-yl) ethoxy) pyridine Formula 70 To a dimethylsulfoxide solution (20 ml) of (2- (2-propyl-1,3-dioxan-2-yl) ethanol (4.4 g, 25.3 mmol) obtained in step (8b), sodium hydride was added, oil (1.1 g, 25.3 mmol according to the estimated content as 55%) at room temperature To the mixture, 1-chloro-2,3-dimethylpyridine oxide (3.19 g, 20.2 mmol) was added and the mixture was stirred at 60 C for 1.5 hours After cooling to room temperature, the mixture was concentrated under reduced pressure.The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: heptane / ethyl acetate, acetate ethyl / methanol) to obtain the title compound (3.9 g, yield: 52.2%) as a light yellow oil.1H NMR (400 MHz, CDC13) d ppm 0.96 (3H, t, J = 7 Hz), 1.34 -1.48 (2H, m), 1.76-1.88 (2H, m), 2.14-2.26 (4H, m), 2.54 (3H, s), 2.62 (3H, s), 3.82-3.90 (2H, m), 3.92 -4.04 (2H, m), 4.17 (2H, t, J = 7 Hz), 6.69 (1H, d, J = 8 Hz), 8.14 (1H, d, J = 8 Hz). (8d) (3-Methyl-4- (2- (2-propyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methanol Formula 71 The 2,3-dimethyl-4- (2- (2-propyl-1, 3-dioxan-2-yl) ethoxy) pyridine 1-oxide (3.9 g, 13.2 mmol) obtained in step (8c) was mixed with acetic anhydride (16 ml). The mixture was stirred at 90 ° C for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. To the residue, methanol (20 ml) and 5N aqueous sodium hydroxide solution (10 ml) were added and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and the residue was separated by the use of a saturated saline solution and ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and the residue was purified by column chromatography on silica gel (eluting solvent: heptane / ethyl acetate, ethyl acetate / methanol) to obtain the compound of the title (1.69 g, yield: 43.3%) as a yellow oil. XH NMR (400 MHz, CDC13) d ppm; 0.96 (3H, t, J = 7 Hz), 1. 35-1.48 (2H, m), 1.52-1.66 (2H, m), 1.72-1.88 (2H, m), 2.03 (3H, s), 2.22 (2H, t, J = 7 Hz), 3.82-4.04 ( 4H, m), 4.19 (2H, t, J = 7 Hz), 4.65 (2H, s), 6.77 (1H, d, J = 8 Hz), 8.29 (1H, d, J = 8 Hz). (8e) 2- (((3-Methyl-4- (2- (2-propyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 72 To a solution of tetrahydrofuran (dehydrated) (30 ml) of (3-methyl-4- (2- (2-propyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methanol (445 ml , 1.51 mmole) obtained in step (8d) and triethylamine (1.05 ml, 7.55 mmole), methanesulfonyl chloride (210 μl, 2.72 mmole) was added dropwise under cooling with ice cooling under a nitrogen atmosphere and the mixture was stirred. He stirred for an hour under the same conditions. To the reaction mixture, 2-mercaptobenzimidazole (227 mg, 1.51 mmol) was added and stirred at room temperature for 3 days. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by chromatography of column on silica gel (elution solvent: heptane / ethyl acetate, ethyl acetate / methanol) to obtain the title compound (417 mg, yield: 64.6%) as a light yellow foam. H NMR (400 MHz, CDC13) d ppm; 0.96 (3H, t, J = 7 Hz), 1.35-1.47 (2H, m), 1.76-1.88 (4H, m), 2.22 (2H, t, J = 7 Hz), 2.25 (3H, s), 3.82 -3.91 (2H, m), 3.92-4.00 (2H, m), 4.22 (2H, t, J = 7 Hz), 4.37 (2H, s), 6.82 (1H, d, J = 8 Hz), 7.14- 7.24 (2H, m), 7.50-7.62 (2H, m), 8.35 (1H, d, J = 8 Hz). (8f) 2- (((3-Methyl-4- (2- (2-propyl-l, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 73 To a toluene-methanol (10: 1) solution (30 ml) of 2- (((3-methyl-4- (2- (2-propyl-l, 3-dioxan-2-yl) ethoxy) pyridin-2 -yl) methyl) thio) -lH-benzimidazole (417 mg, 975 μmol) obtained in step (8e), a solution of toluene / methanol (10: 1) (5 ml) of 3-chlorobenzoic acid was added dropwise. (233 mg, 878 μmoles according to the estimated content as 65%) at a temperature of -50 ° C to -60 ° C for 5 minutes in an atmosphere of nitrogen. The reaction mixture was stirred for 2 hours under the same conditions. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution was added, which was extracted with ethyl acetate. After the organic layer was concentrated, the residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / methanol) to obtain the title compound (311 mg, yield: 71.9%) , like a light yellow foam. ? H NMR (400 MHz, CDC13) d ppm; 0.95 (3H, t, J = 7 Hz), 1. 34-1.47 (2H, m), 1.70-1.88 (4H, m), 2.17 (3H, s), 2.20 (2H, t, J = 7 Hz), 3.82-3.92 (2H, m), 3.92-4.00 ( 2H, m), 4.17 (2H, t, J = 7 Hz), 4.65 (1H, d, J = 14 Hz), 4.82 (1H, d, J = 14 Hz), 6.78 (1H, d, J = 8 Hz), 7.28-7.38 (2H, m), 7.30-7.62 (2H, m), 8.30 (1H, d, J = 8 Hz). (8g) 2- (((3-Methyl-4- (2- (2-propyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -1 H sodium salt -benzimidazole Formula 74 To a solution of ethanol (6 ml) of 2- (((3-methyl-4- (2- (2-propy1-1, 3-dioxan-2-yl) ethoxy) pyridin-2- ilchmethyl) sulfinyl) -lH-benzimidazole (311 mg, 701 μmol) obtained in step (8f), an aqueous solution of IN sodium hydroxide (701 μl, 701 μmol) was added at room temperature and stirred for one hour . The mixture was concentrated and the residue was dissolved in ethanol. After ethyl ether was added to the solution, the solution was treated ultrasonically. The generated solid was collected through filtration under a nitrogen atmosphere, and the solid was dried under reduced pressure to obtain the title compound (283 mg, yield: 86.7%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d ppm; 0.87 (3H, t, J = 7 Hz), 1.26-1.38 (2H, m), 1.48-1.64 (2H, m), 1.67-1.74 (2H, m), 2.12-2.20 (2H, m), 2.16 ( 3H, s), 3.81 (4H, t, J = 7 Hz), 4.07 (2H, t, J = 7 Hz), 4.38 (1H, d, J = 13 Hz), 4.79 (1H, d, J = 13 Hz), 6.82-6.90 (2H, m), 6.91 (1H, d, J = 8 Hz), 7.36-7.50 (2H, m), 8.25 (1H, d, J = 8 Hz). MS m / e (ESI) 466 (MNa) +. EXAMPLE 9 Sodium salt of 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 75 Na (9a) 2, 2-dimethyl-l, 3-dioxan-5-ol Formula 76 To a solution of diethyl ether (150 ml) of 2,2-dimethyl-1,3-dioxan-5-one (15 g, 0.115 mol), lithium aluminum hydride (4.38 g, 0.115 mol) of 0 was added. at 8 ° C for one hour in a nitrogen atmosphere. To the reaction mixture was added sequentially, water (4.2 ml), 5N of aqueous sodium hydroxide solution (4.2 ml), and water (12.8 ml) by dripping from 0 to 10 ° C. The mixture was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound (14.2 g, 93.4%) as a colorless oil. XH NMR (400 MHz, CDC13) d ppm; 1.44 (3H, s), 1.46 (3H, s), 2.75-2.95 (lH, br), 3.51-3.55 (HH, m), 3.74-3.79 (2H, m), 4.05-4.10 (2H, m). (9b) 5- (benzyloxy) -2, 2-dimetheyl-l, 3-dioxane Formula 77 To a solution of N, N-dimethylformamide (200 ml) of 2, 2-dimethyl-l, 3-dioxan-5-ol (7.1 g, 0.054 mol) obtained in step (9a), sodium hydride was added, in oil (2.81 g, 0.064 moles according to the estimated content as 55 %) at 0 ° C and stirred. After adding benzyl bromide (12.9 ml, 0.108 mole) tetrabutylammonium iodide (220 mg, 0.001 mole) at the same temperature to the mixture, the mixture was stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate three times. The organic layers were combined, washed five times with water and eleven times with a saturated saline solution, dried over anhydrous sodium sulfate, and filtered. After NH silica gel was added, the resulting mixture was concentrated and purified by column chromatography on silica gel (elution solvent: heptane, heptane / ethyl acetate = 9/1, 4/1, ethyl acetate) to obtain the title compound (6.5 g, 54.5%) as a colorless oil. H NMR (400 MHz, CDC13) d ppm; 1.40 (3H, s), 1.45 (3H, s), 3.50-3.56 (lH, m), 3.77 (2H, dd, J = 7, 12 Hz), 3.95 (2H, dd, J = 4, 12 Hz) , 4.58 (2H, s), 7.28-7.38 (5H, m). (9c) 2- (benzyloxy) propan-1,3-diol Formula 78 To a methanol solution (50 ml) of 5- (benzyloxy) -2,2-dimethyl-1,3-dioxane (6.5 g, 29.2 mmol) obtained in step (9b), DOWEX (R) 50W-X8 was added. (5 g) and stirred at room temperature. After 2 hours, the reaction mixture was filtered and concentrated to obtain the title compound (5.0 g, 93.8%) as a colorless oil. ? NMR (400 MHz, CDC13) d ppm; 3.60-3.65 (ÍH, m), 3.74 (2H, dd, J = 5, 12 Hz), 3.82 (2H, dd, J = 4, 12 Hz), 4.67 (2H, s), 7.29-7.40 (5H, m). (9d) 7- (benzyloxy) -5, 9-dioxaspiro [3.5] nonane Formula 79 To a round bottom flask containing a benzene solution (50 ml) of 2- (benzyloxy) propane-1,3-diol (5.0 g, 27.4 mmol) obtained in step (9c), cyclobutanone (2.33 ml, 30.6 mmol), and p-toluenesulfonic acid monohydrate (100 mg, 0.53 mmol), a reflux cooling tube fitted with a water separator was attached Dean-Stark The mixture was under reflux for 2 hours. To the resulting mixture, triethylamine (0.4 ml, 0.72 mmol) was added and the mixture was concentrated to obtain the crude product. The crude product was purified by column chromatography on silica gel (NH silica gel, eluting solvent: heptane, heptane / ethyl acetate = 5/1) to obtain the title compound (6.3 g, yield: 98.2%) as a light yellow oil. XH NMR (400 MHz, CDC13) d ppm; 1.70-1.79 (2H, m), 2.20-2.29 (4H, m), 3.44-3.50 (ÍH, m), 3.64-3.69 (2H, m), 3.92 (2H, dd, J = 4, 12 Hz), 4.58 (2H, s), 7.27-7.39 (5H, m). (9e) 5, 9-dioxaspiro [3.5] nonan-7-ol Formula 80 To a solution of methanol (269 ml) of 7- (benzyloxy) -5,9-dioxaspiro [3.5] nonane (6.3 g, 26.9 mmol) obtained in step (9d), 20% palladium hydroxide (630 mg) was added. ) and stirred for 13 hours in a hydrogen atmosphere. The reaction vessel was purged with nitrogen and the insoluble matter was removed by filtration. The filtrate was concentrated to obtain a crude product. The crude product was purified by column chromatography on silica gel (NH silica gel, eluting solvent: heptane, heptane / ethyl acetate = 5/1) to obtain the title compound (3.42 g, yield: 88.2%) as a colorless oil. * H NMR (400 MHz, CDC13) d ppm; 1.72-1.82 (2H, m), 2.21-2.3K4H, m), 2.71-2.88 (HH, br), 3.50-3.56 (HH, m), 3.71-3.76 (2H, m), 3.93-3.98 (2H, m). (9f) 4- (5,9-dioxaspiro [3.5] non-7-yloxy) -2, 3-dimethylpyridine-1-oxide Formula 81 To a dimethylformamide solution (30 ml) of 5,9-dioxaspiro [3.5] nonan-7-ol (1.68 g, 11.7 mmol) obtained in step (9e), sodium hydride was added, in oil (587 mg, 13.5 mmoles according to the estimated content as 55%) at room temperature. The mixture was stirred at room temperature for 50 minutes. Then 1-chloro-2,3-dimethylpyridine oxide (1.84 g, 11.7 mmol) was added thereto, the mixture was stirred at 80 ° C for 2 hours. The reaction mixture was concentrated and dimethisulfoxide (30 ml) was added thereto and stirred 80 ° C. After 12 hours, sodium hydride, in oil (587 mg, 13.5 mmol according to the estimated 55% content) was added to the reaction mixture and stirred at 80 ° C. After one hour, the reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate, ethyl acetate / methanol = 9/1) to obtain the compound of the title (2.00 g, yield: 64.4%) as a light yellow oil. * H NMR (400 MHz, CDC13) d ppm; 1.76-1.82 (2H, m), 2. 24 (3H, s), 2.27-2.32 (4H, m), 2.54 (3H, s), 3.85 (2H, dd, J = 6, 12 Hz), 4.07 (2H, dd, J = 3, 12 Hz) , 4.24-4.30 (HH, m), 6.62 (1H, d, J = 7 Hz), 8.16 (1H, d, J = 7 Hz). (9g) (4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methanol Formula 82 The 1-oxide of 4- (5,9-dioxaspiro [3.5] non-7-yloxy) -2,3-dimethylpyridine (1.25 g, 4.71 mmol) obtained in step (9f) was mixed with acetic anhydride (4.45 ml, 47.1 mmol). Then the mixture was stirred at room temperature by a hour, it was cooled to 0 ° C. After triethylamine (656 μl, 4.71 mmol) was added, the mixture was stirred for one hour and stirred at room temperature for another hour. After stirring 50 ° C for 2 hours, the reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / heptane = 1/3). To the obtained product, methanol (30 ml) and 5N of aqueous sodium hydroxide solution (2.24 ml, 11.2 = moles) were added, and the reaction mixture was stirred at room temperature for one hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture to adjust the pH of the solution to about 9 and then concentrated. The resulting residue was extracted with ethyl acetate three times. The organic layers were combined, washed with a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (630 mg, yield: 49.6%) as a light yellow oil. XH NMR (400 MHz, CDC13) d ppm; 1.77-1.85 (2H, m), 2.08 (3H, s), 2.26-2.35 (4H, m), 3.85 (2H, dd, J = 6, 12 Hz), 4.11 (2H, dd, J = 4, 12 Hz), .38-4.44 (1H, m), 4.68 (2H, s), 6.72 (1H, d, J = 6 Hz), 8.31 (1H, d, J = 6 Hz). (9h) 2 - (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 83 A solution of tetrahydrofuran (20 ml) of (4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methanol (630 mg, 2.37 mmol) obtained in step (9g) ) and triethylamine (0.66 ml, 4.74 mmol) was stirred at -10 ° C. After 10 minutes, methanesulfonyl chloride (275 μL, 3.56 mmol) was added at the same temperature and the resulting mixture was stirred under the same conditions for 30 minutes. To the reaction mixture, a saturated aqueous solution of sodium acid carbonate was emptied. The reaction mixture was extracted with ethyl acetate twice and the organic layers were combined, washed with a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated. Dichloromethane (30 ml) was added to the residue to form a solution, and then 2-mercaptobenzimidazole (354 mg, 2.36 mmol) was added at room temperature. In addition, triethylamine (0.493 ml, 3.54 mmol) was added, and methanol was added further until the 2-mercaptobenzimidazole was dissolved. After the reaction mixture was stirred at room temperature for 2 hours, it was added NH silica gel to the reaction mixture, which was then concentrated. The residue was subjected to column chromatography on silica gel (elution solvent: heptane / ethyl acetate =: L / l, ethyl acetate) to obtain the title compound (690 mg, yield: 73.6%) as a solid White. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.61-1.70 (2H, m), 2. 13-2.25 (4H, m), 2.22 (3H, s), 3.77 (2H, dd, J = 4, 12 Hz), 4. 02 (2H, dd, J = 2, 12 Hz), 4.44-4.48 (HH, m), 4.68 (2H, s), 6.97 (1H, d, J = 6 Hz), 7.07-7.13 (2H, m) , 7.37-7.50 (2H, m), 8. 21 (ÍH, d, J = 6 Hz). (9i) 2 - (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 84 A solution of toluene (30 ml) / methanol (3 ml) of 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole (290 mg, 0.73 mmol) obtained in step (9h), a solution of toluene / methanol (10: 1) of 3-chlorobenzoic acid (174 mg, 0.65 mmol based on the estimated content as 65%) was added. ) at -70 ° C in an atmosphere of nitrogen. After the mixture was stirred at -50 ° C for one hour, a saturated aqueous solution of sodium acid carbonate was added. After the mixture was warmed to room temperature, the mixture was extracted with ethyl acetate twice. The organic layers were combined and dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate, ethyl acetate / methanol = 9/1). The fractions containing the title compound by the use of ethyl acetate and concentrated. After ethyl ether was added to the residue, the solvent was distilled off to obtain the title compound (230 mg, yield: 76.2%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.60-1.70 (2H, m), 2.15 (3H, s), 2.12-2.25 (4H, m), 3.73-3.81 (2H, m), 3.98-4.06 (2H, m), 4.44-4.49 (H, m) ), 4.70 (1H, d, J = 14 Hz), 4.78 (1H, d, J = 14 Hz), 6.97 (1H, d, J = 6 Hz), 7.25-7.32 (2H, m), 7.56-7.70 (2H, m), 8.19 (1H, d, J = 6 Hz). (9j) Sodium salt of 2 - (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 85 To a solution of ethanol (20 ml) of 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole ( 230 mg, 0.56 mmole) obtained in step (9i), an aqueous sodium hydroxide solution (0.56 ml, 0.56 mmole) was added at room temperature. The mixture was stirred for one hour and then concentrated. After the residue was subjected to azeotropic distillation with ethanol twice, suspended with diethyl ether, the resulting solid was collected through filtration and dried to obtain the title compound (190 mg, yield: 91%) as a white solid . X H NMR (400 MHz, DMSO-d 6) d ppm; 1.60-1.70 (2H, m), 2. 13-2.27 (4H, m), 2.22 (3H, s), 3.74-3.81 (2H, m), 3.99-4.06 (2H, m), 4.37 (1H, d, J = 13 Hz), 4.42-4.50 ( ÍH, m), 4. 85 (1H, d, J = 13 Hz), 6.82-6.88 (2H, m), 6.94 (1H, d, J = 6 Hz), 7. 40-7.46 (2H, m), 8.25 (1H, d, J = 6 Hz). Example 10 Sodium salt of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2- il) methyl) sulfinyl) -lH-benzimidazole Formula 86 Na (10a) 1,5, 9-trioxaspiro [5.5] undec-3-ylmethanol Formula 87 A mixture of 2- (hydroxymethyl) -1,3-propanediol (3.3 g, 31.1 mmol), tetrahydro-4H-pyran-4-one (3.12 g, 31.2 mmol), p-toluenesulfonic acid monohydrate (268 mg, 1.41 mmol) ) and benzene (68.3 ml) was brought to reflux in a round bottom flask with a cooling tube and Dean-Stark by 6 hours. After cooling to room temperature, triethylamine (1 ml) was added to the reaction mixture and the mixture was concentrated. The residue was purified by column chromatography on silica gel (silica gel: 200 g, eluting solvent: heptane, heptane / ethyl acetate = 1/1, 1/3) to obtain the title compound (3.80 g, yield: 64.9%) as a colorless oil.

X H NMR (400 MHz, DMSO-d 6) d ppm; 1.67-1.82 (5H, m), 3.35-3.42 (2H, m), 3.49-3.57 (4H, m), 3.65 (2H, dd, J = 7, 12 Hz), 3.86 (2H, dd, J = 4 , 12 Hz), 4.56 (1H, t, J = 5 Hz). (10b) 2,3-dimethyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridine 1-oxide Formula 88 To a dimethyl sulfoxide solution (30 ml) of 1,5,9-trioxaspiro [5.5] undec-3-ylmethanol (3.80 g, 20.2 mmol) obtained in step (10a), sodium hydride was added in oil (770 mg , 19.3 mmoles according to the content estimated as 60%) at room temperature. The mixture was stirred at room temperature for 30 minutes in a nitrogen atmosphere. To the mixture, 1-chloro-2,3-dimethylpyridine oxide (2.6 g, 16.5 mmol) was added, the mixture was stirred at 60 ° C for 2.5 hours. After room temperature was cooled, the reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (NH silica gel: 200 g, eluting solvent: heptane, heptane / ethyl acetate = 1 μl, 1/3, ethyl acetate, ethyl acetate / methanol = 10 / l) to obtain the title compound (3.38 g, yield: 66.2%) as a pale yellow gum. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.78 (2H, t, J = 5 Hz), 1. 85 (2H, t, J = 5 Hz), 2.07-2.20 (HH, m), 2.13 (3H, s), 2.35 (3H, s), 3.52-3.60 (4H, m), 3.80 (2H, dd, J = 6, 12 Hz), 4.04 (2H, dd, J = 4, 12 Hz), 4.11 (2H, d, J = 7 Hz), 6.97 (1H, d, J = 7 Hz), 8.08 (ÍH, d, J = 7 Hz). (10c) (3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methanol Formula 89 The 2,3-dimethyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridine 1-oxide (3.31 g, 10.7 mmol) obtained in step (10b) was mixed with acetic anhydride (30 ml, 331 mmol). The mixture was stirred at 85 ° C for 1 hour and 55 minutes. After cooling to room temperature, the reaction mixture was concentrated. To the residue, methanol (50 ml) and 5N of aqueous sodium hydroxide solution (30 ml, 150 mmol) were added and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated and the residue was partitioned between water and ethyl acetate. The organic layer was washed twice with a solution of IN aqueous sodium hydroxide, dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain the title compound (1.97 g, yield: 59.5%).

Brown color. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.78 (2H, t, J = 5 Hz), 1. 85 (2H, t, J = 5 Hz), 2.09-2.20 (ÍH, m), 2.12 (3H, s), 3.50- 3.62 (4H, m), 3.82 (2H, dd, J = 6, 12 Hz) , 4.05 (2H, dd, J = 4, 12 Hz), 4.14 (2H, d, J = 7 Hz), 4.53 (2H, d, J = 6 Hz), 4.99 (1H, t, J = 6 Hz), 6.97 (1H, d, J = 6 Hz), 8.24 (HH, d, J = 6 Hz). (lOd) 2- (((3-methyl-4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 90 To a dichloromethane (dehydrated) solution (20 ml) of (3-methyl-1,4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methanol (1.26 g), 4.07 mmol) obtained in step (10c) and triethylamine (1.13 ml, 8.14 mmol), methanesulfonyl chloride (473 μl, 6.11 mmol) was added by dripping from 1 ° C to 4 ° C for 20 minutes in an atmosphere of nitrogen. The mixture was stirred for 40 minutes under the same conditions. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, they filtered and concentrated. The residue was mixed with 2-mercaptobenzimidazole (595 mg, 3.96 mmol). The mixture was stirred in methanol (15 ml) at room temperature for 17 hours and 45 minutes. NH silica gel (10 g) was added to the reaction mixture and the mixture was concentrated. The residue was subjected to silica gel column chromatography (silica gel: 15 g, eluting solvent: heptane / ethyl acetate = 50/50, 25/75, ethyl acetate, ethyl acetate / methanol = 10 / l. ) to obtain a mixture of the title compound and 2-mercaptobenzimidazole. The mixture was further purified by column chromatography on silica gel (silica gel: 15 g, eluting solvent: heptane / ethyl acetate = 50/50, 25/75, ethyl acetate, ethyl acetate / methanol = 10 / l). The oil obtained was suspended in hexane, concentrated to obtain the title compound (994 mg, yield: 56.8%) as a colorless foam. X H NMR (400 MHz, DMSO-d 6) d ppm; 1.78 (2H, t, J = 5 Hz), 1.85 (2H, t, J = 5 Hz), 2.10-2.20 (HH, m), 2.22 (3H, s), 3.52-3.60 (4H, m), 3.82 (2H, dd, J = 6, 12 Hz), 4.05 (2H, dd, J = 4, 12 Hz), 4.15 (2H, d, J = 7 Hz), 4.70 (2H, s), 6.99 (1H, d, J = 6 Hz), 7.09-7.16 (2H, m), 7.38-7.53 (2H, br), 8.25 (1H, d, J = 6 Hz), 12.62 (1H, br s). (lOe) 2- (((3-meti1-4- (1,5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 91 To a solution of toluene (30 ml) -methanol (3 ml) of 2- (((3-methyl-4- (1,5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) thio) -lH-benzimidazole (974 mg, 2.21 mmol) obtained in step (10d), a solution of toluene (1 ml) -methanol (1 ml) of 3-chlorobenzoic acid (528 mg, 1.99 mmoles according to the estimated content as 65%) at -65 ° C for 5 minutes in a nitrogen atmosphere. The mixture was stirred for 55 minutes under the same conditions. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate was added. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (silica gel NH: 20 g, eluting solvent: dichloromethane, dichloromethane / methanol = 10 / l). The fractions containing the title compound were collected with ethyl acetate and concentrated. After ethyl ether was added to the residue, the solvent was distilled off to obtain the title compound (725 mg, yield: 71.7%) as a pale grayish solid. ? ti NMR (400 MHz, DMSO-d6) d ppm; 1.78 (2H, t, J = 5 Hz), 1. 85 (2H, t, J = 5 Hz), 2.05-2.21 (ÍH, m), 2.14 (3H, s), 3.48-3.62 (4H, m), 3.81 (2H, dd, J = 6, 12 Hz) , 4.05 (2H, dd, J = 4, 12 Hz), 4.15 (2H, d, J = 7 Hz), 4.71 (1H, d, J = 14 Hz), 4.80 (1H, d, J = 14 Hz) , 6.99 (1H, d, J = 6 Hz), 7.26-7.36 (2H, m), 7.58-7.72 (2H, br), 8.23 (1H, d, J = 6 Hz). (lOf) Sodium salt of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 92 To a solution of ethanol (15 ml) of 2- (((3-methyl-4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH -benzimidazole (708 mg, 1.55 mmole) obtained in step (10e), an IN of aqueous sodium hydroxide solution (1.54 ml, 1.55 mmole according to the concentration was estimated as 1.004 M) was added at room temperature and the mixture was concentrated. The residue was subjected to azeotropic distillation with ethanol twice. After the residue was suspended with diethyl ether, treated ultrasonically, and allowed to stand, the supernatant liquid was removed. This washing procedure was repeated twice more. The residue was dried under reduced pressure to obtain the title compound (635 mg, yield: 85.4%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.79 (2H, t, J = 5 Hz), 1.85 (2H, t, J = 5 Hz), 2.10-2.23 (HH, m), 2.19 (3H, s), 3.50-3.62 (4H, m), 3.78 -3.87 (2H, m), 4.05 (2H, dd, J = 4, 12 Hz), 4.14 (2H, d, J = 7 Hz), 4.40 (1H, d, J = 13 Hz), 4.78 (1H, d, J = 13 Hz), 6.82-6.90 (2H, m), 6.96 (1H, d, J = 6 Hz), 7.42-7.48 (2H, m), 8.29 (1H, d, J = 6 Hz). EXAMPLE 11 Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1 H -benzimidazole Formula 93 (lia) (2,2-dimethyl-l, 3-dioxan-5-yl) methanol Formula 94 A mixture of 2- (hydroxymethyl) -1,3-propandiol (4.09) g, 38.5 mmol), acetone (130 mL, 1768 mmol) and 70% perchloric acid (1.37 g, 9.55 mmol) was stirred at room temperature for 21 hours. After adjusting the pH of the reaction mixture with concentrated ammonia to 9, the reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (silica gel: 100 g, eluting solvent: heptane, heptane / ethyl acetate = 1/3) to obtain the title compound (4.83 g, yield: 85.8%) as a colorless oil. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.29 (3H, s), 1. 30 (3H, s), 1.64-1.74 (HH, m), 3.35-3.41 (2H, m), 3.61 (2H, dd, J = 7, 12 Hz), 3.82 (2H, dd, J = 4, 12 Hz), 4.54 (1H, t, J = 5 Hz). (llb) 2, 3, 5-trimethylpyridine-oxide Formula 95 To a dichloromethane (dehydrated) solution (150 ml) of 2, 3, 5-collidine (11.0 g, 90.8 mmol), 3-chloroperbenzoic acid (24.8 g, 93.4 mmol, according to the content was estimated as 65%) was added to 1 ° C in a nitrogen atmosphere. The mixture was stirred while the temperature was gradually raised to room temperature for 13.5 hours. After the reaction mixture was concentrated, the residue was purified by column chromatography on silica gel (NH silica gel: 200 g, eluting solvent: heptane / ethyl acetate = 50/50, ethyl acetate, ethyl acetate / methanol = 20 / L) to obtain a crude product of the title compound as a pale yellow solid. After the crude product was diluted with ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution, the mixture was concentrated. The residue was purified by column chromatography on silica gel (NH silica gel: 300 g, eluting solvent: heptane, heptane / ethyl acetate = 50/50, ethyl acetate, ethyl acetate / methanol = 20 / l) to get the title compound (11.0 g, yield: 88.3%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 2.15 (3H, s), 2.23 (3H, s), 2.27 (3H, s), 6.97 (1H, s), 7.99 (1H, s). (11c) 2, 3, 5-trimethyl-4-nitropyridine-oxide Formula 96 The 2,3,5-trimethylpyridine-oxide (11.0 g, 80.2 mmol) obtained in step (llb) was mixed with sulfuric acid (34.1 g, 348 mmol). Then acid was added Filling citric acid (5.50 ml, 133 mmol) by dripping to this mixture at room temperature, the mixture was stirred at 80 ° C for 9 hours. The reaction mixture was cooled to room temperature and then emptied on ice. The aqueous solution obtained was extracted with chloroform three times. The organic layers were combined and dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (13.6 g, yield: 93.1%) as a yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 2.16 (3H, s), 2. 20 (3H, s), 2.36 (3H, s), 8.35 (1H, s). (lid) 4-chloro-2, 3, 5-trimethylpyridinel-oxide Formula 97 The 2,3,5-trimethyl-4-nitropyridine oxide (13.4 g, 73.6 mmol) obtained in step (11c) was added to acetyl chloride (80 ml, 1.125 mmol) at -30 ° C under an atmosphere of nitrogen. The mixture was stirred at -30 ° C at room temperature for 4 hours and 20 minutes. After the reaction mixture was concentrated, the residue was subjected to column chromatography on silica gel (NH silica gel: 300 g, solvent elution: heptane, heptane / ethyl acetate = 50/50, ethyl acetate, ethyl acetate / methanol = 10 / l) to obtain fractions containing a pure product of the title compound and to obtain fractions containing a crude product of the title compound. Fractions containing a crude product of the title compound were concentrated. The residue was suspended in ethyl acetate and the resulting precipitate was collected by filtration, washed with ethyl acetate and diethyl ether to obtain the title compound (Lot A, 1.58 g) as a white solid. The filtrate was concentrated. The residue was dissolved in chloroform and washed with a saturated aqueous solution of sodium hydrogen carbonate., dried over anhydrous sodium sulfate, filtered and concentrated. The residue was suspended in diethyl ether. The resulting precipitate was collected by filtration, washed with diethyl ether to obtain the title compound (Lot B, 2.69 g) as a pale brown solid. Fractions containing a pure product of the title compound were concentrated. The residue was dissolved in chloroform, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (Lot C, 6.56 g) as a white solid. pale. The yield of the title compounds obtained 3 lots was 85.7% in total. Lot A: XH NMR (400 MHz, DMS0-d6) d PPM; 2.24 (3H, s), 2.35 (3H, s), 2.39 (3H, s), 8.25 (1H, s). Lot B: XH NMR (400 MHz, DMSO-d6) d PPM; 2.24 (3H, s), 2.35 (3H, s), 2.39 (3H, s), 8.25 (1H, s). Lot C: 1 H NMR (400 MHz, DMSO-de) d PPM; 2.24 (3H, s), 2.35 (3H, s), 2.39 (3H, s), 8.25 (1H, s). (lie) 4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -2,3,5-trimethylpyridine-oxide Formula 98 To a solution of dimethylsulfoxide (50 ml) of (2,2-dimethyl-1,3-dioxan-5-yl) methanol (4.78 g, 32.7 mmol) obtained in step (IIa), hydride was added at room temperature. sodium, in oil (1.26 g, 31.5 mmol according to the content was estimated as 60%). The mixture was stirred at room temperature for 15 minutes in a nitrogen atmosphere. To the mixture, 4-chloro-2,3,5-trimethylpyridine-oxide (Lot C, 4.50 g, 26.2 mmol) obtained in step (lid) was added and the mixture was stirred at 60 ° C for 8 hours and 10 minutes. After cooling to room temperature, the reaction mixture was concentrated. The residue is purified by silica gel column chromatography (NH silica gel: 300 g, eluting solvent: heptane, heptane / ethyl acetate = l / l, 1/3, ethyl acetate, ethyl acetate / methanol = 10 / L ) to obtain the title compound (5.06 g, yield: 68.6%) as a yellow oil. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.05-2.13 (lH, m), 2.14 (3H, s), 2.17 (3H, s), 2.31 (3H, s), 3.77-3.86 (4H, m), 4.01 (2H, dd, J = 4, 12 Hz), 8.07 (ÍH, s). (llf) (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methanol Formula 99 The 4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -2,3,5-trimethylpyridine-oxide (5.06 g, 18 mmol) obtained in step (lie) was mixed with acetic anhydride (50 ml, 529 mmol) and the mixture was stirred at 85 ° C for 1.5 hours. After cooling to room temperature, the reaction mixture was concentrated. Methanol (50 ml) and 5N of aqueous sodium hydroxide solution (50 ml, 250 mmol) were added to the residue and the mixture was stirred at room temperature for 30 minutes. The The reaction mixture was concentrated and the residue was partitioned between water and ethyl acetate. The organic layer was washed with IN Na of aqueous sodium hydroxide solution twice and dried over anhydrous magnesium sulfate, filtered and concentrated to obtain the title compound (3.02 g, yield: 59.6%) as an oil. Brown color. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.37 (3H, s), 2.05-2.16 (lH, m), 2.20 (6H, s), 3.82 (2H, dd, J = 6, 12 Hz), 3.86 (2H, d, J = 8 Hz), 4.02 (2H, dd, J = 4, 12 Hz), 4.5K2H, d, J = 6 Hz), 4.98 (1H, t, J = 6 Hz), 8.16 (1H, s). (llg) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 100 To a solution of tetrahydrofuran (15 ml) of (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methanol (504 mg, 1.79 g. mmoles) obtained in step (llf) and triethylamine (500 [mu] l, 3.58 mmol), methanesulfonyl chloride (208 [mu] l, 2.69 mmol) was added by dripping from 1 ° C to 3 ° C for 15 minutes in a nitrogen atmosphere. The reaction mixture was stirred for 1 hour and 25 minutes in the same terms. Then 2-mercaptobenzimidazole (271 mg, 1.8 mmol) was added, the mixture was stirred at room temperature for 64 hours and 20 minutes. The reaction mixture was separated between ethyl acetate and a saturated aqueous solution of sodium acid carbonate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (silica gel: 30 g, eluting solvent: heptane / ethyl acetate = 42/58, 22/78, ethyl acetate) to obtain the title compound (442 mg , yield: 59.7%) as a colorless foam. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.05-2.16 (lH, m), 2.20 (3H, s), 2.28 (3H, s), 3.81 (2H, dd, J = 6, 12 Hz) , 3.87 (2H, d, J = 7 Hz), 4.02 (2H, dd, J = 4, 12 Hz), 4.69 (2H, s), 7.09-7.16 (2H, m), 7.41-7.50 (2H, m ), 8.18Í1H, s). (Xñ NMR) 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 101 To a solution of toluene (20 ml) -methanol (2 ml) of 2- (((4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -lH-benzimidazole (424 mg, 1.03 mmoles) obtained in step (llg), to toluene (1 ml) -methanol (1 ml) was added a solution of 3-chloroperbenzoic acid (246 mg, 0.927 mmoles according to the content was estimated as 65%) by drip -65 ° C for 5 minutes in a nitrogen atmosphere. The mixture was stirred for 45 minutes under the same conditions. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (silica gel NH: 20 g, eluting solvent: dichloromethane, dichloromethane / methanol = 10 / l). The fractions containing the title compound were collected with ethyl acetate and concentrated. To the residue, diethyl ether was added. The resulting precipitate was collected by filtration and washed with diethyl ether to obtain the title compound (274 mg, yield: 61.9%) as a white solid. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.32 (3H, s), 1.36 (3H, s), 2.02-2.13 (lH, m), 2.16 (3H, s), 2.20 (3H, s), 3.74-3.84 (4H, m), 4.00 (2H, dd, J = 4, 12 Hz), 4.70 (1H, d, J = 14 Hz), 4.79 (1H, d, J = 14 Hz), 7.26-7.33 (2H, m), 7.60-7.70 (2H, m ), 8.18 (ÍH, s). (lli) Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) - IH-benzimidazole Formula 102 To a solution of ethanol (10 ml) of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethyl-2-yl) methyl) sulfinyl) -lH-benzimidazole (274 mg, 0.638 mmol) obtained in step (11 H NMR), IN was added aqueous sodium hydroxide solution (635 [mu] l, 0.638 mmol as the concentration was estimated as 1,004 M) at room temperature and the mixture was concentrated. The residue was subjected to azeotropic distillation with ethanol twice. After the residue was suspended in diethyl ether, the mixture was treated ultrasonically and concentrated to obtain the title compound (260 mg, yield: 90.3%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.03-2.14 (HH, m), 2.20 (3H, s), 2.21 (3H, s), 3.76-3.87 (4H, m), 4.00 (2H, dd, J = 4, 11 Hz), 4.39 (1H, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.81-6.91 (2H, m), 7.40-7.48 (2H, m ), 8.23 (1H, s).

EXAMPLE 12 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 103 (12a) 4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -2,3-dimethylpyridinone-oxide Formula 104 To a solution of dimethyl sulfoxide (30 ml) of (2,2-dimethyl-1,3-dioxan-5-yl) methanol (3.27 g, 22.4 mmol) separately obtained in the same manner as in step (lia) in Example 11, sodium hydride was added, in oil (837 mg, 20.9 mmol according to the content was estimated as 60%) at room temperature. The mixture was stirred at room temperature for 15 minutes in a nitrogen atmosphere. To the mixture, 4-chloro-2,3-dimethylpyridine-oxide (3.03 g, 19. 2 mmol), and the mixture was stirred at 60 ° C for 3 hours and 20 minutes. After cooling to room temperature, the reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (NH silica gel: 250 g, eluting solvent: ethyl acetate, ethyl acetate / methanol = 10/1) to obtain the title compound (3.84 g, yield: 74.8%) as a pale brown solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.31 (3H, s), 1.35 (3H, s), 2.00-2.12 (lH, m), 2.12 (3H, s), 2.33 (3H, s), 3.74 (2H, dd, J = 6, 12 Hz) , 3.97 (2H, dd, J = 4, 12 Hz), 4.08 (2H, d, J = 7 Hz), 6.94 (1H, d, J = 7 Hz), 8.05 (1H, d, J = 7 Hz) . (12b) (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol Formula 105 The 4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -2,3-dimethylpyridine oxide (3.84 g, 14.4 mmol) obtained in step (12a) was mixed with acetic anhydride (50 ml, 530 mmol). The mixture was stirred at 85 ° C for 1.5 hours. After cooling to room temperature, the reaction mixture was concentrated. To the residue, methanol (50 ml) and 5N of aqueous sodium hydroxide solution (20 ml, 100 mmol) were added and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was concentrated and the residue was partitioned between water and ethyl acetate. The organic layer was washed with 2N aq of aqueous sodium hydroxide solution, dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (2.97 g, yield: 77.2%) as a white solid. Brown color. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.31 (3H, s), 1. 34 (3H, s), 2.03-2.14 (ÍH, m), 2.10 (3H, s), 3.76 (2H, dd, J = 6, 12 Hz), 3.98 (2H, dd, J = 4, 12 Hz) , 4.10 (2H, d, J = 7 Hz), 4.5K2H, d, J = 5 Hz), 4.97 (1H, t, J = 5 Hz), 6.95 (1H, d, J = 6 Hz), 8.22 ( ÍH, d, J = 6 Hz). (12c) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole Formula 106 To a solution of dichloromethane (dehydrated) (20 ml) of (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol (1.03 g, 3.85 mmoles) obtained in Step (12b) and triethylamine (1.07 ml, 7.7 mmol), methanesulfonyl chloride (447 μl, 5.78 mmol) was added dropwise at a temperature of 1 ° C to 4 ° C for 10 minutes under nitrogen atmosphere. The mixture was stirred for one hour and 25 minutes under the same conditions. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was mixed with 2-mercaptobenzimidazole (586 mg, 3.9 mmol) and the mixture was stirred in methanol (20 ml) at room temperature for 2 hours and 40 minutes. NH silica gel (15 g) was added to the reaction mixture, which was then concentrated. The residue was subjected to silica gel column chromatography (NH silica gel: 20 g, eluting solvent: heptane / ethyl acetate = 1 / l, 1/3, ethyl acetate) to obtain a mixture of the title compound and 2-mercaptobenzimidazole. The mixture was further purified by column chromatography on silica gel (silica gel: 30 g, eluting solvent: heptane / ethyl acetate = 50/50, 25/75, ethyl acetate) to obtain the title compound (771 mg, yield: 50.1%) as a colorless foam. H NMR (400 MHz, DMSO-d6) d PPM; 1.31 (3H, s), 1.34 (3H, s), 2.03-2.15 (lH, m), 2.20 (3H, s), 3.76 (2H, dd, J = 6, 12 Hz), 3.98 (2H, dd, J = 4, 12 Hz), 4.11 (2H, d, J = 7 Hz), 4. 68 (2H, s), 6.97 (1H, d, J = 6 Hz), 7.06-7.14 (2H, m), 7.35-7.5K2H, br), 8.23 (1H, d, J = 6 Hz), 12.60 ( ÍH, br s). (12d) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 107 To a solution of toluene (45 ml) -methanol (5 ml) of 2- (((4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole (766 mg, 1.92 mmol ) obtained in step (12c), a solution of toluene (0.5 ml) -methanol (0.5 ml) of 3-chloroperbenzoic acid (459 mg, 1.73 mmol according to the content was estimated as 65%) at -65 ° was added dropwise. C for 5 minutes in a nitrogen atmosphere. The mixture was stirred under the same conditions for one hour and 20 minutes. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate was added. The aqueous layer was extracted with ethyl acetate and chloroform (three times).

The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (NH silica gel: 30 g, solvent elution: dichloromethane, dichloromethane / methanol = 20 / l). The fractions containing the The title compound was collected, concentrated to obtain the title compound (688 mg, yield: 86.2%) as a light brown foam XH NMR (400 MHz, DMSO-d6) d PPM; 1.31 (3H, s), 1.34 (3H, s), 2.03-2.12 (lH, m), 2.12 (3H, s), 3.75 (2H, dd, J = 6, 12 Hz), 3.98 (2H, dd, J = 4, 12 Hz), 4.11 (2H, d, J = 7 Hz), 4. 69 (1H, d, J = 14 Hz), 4.78 (1H, d, J = 14 Hz), 6.97 (1H, d, J = 6 Hz), 7.24-7.34 (2H, m), 7.57-7.70 (2H, m), 8.20 (1H, d, J = 6 Hz). (12e) Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H- Benzimidazole Formula 108 To a solution of ethanol (10 ml) of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (688 mg, 1.66 mmol) obtained in step (12d), IN was added aqueous sodium hydroxide solution (1.65 ml, 1.66 mmole according to the concentration was estimated as 1.004 M) at room temperature and the mixture He concentrated. The residue was subjected to azeotropic distillation with ethanol twice. After the The residue was suspended in diethyl ether, the mixture was treated ultrasonically and allowed to stand. Next, the supernatant fluid was removed. This washing procedure was repeated two more times and the residue was dried under reduced pressure to obtain the title compound (701 mg, yield: 96.5%) as a white solid. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.32 (3H, s), 1. 34 (3H, s), 2.04-2.13 (lH, m), 2.17 (3H, s), 3.72-3.81 (2H, m), 3. 98 (2H, dd, J = 4, 12 Hz), 4.10 (2H, d, J = 7 Hz), 4.38 (1H, d, J = 13 Hz), 4.76 (1H, d, J = 13 Hz), 6.80-6.89 (2H, m), 6.94 (1H, d, J = 5 Hz), 7.39-7.47 (2H, m), 8.28 (1H, d, J = 5 Hz). EXAMPLE 13 Sodium salt of 2- (((4- (5,9-dioxaspiro [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 109 13a) 5, 9-dioxasprio [3.5] non-7-ylmethanol Formula 110 A mixture of 2- (hydroxymethyl) -1,3-propanediol (5.58 g, 52.6 mmol), cyclobutanone (3.69 g, 52.6 mmol), p-toluenesulfonic acid monohydrate (550 mg, 2.89 mmol) and benzene (92.9 ml) were added. refluxed in a round bottom flask equipped with a cooling tube and Dean-Stark for 8 hours and 35 minutes. After the reaction mixture was cooled to room temperature, triethylamine (1 ml) was added to the reaction mixture and the mixture was concentrated. The residue was purified by column chromatography on silica gel (silica gel: 300 g, eluting solvent: heptane, heptane / ethyl acetate = 1/1). The fractions containing the title compound were collected with ethyl acetate and concentrated. The residue was dissolved in diethyl ether and the mixture was concentrated to obtain the title compound (6.08 g, yield: 73.1%) as a pale yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.58-1.68 (2H, m), 1.68-1.77 (ÍH, m), 2.07-2.16 (4H, m), 3.32-3.39 (2H, m), 3.52 (2H, dd, J = 7, 12 Hz), 3.78 (2H, dd, J = 4, 12 Hz), 4.56 (1H, t, J = 5 Hz). (13b) 4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -2,3,5-trimethylpyridine-oxide Formula 111 To a solution of dimethisulfoxide (20 ml) of 5,9-dioxasprio [3.5] non-7-ylmethanol (2.20 g, 13.9 mmol) obtained in step (13a), sodium hydride was added in oil (524 mg, 13.1 mmoles according to the content was estimated as 60%) at room temperature. The mixture was stirred at room temperature for 45 minutes in a nitrogen atmosphere. To the mixture, 4-chloro-2,3,5-trimethylpyridine-oxide (Lot C, 1.94 g, 11.3 mmol) obtained in step (lid) in Example 11 was added, the mixture was stirred at 60 ° C for 2 hours. hours and 50 minutes. After cooling to room temperature, the reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (NH silica gel: 100 g, eluting solvent: heptane, heptane / ethyl acetate = 1 μl, ethyl acetate, ethyl acetate / methanol = 20 μl) to obtain the title compound (1.97 g, yield: 59.4%) as a brown oil. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.60-1.71 (2H, m), 2.07-2.22 (5H, m), 2.12 (3H, s), 2.16 (3H, s), 2.30 (3H, s), 3. 74 (2H, dd, J = 7, 12 Hz), 3.78 (2H, d, J = 7 Hz), 3.94 (2H, dd, J = 4, 12 Hz), 8.05 (ÍH, s). (13c) (4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methanol Formula 112 The 4- (5, 9-dioxasprio [3.5] non-7-ylmethoxy) -2,3,5-trimethylpyridine-oxide (1.97 g, 6.72 mmol) obtained in step (13b) was mixed with acetic anhydride (20 ml, 212 mmol). The mixture was stirred at 85 ° C for 1.5 hours. After cooling to room temperature, the reaction mixture was concentrated. To the residue, methanol (20 ml) and 5N aqueous sodium hydroxide solution (20 ml, 100 mmol) were added and the mixture was stirred at room temperature for 45 minutes. The reaction mixture was concentrated and the residue was partitioned between water and ethyl acetate. The organic layer was washed with 2N aqueous sodium hydroxide solution, dried over anhydrous magnesium sulfate, filtered and concentrated to obtain the title compound (1.69 g, yield: 85.7%) as a brown oil. H NMR (400 MHz, DMSO-d6) d PPM; 1.60-1.70 (2H, m), 2. 08-2.25 (5H, m), 2.18 (6H, s), 3.75 (2H, dd, J = 6, 12 Hz), 3.83 (2H, d, J = 7 Hz), 3.95 (2H, dd, J = 4, 12 Hz), 4.50 (2H, d, J = 5 Hz), 4.97 (1H, t, J = 5 Hz), 8.14 (1H, s). (13d) 2- (((4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethyl-ilpyridin-2-yl) methyl) thio) -IH-benzimidazole Formula 113 To a solution of dichloromethane (dehydrated) (15 ml) and tetrahydrofuran (5 ml) of (4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methanol ( 450 mg, 1.53 mmol) obtained in step (13c) and triethylamine (427 μl, 3.06 mmol), methanesulfonyl chloride (178 μl, 2.3 mmol) of 1 ° C was added dropwise. at 4 ° C for 10 minutes in a nitrogen atmosphere. The mixture was stirred for 50 minutes under the same conditions. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was mixed with 2-mercaptobenzimidazole (235 mg, 1.56 mmol) and the mixture was stirred in methanol (20 ml) at room temperature for 2 hours and 30 minutes. NH silica gel (15 g) was added to the mixture of reaction, which was then concentrated. The residue was subjected to silica gel column chromatography (silica gel: 30 g, eluting solvent: heptane / ethyl acetate = 42/58, 22/78, ethyl acetate) for the title compound (507 mg, yield: 77.9%) as a colorless foam. ? NMR (400 MHz, DMSO-d6) d PPM; 1.60-1.71 (2H, m), 2. 08-2.22 (5H, m), 2.19 (3H, s), 2.28 (3H, s), 3.76 (2H, dd, J = 6, 12 Hz), 3.84 (2H, d, J = 7 Hz), 3.95 (2H, dd, J = 4, 12 Hz), 4. 69 (2H, s), 7.06-7.19 (2H, m), 7.37-7.56 (2H, br), 8.18 (1H, s), 12.60 (1H, br s). (13e) 2- (((4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 114 To a solution of toluene (20 ml) -methanol (2 ml) of 2- (((4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methyl ) thio) -lH-benzimidazole (499 mg, 1.17 mmol) obtained in step (13d), a solution of toluene (1 ml) -methanol (1 ml) of 3-chloroperbenzoic acid (280 mg, 1.05 g) was added dropwise. mmoles according to the content was estimated as 65%) at -65 ° C for 5 minutes in an atmosphere of nitrogen. The mixture was stirred under the same conditions for 55 minutes. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate was added. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (NH silica gel: 20 g, eluting solvent: dichloromethane, dichloromethane / methanol = 20 / l). The fractions containing the title compound were collected with ethyl acetate, and concentrated. To the residue, diethyl ether was added and then the mixture was concentrated to obtain the title compound (445 mg, yield: 86.1%) as a colorless foam. * H NMR (400 MHz, DMSO-d6) d PPM; 1.60-1.70 (2H, m), 2.06-2.23 (5H, m), 2.14 (3H, s), 2.18 (3H, s), 3.67-3.82 (4H, m), 3.93 (2H, dd, J = 4 , 12 Hz), 4.70 (1H, d, J = 14 Hz), 4.78 (1H, d, J = 14 Hz), 7.25-7.34 (2H, m), 7.58-7.70 (2H, m), 8.18 (H) , s). (13f) Sodium salt of 2 - (((4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 115 To a solution of ethanol (10 ml) of 2- (((4- (5,9-dioxasprio [3.5] non-7-ylmethoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -lH- Benzimidazole (445 mg, 1.01 mmol) obtained in step (13e), was added at room temperature ÍN of aqueous sodium hydroxide solution (1.01 ml, 1.01 mmol according to the concentration was estimated as 1.004M) and the mixture was concentrated. The residue was subjected to azeotropic distillation with ethanol twice. After the residue was suspended with diethyl ether, the mixture was treated ultrasonically and concentrated to obtain the title compound (420 mg, yield: 89.7%) as a white solid. H NMR (400 MHz, DMSO-d6) d PPM; 1.58-1.70 (2H, m), 2.07-2.25 (5H, m), 2.19 (6H, s), 3.68-3.82 (4H, m), 3.94 (2H, dd, J = 4, 12 Hz), 4.34- 4.41 (HH, m), 4.70-4.77 (HH, m), 6.82-6.89 (2H, m), 7.41-7.47 (2H, m), 8.22 (1H, s). EXAMPLE 14 Sodium salt of 2- (((4- (((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -ÍH- Benzimidazole Formula 116 (14a) 4- (((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -2, 3-dimethylpyridine-oxide Formula 117 To a solution of dimethylsulfoxide (48 ml) of ((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) methanol (4.87 g, 39.7 mmol), sodium hydride was added in oil (1.73 g, 39.6 mmol, according to the content was estimated as 55%) at room temperature. To the mixture, 4-chloro-2,3-dimethylpyridine oxide (4.8 g, 30.5 mmol) was added, the mixture was stirred at 60 ° C for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / methanol) to obtain the title compound (10.5 g, yield: 136%) as a yellow oil. 1 H NMR (400 MHz, CDC13) d PPM; 1.40 (3H, s), 1.45 (3H, s), 2.21 (3H, s), 2.54 (3H, s), 3.93 (1H, dd, J = 6, 8 Hz), 4.01 (1H, dd, J = 5, 10 Hz), 4.07 (1 H, dd, J = 5, 10 Hz), 4.17 (1 H, dd, J = 6, 8 Hz), 4.48 (H, quint, J = 6 Hz), 6.65 (1 H, d, J = 8 Hz), 8. 15 (ÍH, d, J = 8 Hz). (14b) (4- (((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methanol Formula 118 The 4- (((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -2,3-dimethylpyridine-oxide (10.5 g, 41.5 mmol) obtained in step (14a) is mixed with acetic anhydride (20 ml). The mixture was stirred at 80 ° C for one hour. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. To the residue, methanol (40 ml) and 5N aqueous sodium hydroxide solution (20 ml) were added and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated and the residue was partitioned between saturated saline and ethyl acetate. The organic layer dried over anhydrous magnesium sulfate, filtered and concentrated and the residue was purified by column chromatography on silica gel (elution solvent: ethyl acetate / methanol) to obtain the title compound (3.77 g, yield: 41.9% ) as a yellow oil. XH NMR (400 MHz, CDC13) d PPM; 1.41 (3H, s), 1.46 (3H, s), 2.5 (3H, s), 3.95 (1H, dd, J = 6, 8 Hz), 4.03 (1H, dd, J = 5, 10 Hz), 4.11 (1H, dd, J = 5, 10 Hz), 4.18 (1H, dd, J = 6, 8 Hz), 4. 49 (1H, quint, J = 6 Hz), 4.65 (2H, s), 4.84 (1H, br s), 6.71 (1H, d, J = 8 Hz), 8.29 (1H, d, J = 8 Hz) . (14c) 2 - (((4 - (((4R) -2, 2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH- Benzimidazole Formula 119 To a solution of tetrahydrofuran (dehydrated), (50 mL) of (4- (((4R) -2, 2-dimethyl-1,3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methanol (3.77 g, 14.9 mmol) obtained in step (14b) and triethylamine (4.15 ml, 29.8 mmol), methanesulfonyl chloride (1.73 ml, 22.4 mmol) was added dropwise under cooling with ice under a nitrogen atmosphere, and the mixture was stirred for 1.5 hours under the same conditions. The reaction mixture was emptied in a solution aqueous saturated sodium carbonate acid and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and solvent was distilled. From the obtained residue (3.8 g, yield of a crude product: 77%), a portion of 1.2 g (3.62 mmol) was taken and dissolved in ethanol (20 ml), and 2-mercaptobenzimidazole (598 mg, 3.98 g) was added. mmoles) thereto and the mixture was stirred at room temperature for 14 hours. The reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: heptane / ethyl acetate) to obtain the title compound (580 mg, yield: 41.6%) as a light yellow foam. 1 H NMR (400 MHz, CD30D) d ppm; 1.37 (3H, s), 1.39 (3H, s), 2.33 (3H, s), 3.94 (1H, dd, J = 6, 8 Hz), 4.19 (1H, dd, J = 6, 8 Hz), 4.32 (1H, dd, J = 5, 1Hz), 4.40 (1H, dd, J = 4, 1Hz), 4.52-4.60 (1H, m), 4.75 (2H, s), 7.25 (2H, dd, J = 3 , 6 Hz), 7.39 (1H, d, J = 8 Hz), 7.53 (2H, dd, J = 3, 6 Hz), 8.47 (1H, d, J = 8 Hz). (14d) 2- (((4- (((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H- benzimidazole Formula 120 To a solution of toluene-methanol (10: 1) (22 ml) of 2 - (((4 - (((4R) -2,2-dimethyl-1,3-dioxolan-4-yl) methoxy) -3 methyl-pyridin-2-yl) methyl) thio) -lH-benzimidazole (580 mg, 1.5 mmol) obtained in step (14c), a solution of toluene-methanol (10: 1) (11 ml) was added dropwise. 3-chloroperbenzoic acid (353 mg, 1.33 mmol depending on the content was estimated as 65%) from -50 ° C to -60 ° C for 5 minutes in a nitrogen atmosphere. The mixture was stirred under the same conditions for 3 hours. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution was added and extracted with ethyl acetate. The organic layer was concentrated and the residue was purified by column chromatography on silica gel (NH silica gel, elution solvent: ethyl acetate / methanol) to obtain the title compound (330 mg, yield: 54.8%) as a clear yellow foam. This compound was converted to the sodium salt according to the following operation and confirmed for the structure thereof. (14e) Sodium salt of 2- (((4- (((4R) -2,2-dimethyl-1,3-dioxolan-4-yl) methoxy) -3-methylpyridin-2- il) methyl) sulfinyl) -lH-benzimidazole Formula 121 To an ethanol solution of (6 ml) of 2- (((4- (((4R) -2, 2-dimethyl-l, 3-dioxolan-4-i1) methoxy) -3-methylpyridin-2-ylmethyl) sulfinyl) -lH-benzimidazole (330 mg, 822 μmol) obtained in step (14d), IN was added aqueous sodium hydroxide solution (822 μl, 822 μmol) at room temperature and the mixture was stirred for 30 minutes. After the mixture was concentrated and ethyl ether was added to the residue, the mixture was treated ultrasonically The solid generated was collected by filtration under a nitrogen atmosphere The solid was dried under reduced pressure to obtain the title compound (314 mg, yield : 90.2%) as a light yellow solid. Ñ NMR (400 MHz, DMSO-d6) d PPM, 1.30 (3H, s), 1. 36 (3H, s), 2.19 (3H, s), 3.80 (1H, dd, J = 6, 8 Hz), 4.02-4.14 (3H, m), 4.37 (1H, d, J = 14 Hz), 4.43 (1H, quint, J = 6 Hz), 4.79 (1H, d, J = 14 Hz), 6.83 (2H, dd, J = 3, 6 Hz), 6.93 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.36 (1H, d, J = 6 Hz). (14f) Optical isomer (short in retention time) of 2- (((4- (((4R) -2, 2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 122 To a mixed solution of toluene (dehydrated) (0.5 ml) and water (1.73 μl, 95.9 μmol) of 2- (((4- (((4R) -2,2-dimethyl-1,3-dioxolan-4-) il) methoxy) -3-methylpyridin-2-yl) methyl) thio) -lH-benzimidazole (84 mg, 218 μmol) obtained in step (14c), L (+) - diethyl tartrate (32.9 μl, 192 μmol) and stirred at 50 ° C for 15 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (28.3 μL, 95.9 μmol) was added to the reaction mixture and stirred for a further 1 hour. After the reaction mixture was cooled on ice, N, N-diisopropylethylamine (33.4 μl, 192 μmol) was added and eumeno hydroperoxide (121 μl, 654 μmol according to the content was estimated as 80%) was added by dripping in an atmosphere of nitrogen and stirred at 0 ° C at room temperature for 17 hours. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and solvent was distilled under reduced pressure.

The residue was purified by column chromatography on silica gel (NH silica gel, elution solvent: ethyl acetate / methanol) to obtain the title compound (45 mg, yield: 51.4%) as a light yellow foam. This compound was converted into a sodium salt according to the following operation and was confirmed for the structure. (14g) Sodium salt of an optical isomer (short in retention time) of 2- (((4- (((4R) -2, 2-dimethyl-l, 3-dioxolan-4-yl) methoxy) - 3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 123 To a solution of ethanol (3 ml) of an optical isomer (short in retention time) of 2- (((4- (((4R) -2, 2-dimethyl-1,3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -IH-benzimidazole (45 mg, 112 μmol) obtained in step (14f), added IN of aqueous sodium hydroxide solution (112 μL, 112 mmol) at room temperature and the mixture was stirred for 30 minutes. After the mixture was concentrated and ethyl ether was added to the residue, the mixture was treated ultrasonically. The generated solid was collected by filtration in a nitrogen atmosphere.

The solid was dried under reduced pressure to obtain the title compound (22 mg, yield: 46.4%) as a light yellow solid. X H NMR (400 MHz, DMS0-d 6) d PPM; 1.30 (3H, s), 1.35 (3H, s), 2.19 (3H, s), 3.80 (1H, dd, J = 6, 8 Hz), 4.02-4.14 (3H, m), 4.37 (1H, d, J = 13 Hz), 4.42 (1H, quint, J = 5 Hz), 4.79 (1H, d, J = 13 Hz), 6.83 (2H, dd, J = 3, 6 Hz), 6.93 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cmfx25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.3 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 31.6 minutes, diastereomeric excess: 92% (14h) Optical Isomer (Length in Retention Time) of 2- (((4- (((4R) ) -2, 2-dimethyl-1,3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 124 To a solution of toluene (dehydrated) (1.0 ml) and water (3.5 μl, 194 μmol) of 2- (((4- (((4R) -2, 2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl ) thio) -1H-benzimidazole (170 mg, 441 μmol) obtained in step (14c), D- (-) -diethyl tartrate (66.6 μl, 389 μmol) was added and stirred at 50 ° C for 15 minutes in a nitrogen atmosphere. To the reaction mixture, titanium (IV) isopropoxide (57.3 μl, 194 μmol) was added and stirred for an additional hour. After the reaction mixture was cooled on ice, N, N-diisopropylethylamine (67.6 μl, 389 μmol) was added to the reaction mixture and eumeno hydroperoxide (245 μl, 1.32 mmol according to the content was estimated as 80%) was added. drip thereto in a nitrogen atmosphere and the mixture was stirred at 0 ° C at room temperature for 17 hours. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture and extracted with ethyl acetate. After the organic layer was dried over sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (NH silica gel, eluting solvent: ethyl acetate / methanol) to obtain the title compound (104 mg, yield: 58.7%) as a light yellow foam. This compound was converted into a sodium salt according to the following operations and was confirmed for the structure. (14i) Sodium salt of Optical Isomer (Length in Retention Time) of 2- (((4- (((4R) -2, 2-dimethyl-l, 3- dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 125 To a solution of ethanol (3 ml) of the optical isomer (long in retention time) of 2- (((4- (((4R) -2, 2-dimethyl-1,3-dioxolan-4-yl) methoxy ) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (104 mg, 259 μmol) obtained in step (14h), IN was added aqueous sodium hydroxide solution (259 μl, 259 μmol) at room temperature and the mixture was stirred for 30 minutes. After the mixture was concentrated and ethyl ether was added to the residue, the mixture was treated ultrasonically. The generated solid was collected by filtration in a nitrogen atmosphere. The solid was dried under reduced pressure to obtain the title compound (99 mg, yield: 90%) as a light yellow solid. H NMR (400 MHz, DMSO-d6) d PPM; 1.30 (3H, s), 1.35 (3H, s), 2.19 (3H, s), 3.80 (1H, dd, J = 6, 8 Hz), 4.02-4.14 (3H, m), 4.37 (1H, d, J = 13 Hz), 4.42 (1H, quint, J = 5 Hz), 4.79 (1H, d, J = 13 Hz), 6.82-6.88 (2H, m), 6.93 (1H, d, J = 6 Hz) , 7. 38-7.46 (2H, m), 8.26 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.3 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 35.9 minutes, diastereomeric excess: 89% of Example 15 Sodium salt of an optical isomer (Length in Retention Time) of 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 126 Na (15a) Optical Isomer (Length in Retention Time) of 2- (((4- ((5, 5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 127 H A suspension of toluene (dehydrated) (2.8 ml) -water (1.4 μl, 0.0777 mmol) of 2- (((4- ((5, 5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3 -methylpyridin-2-yl) methyl) thio) -1H-benzimidazole (250 mg, 0.626 mmol) obtained in the same manner as in steps (la) to (le) of Example 1 and D - (-) - diethyl tartrate (47 μl, 0.275 mmole) was stirred at 50 ° C for 30 minutes in a nitrogen atmosphere. Toluene (dehydrated) (1.2 ml) was also added to the mixture, which was stirred for 30 minutes under the same conditions. Titanium (IV) isopropoxide (37 μL, 0.125 mmol) was added and the resulting mixture was stirred for one hour under the same conditions. After cooling to room temperature and N, N-diisopropylethylamine (35 μL, 0.201 mmol) was added to the mixture, the resulting mixture was stirred for 10 minutes under cooling with ice. Then eumeno hydroperoxide (360 μl, 1.95 mmoles according to the content was estimated as 80%) was added by dripping at an internal temperature of 0 ° C to 2 ° C, for 5 minutes, the mixture was stirred at an internal temperature of 0 ° C at 3 ° C for 4 hours. After finishing the reaction by a saturated aqueous solution of sodium hydrogen carbonate, ethyl acetate and water were added thereto. The separated aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, a saturated saline solution, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate / methanol gradient = 1 / 0-4 / 1). The desired fractions were concentrated to obtain the title compound (203 mg, content: 88.9%, yield: 69.4%) as a light brown foam XH NMR (400 MHz, DMSO-d6) d PPM; 0.69 (3H, s), 1. 1K3H, s), 2.13 (3H, s), 3.48 (2H, d, J = ll Hz), 3.58 (2H, d, J = ll Hz), 4.08 (2H, d, J = 4 Hz), 4.69 (1H, d, J = 14 Hz), 4.77 (1H, d, J = 14 Hz), 4.83 (1H, t, J = 4 Hz), 6.97 (1H, d, J = 6 Hz), 7.24-7.32 (2H, m), 7.58-7.67 (2H, m), 8.20 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cmfx25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 18.9 minutes, enantiomeric excess: 87% ee Optical Isomer sodium salt (Length in Retention Time) of 2- (((4- ((5 , 5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3- methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 128 Na To a solution of ethanol (3 ml) of an optical isomer (long in retention time) of 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) - 3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (200 mg, content: 88.9%, 0.428 mmol) obtained in step (15a), IN was added aqueous sodium hydroxide solution (428 μl, 0.428 mmoles) at room temperature and the mixture was stirred for 10 minutes under the same conditions. After the mixture was concentrated and ethanol was added to the residue, the mixture was subjected to azeotropic distillation and suspended with diethyl ether. The suspension was ultrasonically treated and allowed to stand. The supernatant liquid was removed and then the residue was dried to obtain the title compound (145 mg, 77.4% yield) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 0.68 (3H, s), 1.1K3H, s), 2.17 (3H, s), 3.48 (2H, d, J = ll Hz), 3.58 (2H, d, J = ll Hz), 4.06 (2H, d, J = 4 Hz), 4.37 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 4.83 (1H, t, J = 4 Hz), 6.81-6.88 (2H, m) 6.93 (1H, d, J = 6 Hz), 7.39-7.46 (2H, m), 8.25 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cmfx25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 18.4 minutes, enantiomeric excess: 87.4% ee specific rotation: aD25"5 = -123.83 (c = 0.5, EtOH) Example 16 Sodium salt of Optical Isomer (Short in retention time) of 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH -benzimidazole Formula (16a) Optical Isomer (Short in retention time) of 2- (((4- ((5, 5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl sulfinyl) -lH-benzimidazole Formula 130 H A suspension of toluene (dehydrated) (4.0 ml) -water (1.4 μl, 0.0777 mmol) of 2- (((4- ((5, 5-dimethyl-l, 3-dioxan-2-yl) methoxy) -3 -methylpyridin-2-yl) methyl) thio) -1H-benzimidazole (250 mg, 0.626 mmol) obtained in the same manner as in steps (la) to (le) of Example 1 and L - (+) diethyl tartrate (47 μl, 0.274 mmol) was stirred at 50 ° C for 10 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (37 μL, 0.125 mmol) was added to the resulting mixture and stirred for one hour under the same conditions. After cooling to room temperature, N, N-diisopropylethylamine (35 μL, 0.201 mmol) was added to the mixture, and the resulting mixture was stirred for 15 minutes under ice-cooling. Then eumeno hydroperoxide (360 μl, 1.95 mmoles according to the content was estimated as 80%) was added by dripping at an internal temperature of 0 ° C to 2 ° C, for 5 minutes, the mixture was stirred at an internal temperature of 0 ° C at 3 ° C for 4 hours. After the reaction was terminated by a saturated aqueous sodium hydrogen carbonate solution, ethyl acetate and water were added thereto. The aqueous layer separated was extracted with ethyl acetate. The organic layers were combined, washed with water and a saturated saline solution, dried over anhydrous sodium sulfate and concentrated. The residue obtained was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate / methanol = l / 0-4 / l gradient). The desired fractions were concentrated to obtain the title compound (208 mg, content: 90.9%, yield: 72.7%) as a light brown foam XH NMR (400 MHz, DMS0-d6) d PPM; 0.69 (3H, s), 1. 11 (3H, s), 2.13 (3H, s), 3.48 (2H, d, J = ll Hz), 3.58 (2H, d, J = ll Hz), 4.08 (2H, d, J = 4 Hz), 4.68 (1H, d, J = 14 Hz), 4.77 (1H, d, J = 14 Hz), 4.83 (1H, t, J = 4 Hz), 6.97 (1H, d, J = 6 Hz), 7.22- 7.32 (2H, m), 7.57-7.68 (2H, m), 8.20 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cmfx25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 15.2 minutes, enantiomeric excess: 84.2% ee (16b) A Optical Isomer sodium salt (Short in retention time) of 2- (((4 - ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 131 To a solution of ethanol (3 ml) of the optical isomer (short in retention time) of 2- (((4- ((5, 5-dimethyl-l, 3-dioxan-2-yl) methoxy) - 3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole (206 mg, content: 90.9%, 0.451 mmol) obtained in step (16a), IN was added aqueous sodium hydroxide solution (451 μl, 0.451 mmoles) at room temperature and the mixture was stirred for 15 minutes under the same conditions. After the reaction mixture was concentrated and ethanol was added to the residue, the mixture was subjected to azeotropic distillation and suspended with diethyl ether. The suspension was ultrasonically treated and allowed to stand. The supernatant liquid was removed and then the residue was dried to obtain the title compound (126 mg, 63.9% yield) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 0.69 (3H, s), 1. 11 (3H, s), 2.17 (3H, s), 3.48 (2H, d, J = ll Hz), 3.58 (2H, d, J = ll Hz), 4.06 (2H, d, J = 4 Hz), 4.36 (1H, d, J = 13 Hz), 4.81 (1H, d, J = 13 Hz), 4.83 (1H, t, J = 4 Hz), 6.79-6.87 (2H, m), 6.93 (1H, d, J = 6 Hz), 7.37-7.46 (2H, m), 8.25 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cmfx25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Results of analysis): retention time: 15.8 minutes, enantiomeric excess: 85.0% ee specific rotation: aD26'3 = + 116.94 (c = 0.5, EtOH) Example 17 Sodium salt of an optical isomer (Short in retention time ) of sodium salt of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 132 (17a) Optical Isomer (Short in retention time) of 2- (((3-methy1-4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinil ) -lH-benzimidazole Formula HA a solution of toluene (dehydrated) (1.5 ml) -water (1.47 μl, 81.5 μmol) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) thio) -1H-benzimidazole (300 mg, 679 mmol) separately obtained in In the same manner as described in steps (10a) to (10d) of Example 10, L - (+) diethyl tartrate (51.2 μl, 299 μmol) was added and the mixture was stirred at 50 ° C for 5 minutes at an atmosphere of nitrogen. Titanium (IV) isopropoxide (40.1 μl, 136 μmol) was added and the resulting mixture was stirred for an additional hour. Then it was cooled on ice and N, N-diisopropylethylamine (37.8 μl, 217 μmol) was added, and eumeno hydroperoxide (376 μl, 2.04 mmol according to the content was estimated as 80%) was added dropwise under a nitrogen atmosphere, The mixture was stirred at 0 ° C at room temperature for 5.5 hours. After a saturated aqueous solution of sodium hydrogen carbonate was added, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate / methanol) to obtain the title compound (256 mg, yield: 82.4%) as a light yellow foam. XH NMR (400 MHz, CDC13) d PPM; 1.85 (2H, t, J = 5 Hz), 2. 01 (2H, t, J = 5 Hz), 2.12-2.21 (1H, m), 2.21 (3H, s), 3.66-3.78 (4H, m), 3.86 (2H, dd, J = 4, 12 Hz) , 4.06-4.24 (4H, m), 4.64 (1H, d, J = 14 Hz), 4.83 (1H, d, J = 14 Hz), 6.77 (1H, d, J = 6 Hz), 7.26-7.40 ( 2H, m), 7.50-7.80 (2H, br), 8.32 (1H, d, J = 6 Hz). (17b) Sodium salt of Optical Isomer (Short in retention time) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl ) methyl) sulfinyl) -lH-benzimidazole Formula 134 To a solution of ethanol (10 ml) of the optical isomer (short in retention time) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (256 mg, 599 μmol) obtained in step (17a), IN was added aqueous sodium hydroxide solution (559 μl, 559 μmol) at room temperature, which was stirred for 30 minutes. After the mixture was concentrated and ethyl ether was added to the residue, the mixture was treated ultrasonically. The generated solid was collected by filtration in a nitrogen atmosphere. The solid was dried under reduced pressure to obtain the title compound (147 mg, yield: 54.8%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.74-1.86 (4H, m), 2.08-2.23 (lH, m), 2.18 (3H, s), 3.50-3.62 (4H, m), 3.76-3.84 (2H, m), 4.02 (2H, dd, J = 4, 12 Hz), 4.11 (2H, d, J = 7 Hz), 4. 37 (1H, d, J = 13 Hz), 4.81 (1H, d, J = 13 Hz), 6.80-6.92 (2H, m), 6.93 (1H, d, J = 6 Hz), 7.38-7.48 (2H , m), 8.25 (1H, d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 29.6 minutes, enantiomeric excess: 85.8% ee Example 18 Sodium salt of an optical isomer (Length in Retention Time) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 135 (18a) Optical Isomer (Length in Retention Time) of 2- (((3-methyl-4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinil -lH-benzimidazole Formula 136 To a solution of toluene (dehydrated) (1.5 ml) -water (1.35 μl, 74.8 μmol) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) thio) -1H-benzimidazole (150 mg, 340 mmol), separately obtained in the same manner as described in steps (10a) to (10d) of Example 10, D - (-) - diethyl tartrate (51.2 μl, 299 μmol) was added and the mixture was stirred at 50 ° C for 5 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (44.2 μl, 150 μmol) was added and the resulting mixture was stirred for an additional hour. After the mixture was cooled on ice, N, N-diisopropylethylamine (39.1 μl, 224 μmol) was added, and eumeno hydroperoxide (188 μl, 1.02 mmol according to the content was estimated as 80%) was added by dripping into a nitrogen atmosphere, the mixture was stirred at 0 ° C at room temperature for 7 hours. After a saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, the solvent was distilled off under reduced pressure. The residue obtained was purified by silica gel column chromatography (NH silica gel, solvent elution: ethyl acetate / methanol) to obtain the title compound (68 mg, yield: 43.7%) as a light yellow foam. XH NMR (400 MHz, CDC13) d PPM; 1.85 (2H, t, J = 5 Hz), 2. 01 (2H, t, J = 5 Hz), 2.12-2.22 (ÍH, m), 2.21 (3H, s), 3.66-3.78 (4H, m), 3.89 (2H, dd, J = 4, 12 Hz) , 4.06-4.26 (4H, m), 4.65 (1H, d, J = 14 Hz), 4.83 (1H, d, J = 14 Hz), 6.79 (1H, d, J = 6 Hz), 7.28-7.42 ( 2H, m), 7.50-7.80 (2H, br), 8.33 (1H, d, J = 6 Hz). (18b) Optical Isomer Sodium Salt (Retention Time Length) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) ) methyl) sulfinyl) -lH-benzimidazole Formula 137 To a solution of ethanol (10 ml) of the optical isomer (long retention time) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2 -yl) methyl) sulfinyl) -lH-benzimidazole (68 mg, 149 μmol) obtained in step (18a), was added IN aqueous sodium hydroxide (149 μl, 149 μmoles) at room temperature, which was stirred for 30 minutes. After the mixture was concentrated and ethyl ether was added to the residue, the mixture was treated ultrasonically. The resulting solid was collected by filtration in a nitrogen atmosphere. The solid was dried under reduced pressure to obtain the title compound (36 mg, yield: 54.8%) as a light yellow solid. * H NMR (400 MHz, DMSO-dg) d PPM; 1.77 (2H, t, J = 6 Hz), 1.83 (2H, t, J = 6 Hz), 2.08-2.23 (HH, m), 2.17 (3H, s), 3.50-3.60 (4H, m), 3.76 -3.86 (2H, m), 4.02 (2H, dd, J = 4, 12 Hz), 4.1K2H, d, J = 7 Hz), 4.37 (1H, d, J = 13 Hz), 4.81 (1H, d , J = 13 Hz), 6.85 (2H, dd, J = 3, 6 Hz), 6.93 (1H, d, J = 6 Hz), 7.42 (1H, dd, J = 3, 6 Hz), 8.26 (1H , d, J = 6 Hz). HPLC: (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 36.7 minutes, enantiomeric excess: 36% ee Example 19 Sodium salt of an optical isomer (Length in Retention Time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -IH- benzimidazole Formula 131 (19a) Optical Isomer (Length in Retention Time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -lH-benzimidazole Formula 139 To a suspension of toluene (dehydrated) (2.22 ml) -water (2.3 μl, 0.128 mmol) solution of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) 3,5-dimethylpyridin-2-ylmethyl) thio) -lH-benzimidazole (444 mg, 1.07 mmol) separately obtained in the same manner as described in steps (lia) to (llg) of Example 11 and D- ( -) -dietil tartrate (80.6 μl, 0.471 mmol) was stirred at 50 ° C for 10 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (63.2 μl, 0.214 mmol) was added and the resulting mixture was stirred for one more hour in the same conditions. After the mixture was cooled to room temperature and N, N-diisopropylethylamine (59.6 μl, 0.342 mmol) was added, the resulting mixture was cooled to 0 ° C. Then eumeno hydroperoxide (611 μl, 3.31 mmol) was added dropwise according to the content was estimated as 80%) for 5 minutes from 0 ° C to 2 ° C, the mixture was stirred at 0 ° C to 7 ° C for 3 hours and 35 minutes in a nitrogen atmosphere. After a saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 20 g, eluting solvent: dichloromethane, dichloromethane / methanol = 20 / l). Fractions containing the title compound were collected with ethyl acetate and concentrated to obtain the title compound (388 mg, yield: 84.4%) as a colorless foam. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.32 (3H, s), 1.36 (3H, s), 2.02-2.13 (lH, m), 2.16 (3H, s), 2.20 (3H, s), 3.74-3.85 (4H, m), 4.00 (2H, dd, J = 4, 12 Hz), 4.70 (1H, d, J = 14 Hz), 4.79 (1H, d, J = 14 Hz), 7.26-7.34 (2H, m), 7.59-7.70 (2H, m ), 8.18 (ÍH, s). HPLC: (Conditions) column: CHIRALPAK AD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = l / l (v / v), flow rate: 0.6 ml / mm, Detection: UV (254 nm) ( Results of analysis): retention time: 17.8 minutes, excess of enantiomer: 94.4% ee (19b) Optical Isomer sodium salt (Long in Retention Time) of 2- (((4- ((2,2-dimethyl) -l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 140 To a solution of ethanol (10 ml) of the optical isomer (long in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3, 5-dimethylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (379 mg, 0.882 mmol) obtained in step (19a), IN was added aqueous sodium hydroxide solution (878 μl, 0.882 mmol according to the concentration it was estimated as 1.004 M) at room temperature and the mixture was concentrated. The residue was subjected to azeotropic distillation with ethanol. The residue was suspended in diethyl ether, treated ultrasonically, concentrated to obtain the title (365 mg, yield: 91.7%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.03-2.13 (lH, m), 2.20 (3H, s), 2.21 (3H, s), 3.76-3.88 (4H, m), 4.00 (2H, dd, J = 4, 12 Hz), 4.38 (ΔH, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.81-6.90 (2H, m), 7.40-7.47 (2H, m ), 8.23 (1H, s). HPLC: (Conditions) column: CHIRALPAK AD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = l / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 17.0 minutes, excess enantiomer: 94.9% ee specific rotation: aD27'4 = -76.29 (c = 0.5, EtOH) Example 20 Sodium salt of an optical isomer (Short in retention time) of 2- (((4- (2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) ) methyl) sulfinyl) -lH-benzimidazole Formula 141 (20a) Optical Isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -lH-benzimidazole Formula 142 To a suspension of toluene (dehydrated) (2.96 ml) -water (3.09 μl, 0.172 mmol) of 2- (((4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) - 3,5-dimethylpyridin-2-y1) methyl) thio) -1H-benzimidazole (591 mg, 1.43 mmol) separately obtained in the same manner as described in steps (lia) to (llg) of Example 11 and tartrate of L- (+) diethyl (108 μl, 0.629 mmol) was stirred at 50 ° C for 5 minutes in a nitrogen atmosphere. Titanium (IV) isopropoxide (84.4 μl, 0.286 mmole) was added and the resulting mixture was stirred for one hour under the same conditions. After the mixture was cooled to room temperature and N, N-diisopropylethylamine (79.7 μL, 0.458 mmol) was added, the resulting mixture was cooled to 0 ° C. After eumeno hydroperoxide (816 μl, 4.42 mmoles according to the content was estimated as 80%) was added by dripping for 10 minutes from 0 ° C to 1 ° C, the mixture was stirred for 3 hours and 10 minutes under the same conditions. After a saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate anhydrous, filtered, and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 20 g, eluting solvent: dichloromethane, dichloromethane / methanol = 20 / l). Fractions containing the title compound were collected with ethyl acetate and concentrated to obtain the title compound (498 mg, yield: 81.1%) as a colorless foam. X NMR (400 MHz, DMSO-d6) d PPM; 1.32 (3H, s), 1. 36 (3H, s), 2.02-2.12 (ÍH, m), 2.16 (3H, s), 2.20 (3H, s), 3.74-3.84 (4H, m), 4.00 (2H, dd, J = 4, 12 Hz), 4.70 (1H, d, J = 14 Hz), 4.79 (1H, d, J = 14 Hz), 7.26-7.34 (2H, m), 7.58-7.70 (2H, m), 8.18 (ÍH, s). HPLC: (Conditions) column: CHIRALPAK AD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = l / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) (Analysis results): retention time: 14.6 minutes, excess enantiomer: 95.4% ee (20b) Optical Isomer sodium salt (Short in retention time) of 2 - (((4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 143 To a solution of ethanol (10 ml) of the optical isomer (short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3, 5-dimethylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole (480 mg, 1.12 mmol) obtained in step (20a), IN was added aqueous sodium hydroxide solution (1.12 ml, 1.12 mmol according to the concentration it was estimated as 1.004 M) at room temperature and the mixture was concentrated. The residue was subjected to azeotropic distillation with ethanol. The residue was suspended in diethyl ether, the suspension was treated ultrasonically, concentrated to obtain the title compound (447 mg, yield: 88.4%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1. 36 (3H, s), 2.03-2.14 (ÍH, m), 2.21 (6H, s), 3.76-3.87 (4H, m), 4.00 (2H, dd, J = 4, 12 Hz), 4.39 (1H, d, J = 13 Hz), 4.74 (1H, d, J = 13 Hz), 6.82-6.90 (2H, m), 7.40-7.48 (2H, m), 8.23 (1H, s). HPLC: (Conditions) column: CHIRALPAK AD-H (manufactured by Daicel Chemical Industries Ltd.) (0.46 cm [phi] * 25 cm), eluent: hexane / ethanol = l / l (v / v), flow rate: 0.6 ml / min, Detection: UV (254 nm) ( Test results): retention time: 14.4 minutes, enantiomeric excess: 95.4% ee Example 21 2- (((4- (6,10-dioxaspiro [4.5] dec-8-ylmethoxy) -3-methylpyridin sodium salt -2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 144 (21a) 6, 10-dioxaspiro [4.5] dec-8-ylmethanol Formula 145 The same procedure of step (7a) of Example 7 was repeated using 2- (hydroxymethyl) -1,3-propanediol and cyclopentanone to obtain the title compound (2.8 g, yield: 87%) as a yellow oil.

XH NMR (400 MHz, CDC13) d PPM; 1.51-1.55 (ÍH, m), 1.62-1.72 (4H, m), 1.83-1.94 (4H, m), 3.73-3.80 (4H, m), 3.99 (2H, dd, J = 4, 12 Hz). (21b) 2- (((4- (6,10-dioxaspiro [4.5] dec-8-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole sodium salt Formula 146 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 6, 10-dioxaspiro [4.5] dec-8-ylmethanol obtained in step (21a) to obtain the title compound (180 mg, total yield: 8.1%) as a light yellow solid. X H NMR (400 MHz, DMS0-d 6) d PPM; 1.52-1.62 (4H, m), 1. 75-1.86 (4H, m), 2.08-2.16 (ÍH, m), 2.17 (3H, s), 3.72-3.82 (2H, m), 3.92-4.02 (2H, m), 4.09 (2H, d, J = 7 Hz), 4.36 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 6.83 (2H, dd, J = 3, 6 Hz), 6. 93 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.27 (1H, d, J = 6 Hz).

Example 22 Sodium salt of 2- (((4- (5,9-dioxaspiro [3.5] non-7-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 147 The same procedure as in steps (21a) and (21b) of Example 21 was repeated using 2- (hydroxymethyl) -1,3-propanediol and cyclobutanone to obtain the title compound (265 mg, total yield: 6.2%) as a light yellow solid. 1R NMR (400 MHz, DMSO-d6) d PPM; 1.58-1.70 (2H, m), 2. 06-2.22 (5H, m), 2.17 (3H, s), 3.66-3.76 (2H, m), 3.86- 3.96 (2H, m), 4.07 (2H, d, J = 6 Hz), 4.37 (1H, d, J = 13 Hz), 4. 79 (1H, d, J = 13 Hz), 6.85 (2H, dd, J = 3, 6 Hz), 6.93 (1H, d, J = 6 Hz), 7.44 (2H, dd, J = 3, 6 Hz ), 8.26 (1H, d, J = 6 Hz). EXAMPLE 23 Sodium salt of 2- (((4- ((2,2-diethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole Formula 148 (23a) (2,2-diethyl-l, 3-dioxan-5-yl) methanol Formula 149 The same procedure of step (7a) of Example 7 was repeated using 2- (hydroxymethyl) -1,3-propanediol, and 3-pentanone to obtain the title compound (1.5 g, yield: 46%) as a light yellow oil . XH NMR (400 MHz, CDC13) d PPM; 0.87 (3H, t, J = 7 Hz), 0.88 (3H, t, J = 7 Hz), 1.46-1.51 (ÍH, m), 1.70 (2H, q, J = 7 Hz), 1.78 (2H, q , J = 7 Hz), 3.70-3.88 (4H, m), 3.96-4.10 (2H, m). (23b) Sodium salt of 2- (((4- ((2,2-diethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H- benzimidazole Formula 150 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using (2,2-diethyl-1,3-dioxan-5-yl) methanol obtained in step (23a) to obtain the compound of title (164 mg, total yield: 9.7%) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.80 (6H, t, J = 7 Hz), 1.63 (2H, q, J = 7 Hz), 1.70 (2H, q, J = 7 Hz), 2.01-2.12 (ÍH, m), 2.18 (3H, s ), 3.50-3.80 (2H, m), 3.94-4.20 (2H, m), 4.12 (2H, d, J = 7 Hz), 4.37 (1H, d, J = 13 Hz), 4.81 (1H, d, J = 13 Hz), 6.84 (2H, dd, J = 3, 6 Hz), 6.92 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz). Example 24 Sodium salt of 2- (((3-methyl-4- ((1-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2-yl) methyl sulfinyl) -lH-benzimidazole Formula 151 (24a) (1-methyl-2,6,6-trioxabicyclo [2. 2. 2] oct-4-yl) methanol Formula 152 A mixture of pentaerythritol (15 g, 110 mmol), ethyl orthoacetate (20.2 ml, 110 mmol), and p-toluenesulfonic acid monohydrate (947 mg, 5.5 mmol) was stirred at 100 ° C for 30 minutes. The temperature of the mixture was further elevated to 130 ° C and the mixture was stirred for 30 minutes. To the reaction mixture, triethylamine (1.53 ml, 11 mmol) was added and the reaction mixture was concentrated. The residue was purified by silica gel column chromatography (eluant solvent: heptane / ethyl acetate) to obtain the title compound (8.5 g, yield: 48.2%) as a light yellow solid. XH NMR (400 MHz, CDC13) d PPM; 1.47 (3H, s), 3.46 (2H, d, J = 4 Hz), 4.02 (6H, s). (24b) 2, 3-dimethyl-4- ((1-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridine-oxide Formula 153 To a solution of dimethisulfoxide (30 ml) of (1-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methanol (4.5 g, 28.1 mmol) obtained in step (24a) was added sodium hydride, in oil (1.29 g, 29.5 mmoles depending on the content was estimated as 55%) at room temperature. To the mixture, 4-chloro-2,3-dimethylpyridine-oxide (3.99 g, 25.3 mmol) was added, which was stirred at 60 ° C for 3 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate / methanol) to obtain the title compound (7.46 g, yield: 81%) as a yellow oil. X NMR (400 MHz, CDC13) d PPM; 1.50 (3H, s), 2.20 (3H, s), 2.54 (3H, s), 3.77 (2H, s), 4.15 (6H, s), 6.53 (1H, d, J = 6 Hz), 8.14 (HI) , d, J = 6 Hz). (24c) (3-Methyl-4- ((1-methyl-2, 6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2-yl) methanol Formula 154 A mixture of 2,3-dimethyl-4- ((1-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridine 1-oxide (6.4 g, 22.8 mmol) obtained in step (24b) and acetic anhydride (20 ml) was stirred at 80 ° C for one hour. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. To the residue, methanol (30 ml) and 5N of aqueous sodium hydroxide solution (10 ml) were added and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated and ethyl acetate was added to the residue. The mixture was washed with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting residue (solid) was washed with diethyl ether and collected by filtration to obtain the title compound (1.5 g, yield: 28.7%) as a yellow solid. Xl NMR (400 MHz, CDC13) d PPM; 1.50 (3H, s), 2.04 (3H, s), 3.80 (2H, s), 4.15 (6H, s), 4.65 (2H, s), 4.77 (1H, br s), 6.60 (1H, d, J = 6 Hz), 8.29 (1H, d, J = 6 Hz). (24d) 2- (((3-met il-4- ((1-methyl-2,6,6-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2-yl) methyl) thio ) - lH-benzimidazole Formula 155 To a tetrahydrofuran solution (dehydrated, 20 ml) of (3-methyl-4- ((1-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2-yl) methanol (0.37 g, 1.32 mmol) obtained in step (24c) and triethylamine (0.368 ml), 2.64 mmole), methanesulfonyl chloride (153 μl, 1.98 mmol) was added dropwise under a nitrogen atmosphere of 1 ° C to 4 ° C. The resulting mixture was stirred under the same conditions for 1.5 hours. In addition, 2-mercaptobenzimidazole (204 mg, 1.52 mmol) was added to the mixture and stirred at room temperature for 18 hours. After the reaction mixture was concentrated, the residue was purified by silica gel column chromatography (solvent elution: ethyl acetate / methanol) to obtain the title compound (230 mg, yield: 40.9%) as a light yellow foam. . Xl NMR (400 MHz, CDC13) d PPM; 1.50 (3H, s), 2.27 (3H, s), 3.80 (2H, s), 4.15 (6H, s), 4.38 (2H, s), 6.65 (1H, d, J = 6 Hz), 7.15-7.21 (2H, m), 7.36-7.68 (2H, m), 8.35 (1H, d, J = 6 Hz). (24e) 2- (((3-methyl-4- ((1-methyl-2, 6,7- trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 156 To a solution of toluene-methanol (10: 1) (20 ml) of 2- (((3-methyl-4- ((l-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4- il) methoxy) pyridin-2-yl) methyl) thio) -lH-benzimidazole (230 mg, 556 μmol) obtained in step (24d), was added dropwise to a toluene-methanol (10: 1) solution ( 5 ml) of 3-chloroperbenzoic acid (133 mg, 0.5 mmol according to the content was estimated as 65%) in a nitrogen atmosphere of -50 ° C to -60 ° C for 5 minutes and the mixture was stirred under the same conditions for 3.5 hours. To the reaction mixture, a saturated aqueous sodium acid carbonate solution was added, which was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (NH silica gel, eluting solvent: ethyl acetate / methanol) to obtain the title compound (143 mg, yield: 59.9%) as a light yellow foam. Xl NMR (400 MHz, CDC13) d PPM; 1.50 (3H, s), 2.17 (3H, s), 3.76 (2H, s), 4.12 (6H, s), 4.63 (1H, d, J = 14 Hz), 4.79 (1H, d, J = 14 Hz), 6.60 (1H, d, J = 6 Hz), 7.30-7.38 (2H, m), 7.47-7.56 (1H, m), 7.76-7.86 (ÍH, m), 8.30 (1H, d, J = 6 Hz), 11.05 (1H, br s). (24f) Sodium salt of 2- (((3-methyl-4- ((1-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -IH-benzimidazole Formula 157 To a solution of ethanol (5 ml) of 2- (((3-methyl-4- ((l-methyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) pyridin-2 -yl) methyl) sulfinyl) -lH-benzimidazole (143 mg, 333 μmol) obtained in step (24e), IN was added aqueous sodium hydroxide solution (333 μl, 333 μmol) was added at room temperature and the mixture was stirred for 0.5 hours. The mixture was concentrated and the residue was dissolved in ethanol. Then, ethyl ether was added to the solution, and sonic. The generated solid was filtered under a nitrogen atmosphere and dried under reduced pressure to obtain the title compound (150 mg, yield: 100%) as a light yellow solid. X NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 2. 19 (3H, s), 3.92 (2H, s), 4.04 (6H, s), 4.35 (1H, d, J = 15 Hz), 4.82 (1H, d, J = 15 Hz), 6.82-6.87 (3H , m), 7.42 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz). EXAMPLE 25 Sodium salt of 2- (((4- (1,5-dioxaspiro [5.5] undec-3-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 158 (25a) 1,5-dioxaspiro [5.5] undec-3-ylmethanol Formula 159 The same procedure of step (la) of Example 1 was repeated using 2- (hydroxymethyl) -1,3-propanediol and cyclohexanone to obtain the title compound (2.26 g, yield: 65%) as a light yellow oil. X NMR (400 MHz, CDC13) d PPM; 1.37-1.46 (2H, m), 1.47-1.57 (4H, m), 1.68-1.76 (2H, m), 1.77-1.90 (3H, m), 3.74-3.8K4H, m), 4.02 (2H, dd, J = 4, 12 Hz). Sodium salt of (25b) 2 - (((4- (1, 5-dioxaspiro [5.5] undec-3-ylmethoxy) -3-methylpyridin-2- iljmetil) sulfinyl) -lH-benzimidazole Formula 160 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 1,5-dioxaspiro [5.5] undec-3-ylmethanol obtained in step (25a) to obtain the title compound (125 mg, total yield: 8.4%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.30-1.48 (6H, m), 1. 64-1.76 (4H, m), 2.06-2.15 (HH, m), 2.18 (3H, s), 3.73- 3.82 (2H, m) 3.96-4.03 (2H, m), 4.11 (2H, d, J = 7 Hz), 4.44 (1H, d, J = 13 Hz), 4.8K1H, d, J = 13 Hz), 6.90-6.98 (3H, m), 7.47 (2H, dd, J = 3, 6 Hz), 8.25 (1H, d, J = 6 Hz). EXAMPLE 26 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) oxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 161 The same procedure as in steps (6d), (6e) and (6f) of Example 6 was repeated using 2,2-dimethyl-1,3-dioxan-5-ol obtained in step (9a) to obtain the title compound (530 mg, total yield: 18%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.34 (3H, s), 1. 40 (3H, s), 2.23 (3H, s), 3.79 (2H, dd, J = 3, 12 Hz), 4.12 (2H, dd, J = 3, 12 Hz), 4.39 (1H, d, J = 13 Hz), 4.46-4.54 (HH, m), 4.82 (1H, d, J = 13 Hz), 6.86-6.94 (3H, m), 7.42-7. 8 (2H, m), 8.23 (1H, d, J = 6 Hz). EXAMPLE 27 Sodium salt of 2- (((4- (1,4-dioxaspiro [4.5] dec-8-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 162 (27a) 1, 4-dioxaspiro [4.5] decan-8-ol Formula 163 It was repeated the same way as in Example 9a using 1,4-cyclohexanedione monoethylene ketal to obtain the title compound (2.6 g, yield: 79%) as a light yellow oil. XH NMR (400 MHz, CDC13) d PPM; 1.53-1.71 (4H, m), 1.77-1.93 (4H, m), 3.75-3.85 (ÍH, m), 3.93-3.96 (4H, m). Sodium salt of (27b) 2 - (((4- (l, 4-dioxaspiro [4.5] dec-8-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole Formula 164 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 1,4-dioxaspiro [4.5] decan-8-ol obtained in step (27a) to obtain the title compound (230 mg, total yield: 7.3%) as a light yellow solid. X NMR (400 MHz, DMS0-d6) d PPM; 1.57-1.94 (8H, m), 2. 17 (3H, s), 3.87 (4H, s), 4.35 (1H, d, J = 13 Hz), 4.62-4.68 (HI, m), 4.79 (1H, d, J = 13 Hz), 6.84 (2H , dd, J = 3, 6 Hz), 6.97 (1H, d, J = 6 Hz), 7.43 (2H, dd, J = 3, 6 Hz), 8.23 (1H, d, J = 6 Hz).

EXAMPLE 28 Sodium salt of 2- (((4- (2- (2,2-dimethyl-l, 3-dioxan-5-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1 H -benzimidazole Formula 165 (28a) 2- (2, 2-dimethyl-l, 3-dioxan-5-yl) ethanol Formula 166 To a solution of acetone (30 ml) of 2- (hydroxymethyl) butan-1,4-diol (3.4 g, 28.3 mmol) obtained according to the method described in J. Med. Chem., 30 (9), 1636-1642 (1987), p-toluenesulfonic acid monohydrate (244 mg, 2.83 mmol) was added at room temperature and the mixture was stirred for 15 hours. To the reaction mixture was added triethylamine (394 μL, 2.83 mmol) and the mixture was concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane / ethyl acetate) to obtain the title compound (1.0 g, yield: 22%) as a light yellow oil.

X NMR (400 MHz, CDC13) d PPM; 1.42 (6H, s), 1.54-1.62 (2H, m), 1.90-2.02 (HH, m), 3.58-3.76 (4H, m), 3.94 (2H, dd, J = 4, 12 Hz). (28b) Sodium salt of 2- (((4- (2- (2,2-dimethyl-1,3-dioxan-5-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) - Benzimidazole Formula 167 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 2- (2,2-dimethyl-1,3-dioxan-5-yl) ethanol obtained in step (28a) to obtain the compound of the title (58 mg, total yield: 2.0%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.28 (3H, s), 1. 34 (3H, s), 1.64-1.72 (2H, m), 1.83-1.92 (ÍH, m), 2.16 (3H, s), 3.54-3.63 (2H, m), 3.83 (2H, dd, J = 4 , 16 Hz), 4.06 (2H, t, J = 6 Hz), 4.38 (1H, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.85 (2H, dd, J = 3, 6 Hz), 6.91 (1H, d, J = 6 Hz), 7.43 (2H, dd, J = 3, 6 Hz), 8. 26 (1H, d, J = 6 Hz).

EXAMPLE 29 Sodium salt of 2- (((4- ((1-ethyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) - benzimidazole Formula 168 (29a) (1-ethyl-2,6,6-trioxabicyclo [2.2.2] oct-4-yl) methanol Formula 169 The same manner as in Example 24 was repeated using triethyl ortho propionate (15 g, 110 mmol) to obtain the title compound (14 g, yield: 73%) as a light yellow oil. Xl NMR (400 MHz, CDC13) d PPM; 0.96 (3H, t, J = 7 Hz), 1.71 (2H, q, J = 7 Hz), 3.47 (2H, d, J = 4 Hz), 4.02 (6H, s). (29b) Sodium salt of 2- (((4- ((1-ethyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) -3-methylpyridin-2-yl) methyl sulfinyl) -benzimidazole Formula 170 The same manner as in Example 24 was repeated using (l-ethyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methanol obtained in step (29a) to obtain the title compound (145 mg , total yield: 1.7%) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.86 (3H, t, J = 7 Hz), 1.59 (2H, q, J = 7 Hz), 2.19 (3H, s), 3.92 (2H, s), 4.04 (6H, s), 4.35 (1H, d) , J = 13 Hz), 4.82 (1H, d, J = 13 Hz), 6.80-6.90 (3H, m), 7.42 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz) Example 30 Sodium salt of 2- (((3-methyl-4- (2- (2-methyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) - benzimidazole Formula 171 [30a) 2- (2-methyl-l, 3-dioxan-2-yl) ethanol Formula 172 The same procedure as in steps (8a) and (8b) of Example 8, was repeated using ethyl acetoacetate to obtain the title compound (5.4 g, total yield: 49%) as a light yellow oil. Xl NMR (400 MHz, CDC13) d PPM; 1.49 (3H, s), 1.91 (2H, t, J = 6 Hz), 1.90-2.40 (2H, m), 3.00 (1H, t, J = 6 Hz), 3.80-4.06 (6H, m). (30b) 2- (((3-Methyl-4- (2- (2-methyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 173 The same procedure as in steps (8c) to (8g) of Example 8, was repeated using 2- (2-methyl-l, 3-dioxan-2-yl) ethanol obtained in step (30a) to obtain the compound of the title (113 mg, total yield: 2.5%) as a light yellow solid.

X H NMR (400 MHz, DMSO-d 6) d PPM; 1.39 (3H, s), 1.46-1.70 (2H, m), 2.12-2.19 (2H, m), 2.16 (3H, s), 3.76-3.90 (4H, m), 4. 11 (2H, t, J = 7 Hz), 4.38 (1H, d, J = 13 Hz), 4.79 (1H, d, J = 13 Hz), 6.82-6.92 (2H, m), 6.90 (1H, d, J = 6 Hz), 7.38-7.48 (2H, m), 8.24 (ÍH, d, J = 6 Hz). Example 31 Sodium salt of 2- (((4- (2- (5,9-dioxaspiro [3.5] non-7-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 174 The same form as in Example 28 was repeated using cyclobutanone to obtain the title compound (80 mg, total yield: 0.8%) as a light yellow solid. [0672] NMR (400 MHz, DMSO-d6) d PPM; 1.57-1.67 (4H, m), 1.86- 1.96 (1H, m), 2.05-2.18 (4H, m), 2.16 (3H, s), 3.40-3.50 (2H, m), 3.82 (2H, dd, J = 4, 11 Hz), 4.06 (2H, t, J = 7 Hz), 4.38 (1H, d, J = 13 Hz), 4.78 (1H, d, J = 13 Hz), 6.85 (2H, dd, J = 3, 6 Hz), 6. 90 (1H, d, J = 6 Hz), 7.43 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz).

Example 32 Sodium salt of 2- (((4- (1,3-dioxan-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 175 (32a) 2- ((benzyloxy) methyl) -1,3-dioxane Formula 176 A mixture of benzyloxyacetaldehyde (3.6 g, 24 mmol), 1,3-propanediol (5.2 ml, 72 mmol), triethyl orthoformate (4 ml, 24 mmol), and p-toluenesulfonic acid monohydrate (414 mg, 2.45 mmol) were added. stirred at room temperature for 17 hours. To the reaction mixture, triethylamine (669 μl, 4.8 mmol) was added, which was concentrated. The residue was purified by silica gel column chromatography (eluant solvent: heptane / ethyl acetate) to obtain the title compound (2.9 g, yield: 58%) as a light yellow oil. X NMR (400 MHz, CDC13) d PPM; 1.22 (ÍH, t, J = 7 Hz), 2. 04-2.20 (lH, m), 3.49 (2H, d, J = 4 Hz), 3.80 (2H, dt, J = 2, 12 Hz), 4.14 (2H, dd, J = 5, 11 Hz), 4.59 (2H, s), 4.76 (1H, t, J = 4 Hz), 7.20-7.42 (5H, m). (32b) 1,3-dioxan-2-ylmethanol Formula 177 To a methanol solution (50 ml) of 2- ((benzyloxy) methyl) -1,3-dioxane (2.9 g, 13.9 mmol) obtained in step (32a), 10% palladium carbon (760 mg) was added. and the mixture was stirred at room temperature under a hydrogen atmosphere for 2 days. The reaction mixture was filtered through celite and washed with ethyl acetate. Next, the solvent of the filtrate was distilled under reduced pressure to obtain a crude product of the title compound (860 mg, yield: 52.4%) as a light yellow oil. XH NMR (400 MHz, CDC13) d PPM; 1.34-1.44 (ÍH, m), 1.86 (1H, t, J = 5 Hz), 2.04-2.20 (lH, m), 3.60 (2H, dd, J = 4, 6 Hz), 3.82 (2H, dt, J = 2, 12 Hz), 4.15 (2H, dd, J = 5, 11 Hz), 4.66 (1H, t, J = 5 Hz). (32c) Sodium salt of 2- (((4- (1,3-dioxan-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 178 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 1,3-dioxan-2-ylmethanol obtained in step (32b) to obtain the title compound (148 mg, total yield: 10 %) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33-1.42 (ÍH, m), 1. 84-1.98 (1H, m), 2.16 (3H, s), 3.74-3.84 (2H, m), 3.98- 4.08 (4H, m), 4.37 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 4. 92 (1H, t, J = 4 Hz), 6.84 (2H, dd, J = 3, 6 Hz), 6.91 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz ), 8.25 (1H, d, J = 6 Hz). EXAMPLE 33 Sodium salt of 2- (((3-methyl-4- ((2-methyl-1, 3-dioxan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 179 (33a) (2-methyl-l, 3-dioxan-2-yl) methanol Formula 180 The same procedure as in steps (32a) and (32b) of Example 32 was repeated using l-benzyloxy-2-propanone to obtain the title compound (1.51 g, total yield: 37%) as a light yellow oil. XH NMR (400 MHz, CDC13) d PPM; 1.43 (3H, s), 1.92-2.20 (2H, m), 3.53 (2H, d, J = 6 Hz), 3.86-4.06 (4H, m). (33b) 2- (((3-Methyl-4- ((2-methyl-1, 3-dioxan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 181 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using (2-methyl-1, 3-dioxan-2-yl) methanol obtained in step (33a) to obtain the title compound ( 220 mg, total yield: 8.6%) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.45 (3H, s), 1.57- 1.67 (2H, m), 2.19 (3H, s), 3.88 (4H, t, J = 6 Hz), 4.09 (2H, s), 4. 36 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 6.84 (2H, dd, J = 3, 6 Hz), 6.98 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.25 (1H, d, J = 6 Hz). EXAMPLE 34 Sodium salt of 2- (((3-methyl-4- (2- (2,5,5-trimethyl-1,3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinil ) -benzimidazole Formula 182 (34a) 2- (2, 5, 5-trimethyl-l, 3-dioxan-2-yl) ethanol Formula 183 The same procedure as in steps (8a) and (8b) of Example 8 was repeated using ethyl acetoacetate, and 2,2-dimethyl-1,3-propandiol to obtain the title compound (7.3 g, total yield: 55%) as a light yellow oil. Xl NMR (400 MHz, CDC13) d PPM; 0.81 (3H, s), 1.16 (3H, s), 1.44 (3H, s), 1.93 (2H, t, J = 6 Hz), 3.06 (1H, t, J = 6 Hz), 3.42 (2H, d , J = 12 Hz), 3.68 (2H, d, J = 12 Hz), 3.82-3.92 (2H, m). (34b) 2- (((3-Methyl-4- (2- (2, 5, 5-trimethyl-1, 3-dioxan-2-yl) ethoxy) pyridin-2-yl) methyl sodium salt) sulfinil) - Benzimidazole Formula 184 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 2- (2, 5, 5-trimethyl-1,3-dioxan-2-yl) ethanol obtained in step (34a) for obtain the title compound (196 mg, total yield: 7.2%) as a light yellow solid. X NMR (400 MHz, DMS0-d6) d PPM; 0.83 (3H, s), 0.94 (3H, s), 1.38 (3H, s), 2.12-2.20 (2H, m), 2.16 (3H, s), 3.39 (2H, d, J = ll Hz), 3.51 (2H, d, J = ll Hz), 4.13.2H, t, J = 3 Hz), 4.38 (1H, d, J = 13 Hz), 4.78 (1H, d, J = 13 Hz), 6.84 (2H , dd, J = 3, 6 Hz), 6.88 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 3, 6 Hz), 8.25 (1H, d, J = 6 Hz). EXAMPLE 35 Sodium salt of 2- (((3-methyl-4- (2- (6-methyl-5,7-dioxaspiro [2.5] oct-6-yl) ethoxy) pyridin-2-yl) methyl) sulfinil ) -benzimidazole Formula 185 (35a) 2- (6-methyl-5,7-dioxaspiro [2,5] oct-6-yl) ethanol Formula 186 The same procedure as in steps (8a) and (8b) of Example 8, was repeated using ethyl acetoacetate and 1,1-bis (hydroxymethylcyclopropane) to obtain the title compound (2.9 g, total yield: 36%) as a light yellow oil. Xl NMR (400 MHz, CDC13) d PPM; 0.38 (2H, t, J = 6 Hz), 0.62 (2H, t, J = 6 Hz), 1.54 (3H, s), 1.96 (2H, t, J = 6 Hz), 3.04 (1H, t, J = 6 Hz), 3.16 (2H, d, J = 12 Hz), 3.84-3.92 (2H, m), 4.20 (2H, d, J = 12 Hz). (35b) 2- (((3-Methyl-4- (2- (6-methyl-5,7,7-dioxaspiro [2.5] oct-6-yl) ethoxy) pyridin-2-yl) methyl sodium salt) sulfinyl) -benzimidazole Formula 187 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 2- (6-methyl-5,7-dioxaspiro [2.5] oct-6-yl) ethanol obtained in step (35a) to obtain the title compound (163 mg, total yield: 5.5%) as a light yellow solid. : H NMR (400 MHz, DMS0-d6) d PPM; 0.34-0.50 (4H, m), 1.46 (3H, s), 2.18 (3H, s), 2.22 (2H, t, J = 6 Hz), 3.45 (2H, d, J = ll Hz), 3.76 (2H , d, J = ll Hz), 4.16 (2H, t, J = 7 Hz), 4.39 (1H, d, J = 13 Hz), 4.78 (IH, d, J = 13 Hz), 6.86 (2H, dd , J = 3, 6 Hz), 6.91 (1H, d, J = 6 Hz), 7.43 (2H, dd, J = 3, 6 Hz), 8.26 (1H, d, J = 6 Hz). Example 36 Sodium salt of 2 - (((4- (2- (2- (methoxymethyl) -1, 3-dioxan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 188 (36a) 2- (2- (methoxymethyl) -1, 3-dioxan-2-yl) ethanol Formula 189 x HO The same procedure as in steps (8a) and (8b) of Example 8 was repeated using methyl 4-methoxyacetoacetate to obtain the title compound (4.5 g, total yield: 34%) as a light yellow oil.

X NMR (400 MHz, CDC13) d PPM; 1.58-1.70 (ÍH, m), 1.80-1.96 (1H, m), 2.03 (2H, t, J = 6 Hz), 2.86 (1H, t, J = 6 Hz), 3.43 (3H, s), 3.62 (2H, s), 3.76-3.84 (2H, m), 3.90-4.04 (4H, m). (36b) Sodium salt of 2- (((4- (2- (2- (methoxymethyl) -1, 3-dioxan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) - benzimidazole Formula 190 The same procedure as in steps (6b) to (6f) of Example 6 was repeated using 2- (2- (methoxymethyl) -1, 3-dioxan-2-yl) ethanol obtained in step (36a) to obtain the compound of the title (304 mg, total yield: 7.0%) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.50-1.70 (2H, m), 2. 16 (3H, s), 2.20 (2H, t, J = 7 Hz), 3.29 (3H, s), 3.52 (2H, s), 3. 80-3.90 (4H, m), 4.09 (2H, t, J = 7 Hz), 4.37 (1H, d, J = 13 Hz), 4. 78 (1H, d, J = 13 Hz), 6.83 (2H, dd, J = 3, 6 Hz), 6.87 (1H, d, J = 6 Hz), 7.41 (2H, dd, J = 3, 6 Hz ), 8.25 (1H, d, J = 6 Hz). EXAMPLE 37 Sodium salt of 2- (((4- ((1-cyclopropyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 191 (37a) Methyl cyclopropanecarboxyimidate hydrochloride Formula 192 0 'r NH HCI To a mixture of cyclopropanecarbonitrile solution (15 g, 224 mmol), diethyl ether (200 ml), and methanol (10 ml), acid chloride was injected under cooling with ice and the mixture was stirred at room temperature for 17 hours. After the solvent in the reaction mixture was distilled under reduced pressure, ethyl ether was added to the residue and the generated solid was collected by filtration under nitrogen atmosphere to obtain the title compound (29 g, yield: 95.5%) as a solid. light yellow. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.10-1.24 (4H, m), 2. 06-2.38 (1H, m), 3.99 (3H, s), 10.8 (1H, br s), 12.1 (1H, br s). (37b) (trimethoxymethyl) cyclopropane Formula 193 To a solution of n-hexane (75 ml) of methyl cyclopropanecarboxyimidate hydrochloride (17.4 g, 128 mmol) obtained in step (37a), methanol (25.9 ml, 640 ml) was added and the mixture was stirred at room temperature for 3.5 days. The precipitate of ammonium chloride was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a crude product of the title compound (7.5 g, yield: 40%) as a light yellow oil. XH NMR (400 MHz, CDC13) d PPM; 0.47-0.56 (2H, m), 0.58-0.67 (2H, m), 0.84-0.94 (ÍH, m), 3.29 (9H, s). (37c) (1-cyclopropyl-2,6,6-trioxabicyclo [2.2.2] oct-4-yl) methanol Formula 194 The same procedure of step (24a) of Example 24 was repeated using (trimethoxymethyl) cyclopropane (9.8 g, 67. 2 mmole) obtained in step (37b) to obtain the title compound (11.9 g, yield: 95%) as a light yellow oil.

Xl NMR (400 MHz, CDC13) d PPM; 0.42-0.52 (2H, m), 0.58-0.68 (2H, m), OR .86-0.96 (ÍH, m), 3.46 (2H, s), 4.02 (6H, s). (37d) Sodium salt of 2- (((4- ((1-cyclopropyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) -3-methylpyridin-2-yl) methyl Sulfinyl) -benzimidazole Formula 195 The same procedure as in steps (24b) a (24f) of Example 24 was repeated using (1-cyclopropyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methanol obtained in step (37c) above to obtain the title compound (147 mg , total yield: 3.2%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 0.35-0.54 (4H, m), 1.06-1.18 (HH, m), 2.19 (3H, s), 3.92 (2H, s), 4.04 (6H, s), 4.38 (1H, d, J = 13 Hz) , 4.80 (1H, d, J = 13 Hz), 6.82-6.94 (3H, m), 7.44 (2H, dd, J = 3, 6 Hz), 8.27 (1H, d, J = 6 Hz). EXAMPLE 38 Sodium salt of 2- (((4- ((1-cyclobutyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 196 (38a) (1-cyclobutyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methanol Formula 197 The same procedure as in steps (37a) to (37c) of Example 37 was repeated using cyclobutanecarbonitrile to obtain the title compound (15 g, total yield: 51%) as a light yellow oil. Xl NMR (400 MHz, CDC13) d PPM; 1.70-2.30 (7H, m), 3.47 (2H, s), 4.03 (6H, s). (38b) Sodium salt of 2- (((4- ((1-cyclobutyl-2,6,7-trioxabicyclo [2.2.2] oct-4-yl) methoxy) -3-methylpyridin-2-yl) methyl Sulfinyl) -benzimidazole Formula 198 The same procedure as in steps (24b) to (24f) of Example 24 was repeated using (1-cyclobutyl- 2,6,6-trioxabicyclo [2.2.2] oct-4-yl) methanol obtained in step (38a) above to obtain the title compound (56 mg, 2.3%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.60-1.86 (4H, m), 1.94-2.07 (3H, m), 2.19 (3H, s), 3.92 (2H, s), 4.05 (6H, s), 4.33 (1H, d, J = 13 Hz) , 4.83 (1H, d, J = 13 Hz), 6.78-6.90 (3H, m), 7.38-7.48 (2H, m), 8.26 (1H, d, J = 6 Hz). Example 39 Sodium salt of 2- (((4- (2- (2-ethyl-1, 3-dioxolan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 199 (39a) Ethyl 2-ethyl-l, 3-dioxolan-2-yl) Formula 200 A mixture of ethyl 3-oxopentanoate (5 g, 34.7 mmol), ethylene glycol (10.8 g, 174 mmol), triethyl orthoformate (5.14 g, 34.7 mmol), and p-toluenesulfonic acid monohydrate (598 mg, 3.14 mmol) it was stirred at temperature Atmosphere during the night. To the reaction mixture, heptane and ethyl acetate were added to dilute the solution, which was washed with water. The organic layer was washed with a saturated saline solution, dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in heptane and subjected to silica gel column chromatography (solvent elution: n-heptane / ethyl acetate = l / 0-> 10 / l) to obtain the title compound (3.85 g, yield: 58.9%) as a colorless oil. XH NMR (400 MHz, CDC13) d PPM; 0.94 (3H, t, J = 8 Hz), 1.27 (3H, t, J = 7 Hz), 1.83 (2H, q, J = 8 Hz), 2.65 (2H, s), 3.89-4.03 (4H, m ), 4.15 (2H, q, J = 7 Hz). (39b) 2- (2-ethyl-l, 3-dioxolan-2-yl) ethanol Formula 201 To a suspension of tetrahydrofuran (50 ml) of lithium aluminum hydride (800 mg, 21.1 mmol) was added Ethyl (2-ethyl-l, 3-dioxolan-2-yl) acetate (3.85 g, 20.5 mmol) under ice-cooling. The mixture was stirred at room temperature for one hour and 30 minutes and cooled on ice. Next, water (0.8 ml), 15% aqueous sodium hydroxide solution (0.8) was added sequentially ml), and water (2.4 ml) to the mixture under cooling with ice. Magnesium sulfate was added to the mixture and filtered through silica gel. The filtrate was concentrated under reduced pressure to obtain the title compound (2.76 g, 92.1%) as an oil. Xl NMR (400 MHz, CDC13) d PPM; 0.92 (3H, t, J = 8 Hz), 1.68 (2H, q, J = 8 Hz), 1.93 (2H, t, J = 5 Hz), 2.82 (1H, t, J = 5 Hz), 3.76 ( 2H, q, J = 5 Hz), 3.96-4.05 (4H, m). (39c) 2- (((3-Methyl-4- (2- (2-propyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 202 The same procedure as in steps (3c) to (3h) of Example 3 was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and 2- (2-ethyl-l, 3-dioxolan-2-yl) ethanol to obtain the title compound (422 mg, 6 steps: 25%) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.87 (3H, t, J = 8 Hz), 1. 64 (2H, q, J = 8 Hz), 2.07 (2H, t, J = 7 Hz), 2.17 (3H, s), 3.85- 3.94 (4H, m), 4.09 (2H, t, J = 7 Hz ), 4.40 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 6.83-6.90 (2H, m), 6.94 (1H, d, J = 6 Hz), 7. 41-7.49 (2H, m), 8.27 (1H, d, J = 6 Hz). Example 40 Sodium salt of 2- (((4- ((2-ethyl-l, 3-dioxolan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 203 (40a) 2-Oxobutyl Acetate Formula 204 A mixture of l-bromobutan-2-one (10 g, 66.2 mmoles), potassium acetate (7.8 g, 79.4 mmoles), and N, N-dimethylformamide (50 ml) was stirred at room temperature for 5 days. Water was added to the reaction mixture and extracted with diethyl ether twice. The organic layers were combined and washed with a saturated saline solution, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (8.24 g) in the form of a mixture with N, N-dimethylformamide.

X NMR (400 MHz, CDC13) d PPM; 1.10 (3H, t, J = 7 Hz), 2.14 (3H, s), 2.45 (2H, q, J = 7 Hz), 4.66 (2H, s). (40b) (methyl 2-ethyl-l, 3-dioxolan-2-yl) acetate Formula 205 A mixture of 2-oxobutyl acetate (4 g) obtained in step (40a), ethylene glycol (7.82 g, 126 mmol), triethyl orthoformate (3.73 g, 25.2 mmol) and p-toluenesulfonic acid monohydrate (479 mg, 2.52 mmole) was stirred at room temperature overnight. To the reaction mixture was added, water and ethyl acetate, and partitioned. The aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in heptane-ethyl acetate and subjected to silica gel column chromatography (solvent elution: n-heptane / ethyl acetate = 20 / l-> 5 / l) to obtain the title compound ( 1.4 g, 2 step yield: 25%). 1 H NMR (400 MHz, CDC13) d PPM; 0.93 (3H, t, J = 7 Hz), 1.73 (2H, q, J = 7 Hz), 2.09 (3H, s), 3.96-4.03 (4H, m), 4.03 (2H, s). (40c) (2-ethyl-l, 3-dioxolan-2-yl) methanol Formula 206 A mixture of methyl (2-ethyl-l, 3-dioxolan-2-yl) acetate (1.39 g, 7.94 mmol), potassium carbonate (2.19 g, 15.9 mmol), tetrahydrofuran (20 mL) and water (10 mL) ) was stirred at room temperature for 6 hours and 50 minutes. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the residue, which was subjected to filtration in a NH silica gel pad. The filtrate was concentrated under reduced pressure to obtain the title compound (0.75 g, 71.5%) as a colorless oil. Xl NMR (400 MHz, CDC13) d PPM; 0.93 (3H, t, J = 8 Hz), 1. 7K2H, q, J = 8 Hz), 1.95-2.03 (HH, br), 3.53 (2H, d, J = 4 Hz), 3.96-4.06 (4H, m). Sodium salt from (40d) 2 - (((4- ((2-ethyl-l, 3-dioxolan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 207 The same procedure as in steps (3c) to (3h) of Example 3 was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and (2-ethyl-1,3-dioxolan-2-yl) methanol to obtain the title compound (355 mg, 6 steps: 9.6%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.87 (0.3H, t, J = 8 Hz), 1.74 (2H, q, J = 8 Hz), 2.17 (3H, s), 3.87-4.00 (4H, m), 3.96 (2H, s), 4.39 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 6.84-6.91 (2H, m), 6.94 (1H, d, J = 6 Hz), 7.41-7.47 (2H, m), 8.25 (ÍH, d, J = 6 Hz). EXAMPLE 41 Sodium salt of 2- (((4- (2- (2-ethyl-1, 3-dioxolan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -4-methy1 -benzimidazole Formula 208 The same procedure of step (39c) was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and 2- (2-ethyl-1,3-dioxolan-2-yl) ethanol except that 4-methyl-benzimidazole was used -2-thiol obtained in step (54a) of Example 54 in place of 2-mercaptobenzimidazole in step (39c) of Example 39 to obtain the title compound (490 mg, 6 steps: 27%) as a white powder.

X H NMR (400 MHz, DMSO-d 6) d PPM; 0.85 (3H, t, J = 8 Hz), 1.62 (2H, q, J = 8 Hz), 2.05 (2H, t, J = 7 Hz), 2.17 (3H, s), 2.45 (3H, s), 3.83-3.92 (4H, m), 4.07 (2H, t, J = 7 Hz), 4.42 (1H, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.63 (1H, d , J = 7 Hz), 6.73 (1H, t, J = 7 Hz), 6.91 (1H, d, J = 6 Hz), 7.24 (1H, d, J = 8 Hz), 8.25 (ÍH, d, J = 6 Hz). Example 42 Sodium salt of 2- (((4- ((2-ethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-ylmethyl) sulfinyl) -benzimidazole Formula 209 (42a) 2-Oxobutyl benzoate Formula 210 A mixture of l-bromobutan-2-one (7.2 g, 47.7 mmol), sodium benzoate (7.56 g, 52.4 mmol), and N, N-dimethylformamide (72 mL) was stirred at room temperature by 3 hours and 45 minutes. Diethyl ether was added to the reaction mixture and the mixture was washed with water and a saline solution Saturated, dried magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (9.5 g, quantitatively) as a light brown oil. Xl NMR (400 MHz, CDC13) d PPM; 1.13 (3H, t, J = 7 Hz), 2.54 (2H, q, J = 7 Hz), 4.89 (2H, s), 7.43-7.49 (2H, m), 7.57-7.62 (1H, m), 8.08 -8.12 (2H, m). (42b) (2-Ethyl-l, 3-dioxan-2-yl) methyl benzoate Formula 211 A mixture of 2-oxobutyl benzoate (5 g, 26 mmol), 1,3-propanediol (5.94 g, 78 mmol), triethyl orthoformate (3.85 g, 26 mmol) and p-toluenesulfonic acid monohydrate (448 mg, 2.36 g) mmoles) was stirred at room temperature for 3 hours and 30 minutes. To the reaction mixture was added ethyl acetate and diethyl ether and the mixture was washed with water and a saturated saline solution. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in heptane / ethyl acetate (12/1) and subjected to silica gel column chromatography (solvent elution: n-heptane / ethyl acetate = 12 / l) to obtain the title (4.33 g, 65.5%) as a colorless viscous oil. Xl NMR (400 MHz, CDC13) d PPM; 0.98 (3H, t, J = 8 Hz), 1.63-1.87 (2H, m), 1.89 (2H, q, J = 8 Hz), 3.90-4.06 (4H, m), 4.52 (2H, s), 7.42 -7.48 (2H, m), 7.54-7.60 (ÍH, m), 8.06-8.09 (2H, m). (42c) (2-ethyl-l, 3-dioxan-2-yl) methanol Formula 212 A mixture of (2-ethyl-1, 3-dioxan-2-yl) methyl benzoate of (4.33 g, 17.3 mmol), potassium carbonate (4.95 g, 35.9 mmol), tetrahydrofuran (50 mL), and water (20 g) were added. ml) was stirred at room temperature for 11 hours. 5N of aqueous sodium hydroxide solution (2 ml) was added to the mixture, which was stirred at room temperature for 7 hours and then methanol (50 ml) was added thereto, which was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure. Ethyl acetate was added to the residue and the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was dissolved in heptane / ethyl acetate and subjected to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = 2 / l-> 1 / l) to obtain the title compound ( 2.35 g, 92.9%) as a colorless oil.

Xl NMR (400 MHz, CDC13) d PPM; 0.89 (3H, t, J = 8 Hz), 1.52-1.60 (1H, m), 1.83-1.95 (4H, m), 3.58 (2H, d, J = 6 Hz), 3.86-4.0K4H, m). (42d) 2- (((4- ((2-Ethyl-l, 3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 213 The same procedure as in steps (3c) to (3h) of Example 3 was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and (2-ethyl-l, 3-dioxan-2-yl) methanol to obtain the title compound (305 mg, 6 steps: 9.6%) as a solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.83 (3H, t, J = 8 Hz), 1.51-1.71 (2H, m), 1.83 (2H, q, J = 8 Hz), 2.15 (3H, s), 3.79-3.94 (4H, m), 4.15 (2H, s), 4.45 (1H, d, J = 13 Hz), 4.78 (-H, d, J = 13 Hz), 6.93-7.00 (2H, m), 7.04 (1H, d, J = 5 Hz ), 7.45-7.52 (2H, m), 8.26 (1H, d, J = 5 Hz).

Example 43 Sodium salt of 2- (((4- (2- (2- (methoxymethyl) -1, 3-dioxolan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 214 (43a) 2- (2- (methoxymethyl) -1, 3-dioxolan-2-yl) ethanol Formula 215 The same procedure of step (39a) and (39b) of Example 39 was repeated using methyl 4-methoxyacetoacetate to obtain the title compound (5.3 g, 2 steps: 50%) as a colorless oil. Xl NMR (400 MHz, CDC13) d PPM; 2.01 (2H, t, J = 5 Hz), 2.74-2.80 (lH, br), 3.38 (2H, s), 3.42 (3H, s), 3.74-3.80 (2H, br), 4.01-4.06 (4H, m). (43b) Sodium salt of 2- (((4- (2- (2- (methoxymethyl) -1, 3-dioxolan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) - benzimidazole The same procedure as in steps (5d) to (5h) of Example 5 was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and 2- (2- (methoxymethyl) -1,3-dioxolan-2-yl. ) ethanol to obtain the title compound (312 mg, 5 steps 3.9%) as a light yellow foam. 1ti NMR (400 MHz, DMSO-d6) d PPM; 2.10 (2H, t, J = 7 Hz), 2. 15 (3H, s), 3.27 (3H, s), 3.30 (2H, s), 3.86-3.91 (4H, m), 4. 09 (2H, t, J = 7 Hz), 4.38 (1H, d, J = 13 Hz), 4.76 (1H, d, J = 13 Hz), 6.81-6.88 (2H, m), 6.92 (1H, d, J = 6 Hz), 7.40-7.46 (2H, m), 8.26 (1H, d, J = 6 Hz). EXAMPLE 44 Sodium salt of 2- (((4- ((2- (fluoromethyl) -1, 3-dioxan-2-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 217 44a) (2- (hydroxymethyl) -1,3-dioxan-2-benzoate il) methyl Formula 21 To a solution of pyridine (200 ml) of dihydroxyacetone (20 g, 222 mmol), benzoyl chloride (25.8 ml, 222 mmol) was added under cooling with ice, which was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure and ethyl acetate and water were added to dissolve it. The organic layer was absorbed and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with a saturated saline solution, dried magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was suspended in n-heptane / ethyl acetate (1/1) and the insoluble matter was removed by filtration. The filtrate was concentrated and dissolved in ethyl acetate. Silica gel was added to the resulting solution, which was concentrated, and subjected to column chromatography on silica gel (elution solvent: n-heptane / ethyl acetate = 3 / l-> 2 / l-> / l-> 0 / l) to obtain a mixture (16.5 g) containing 3-hydroxy-2-oxopropyl benzoate, as a white solid. A mixture of the mixture (0.5 g) containing 3-hydroxy-2-oxopropyl benzoate, 1,3-propanediol (0.932 ml, 12. 9 mmol), triethyl orthoformate (0.428 ml, 2.58 mmol), and p-toluenesulfonic acid monohydrate (44.5 mg, 0.234 mmol) was stirred at room temperature for 4 days. Another mixture consisting of the mixture (4 g) benzoate containing 3-hydroxy-2-oxopropyl, 1,3-propanediol (7.46 ml, 103 mmol), triethyl orthoformate (3.42 ml, 20.6 mmol), and p-toluenesulfonic acid Monohydrate (356 mg, 1.87 mmol) was stirred at 40 ° C overnight. The two reactions were combined, water and ethyl acetate were added, and the organic layer was absorbed. The organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in n-heptane / ethyl acetate (2/1) and toluene and subjected to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = 3/2) to obtain the compound of the title (4.2 g). X NMR (400 MHz, CDC13) d PPM; 1.58-2.04 (2H, m), 3.72 (2H, s), 3.92-3.99 (2H, m), 4.05-4.13 (2H, m), 4.66 (2H, s), 7.41-7.48 (2H, m), 7.56-7.60 (ÍH, m), 8.02-8.07 (2H, m). (44b) (2- (fluoromethyl) -1,3-dioxan-2-yl) methyl benzoate Formula 219 To a solution of toluene (100 ml) of (2- (hydroxymethyl) -1, 3-dioxan-2-yl) methyl benzoate (4.76 g, 18.8 mmol), 1,8-diazabicyclo [5.4.0] unedec-7-ene (8.43 ml, 56.4 ml) was added mmoles), cooled on ice and added nonafluoro-1-butanesulfonyl chloride (5.06 ml, 28.2 mmol). The mixture was stirred under cooling with ice for 15 minutes, and at 40 ° C for 20 hours, and further it was stirred at room temperature for 8 days. The reaction mixture was extracted by the addition of water and ethyl acetate. The organic layer was washed with a saturated saline solution, dried over magnesium sulfate, and filtered through silica gel, and then, the filtrate was concentrated. The residue was subjected twice to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = 4/1) to obtain the title compound (2.22 g, yield: 46.4%). -? NMR (400 MHz, CDC13) d PPM; 1.63-1.74 (ÍH, m), 1.89-2.01 (ÍH, m), 3.93-4.01 (2H, m), 4.05-4.13 (2H, m), 4.56 (2H, d, J = 47 Hz), 4.66 ( 2H, d, J = 2 Hz), 7.42-7.48 (2H, m), 7.54-7.6K1H, m), 8.03-8.08 (2H, m). (44c) (2- (fluoromethyl) -l, 3-dioxan-2-yl) methanol Formula 220 A mixture of (2- (fluoromethyl) -1, 3- benzoate dioxan-2-yl) methyl (2.22 g, 8.73 mmol), methanol (20 ml) and at IN-aqueous sodium hydroxide solution (13.1 ml) was stirred at room temperature overnight. Ammonium chloride was added to the reaction mixture, which was concentrated. The residue was suspended in tetrahydrofuran and ethyl acetate, and then magnesium sulfate was added and the mixture was stirred for 5 minutes. After performing the NH silica gel filtration, the filtrate was concentrated to obtain the title compound (1.17 g, 89.3%) as a colorless liquid. X NMR (400 MHz, CDC13) d PPM; 1.65-1.75 (ÍH, m), 1. 85-1.96 (1H, m), 3.71 (2H, d, J = 3 Hz), 3.94-4.05 (4H, m), 4.57 (2H, d, J = 47 Hz). Sodium salt from (44d) 2- (((4- ((2- (fluoromethyl) -1, 3-dioxan-2-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula The same procedure as in steps (lc) to (lg) of Example 1 was repeated using 4-chloro-2, 3, 5-trimethylpyridinel-oxide and (2- (fluoromethyl) -1,3-dioxan-2-yl. ) methanol to obtain the title compound (331 mg, 5 steps: 12%) as a yellow solid.

? NMR (400 MHz, DMSO-d6) d PPM; 1.61-1.74 (2H, m), 2.22 (3H, s), 2.25 (3H, s), 3.86-3.95 (4H, m), 3.96 (2H, s), 4.41 (1H, t, J = 13 Hz) , 4.64 (2H, d, J = 47 Hz), 4.75 (1H, d, J = 13 Hz), 6.81-6.88 (2H, m), 7.39-7.46 (2H, m), 8.21 (1H, s). Example 45 Sodium salt of 2- (((4- ((2- (fluoromethyl) -1, 3-dioxolan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 222 (45a) (2- (fluoromethyl) -1,3-dioxolan-2-yl) methanol Formula 223 The same procedure as in steps (44a) to (44c) using dihydroxyacetone except that ethylene glycol was used instead of 1,3-propanediol used in Example 44 to obtain the title compound (543 mg, total yield: 13.8%). XH NMR (400 MHz, CDC13) d PPM; 1.70-1.82 (ÍH, br), 3.66 (2H, d, J = 2 Hz), 4.06 (4H, s), 4.37 (2H, d, J = 47 Hz).

Sodium salt of (45b) 2- (((4- ((2- (fluoromethyl) -1, 3-dioxolan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 2 The same procedure as in steps (3c) a (3h) of Example 3 was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and (2- (fluoromethyl) -1,3-dioxolan-2-yl) methanol to obtain the title compound (140 mg, steps 8.2%) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 2.20 (3H, s), 3.95-4.05 (4H, m), 4.10 (2H, d, J = 2 Hz), 4.38 (1H, d, J = 13 Hz), 4.48 (2H, d, J = 47 Hz ), 4.83 (1H, d, J = 13 Hz), 6.81-6.88 (2H, m), 6.96 (1H, d, J = 6 Hz), 7.39-7.46 (2H, m), 8.27 (1H, d, J = 6 Hz). EXAMPLE 46 Sodium salt of 2- (((4- ((5,5-difluoro-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 225 (46a) 2, 2-difluoropropane-1,3-diyl diacetate Formula 226 A mixture of diacetate 2-oxopropan-1,3-diyl (10.6 g, 60.8 mmol) and diethylaminosulfur trifluoride (24.2 ml, 182 mmol) was stirred at room temperature for 4 days. The reaction mixture was diluted with ethyl acetate, which was cooled on ice, and then a solution of saturated sodium bicarbonate was added and the organic layer was absorbed. The organic layer was washed twice with water, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (10.92 g, 91.6%). 1 H NMR (400 MHz, CDC13) d PPM; 2.13 (6H, s), 4.35 (4H, t, J = 12 Hz). (46b) 2, 2-difluoropropane-1,3-diol Formula 227 A mixture of 2,2-difluoropropan-1,3-diyl diacetate (10.9 g, 55.7 mmol), methanol (300 ml), and a solution of 28% sodium methoxide methanol (32.2 g, 167 mmol) was stirred at At room temperature for 2 hours, DOWEX 50W-X8 (100-200 mesh, form H) was added to the mixture. reaction to adjust the pH to 5. The mixture was filtered and the filtrate was concentrated. To the residue, tetrahydrofuran and ethyl acetate were added to dissolve it. The solution was dried over magnesium sulfate and filtered, and then the filtrate was concentrated. The residue was dissolved in ethyl acetate and filtered through a glass fiber filter paper. The filtrate was concentrated under reduced pressure to obtain the title compound (5.3 g, 84.9%). Xl NMR (400 MHz, CDC13) d PPM; 2.07-2.20 (2H, br), 3.92 (4H, dt, J = 1, 12 Hz). (46c) 2- ((benzyloxy) methyl) -5,5-difluoro-1,3-dioxane Formula 228 A mixture of 2,2-difluoropropan-1,3-diol (1 g, 8.9 mmol), benzyloxyacetaldehyde (1.34 g, 8.9 mmol), p-toluenesulfonic acid monohydrate (154 mg, 0.81 mmol) and toluene (20 ml) are heated under reflux by a condenser equipped with a Dean-Stark apparatus for one hour. The resulting mixture was stirred at room temperature overnight and then the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and silica gel was added thereto. The resulting mixture was concentrated to dryness and subjected to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = 10 / L) to obtain the title compound (930 mg, 42.8%). Xl NMR (400 MHz, CDC13) d PPM; 3.61 (2H, d, J = 5 Hz), 3.75-3.88 (2H, m), 4.13-4.22 (2H, m), 4.61 (2H, s), 4.76 (1H, t, J = 5 Hz), 7.21 -7.40 (5H, m). (46d) (5,5-difluoro-1,3-dioxan-2-yl) methanol Formula 229 A mixture of 2- ((benzyloxy) methyl) -5,5-difluoro-1,3-dioxane (930 mg, 3.81 mmol), 20% palladium hydroxide (353 mg), and ethyl acetate (30 ml) was stirred in a hydrogen atmosphere at room temperature for 4 hours and 25 minutes. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (572 mg, 97.4%) as a colorless oil. XH NMR (400 MHz, CDC13) d PPM; 3.72 (2H, d, J = 5 Hz), 3.78-3.90 (2H, m), 4.16-4.23 (2H, m), 4.69 (1H, t, J = 4 Hz). (46e) Sodium salt of 2- (((4- ((5,5-difluoro-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 230 The same procedure as in steps (lc) < (Ig) of Example 1 was repeated using 4-chloro-2,3-dimethylpyridinel-oxide and (5,5-difluoro-1,3-dioxan-2-yl) methanol to obtain the title compound (375 mg, 5%). steps: 22.7%) as a white powder. H NMR (400 MHz, DMSO-d6) d PPM; 2.19 (3H, s), 4.00-4.25 (6H, m), 4.38 (1H, d, J = 13 Hz), 4.83 (1H, d, J = 13 Hz), 5.17 (1H, t, J = 4 Hz ), 6.81-6.87 (2H, m), 6.96 (1H, d, J = 6 Hz), 7.39-7.45 (2H, m), 8.27 (1H, d, J = 6 Hz). EXAMPLE 47 Sodium salt of 2- (((4- (2- (2,2-dimethyl-l, 3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -5 -methyl-benzimidazole Formula 231 (47a) 5-methyl-benzimidazole-2-thiol Formula 232 First, 3-amino-4-nitrotoluene (6.3 g, 41.4 mmol) and 10% palladium carbon (900 mg) in methanol were suspended. (70 ml) and the mixture was stirred under a hydrogen atmosphere for 3 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration and washed with ethanol. To the reaction mixture was added carbon disulfide (20 ml) and the mixture was stirred at room temperature for 5 days. After the reaction mixture was concentrated, ethyl ether was added to the residue. The generated solid was collected by filtration to obtain the title compound (6.1 g, yield: 89.7%) was obtained as a light yellow solid. H NMR (400 MHz, DMSO-d6) d PPM; 2.33 (3H, s), 6.90-6.93 (2H, m), 7.00 (1H, d, J = 8 Hz). (47b) Sodium salt of 2- (((4- (2- (2,2-dimethyl-1,3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) - 5-methyl-benzimidazole Formula 233 The same procedure as in steps (le) to (lg) of Example 1 was repeated using 5-methyl-benzimidazole-2-thiol (309 mg, 1.88 mmol) obtained in step (47a) and (4- (2- (2,2-dimethyl-1,3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl-methanol (501 mg, 1.88 mmol) to obtain the title compound (118 mg) as a white solid. The solidification operation of the title compound was carried out as follows: Ether was added to the residue and an ultrasonic wave was applied to the resulting mixture The suspension solution obtained was allowed to stand and then the supernatant was removed. The resulting precipitate was subjected to aspiration to dryness to obtain the title compound.1H NMR (400 MHz, DMS0-d6) d PPM, 1.27 (3H, s), 1.33 (3H, s), 1.96-2.04 (2H , m), 2.18 (3H, s), 2.36 (3H, s), 3.59 (1H, t, J = 8 Hz), 4.04-4.14 (3H, m), 4.21-4.26 (ÍH, m), 4.37 ( 1H, dd, J = 4, 13 Hz), 4.80 (1H, dd, J = 2, 13 Hz), 6.69 (1H, d, J = 8 Hz), 6.92 (1H, d, J = 6 Hz), 7.22 (1H, s), 7.31 (1H, d, J = 8 Hz), 8.28 (ÍH, d, J = 6 Hz).

EXAMPLE 48 Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -4-methoxy -benzimidazole Formula 234 (48a) 4-methoxy-benzimidazole-2-thiol Formula 235 A mixture of 2-methoxy-6-nitroaniline (1 g, 5.95 mmol), 10% palladium carbon (300 mg) and methanol (25 ml) was stirred under a hydrogen atmosphere for 4 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration. Carbon disulfide (15 ml) was added to the reaction mixture and the mixture was stirred at room temperature overnight. Triethylamine (1 ml) was added to the reaction mixture, which was stirred at 50 ° C for 3 hours. After the reaction mixture was concentrated, it was addedmethanol (2 ml) and diethyl ether (20 ml) to the residue. The generated solid was collected by filtration to obtain the title compound (950 mg, yield: 88.6%) light orange solid. H NMR (400 MHz, DMSO-d6) d PPM; 3.86 (3H, s), 6. 74 (1H, d, J = 8 Hz), 6.75 (1H, d, J = 8 Hz), 7.05 (1H, t, J = 8 Hz). Sodium salt of (48b) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -4- Methoxy-benzimidazole Formula The same procedure as in steps (le) to (lg) of Example 1 was repeated using 4-methoxy-benzimidazole-2-thiol (260 mg, 1.44 mmol) obtained according to the method of step (48a) and (4) - ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methanol (350 mg, 1.31 mmol) to obtain the title compound (326 mg) as a solid white. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1.36 (3H, t, J = 6 Hz), 2.06-2.14 (ÍH, m), 2.20 (3H, s), 3.75-3.80 (2H, m), 3.88 (3H, s) , 3.97-4.01 (2H, m), 4.10 (2H, d, J = 7 Hz), 4.35 (1H, d, J = 13 Hz), 4.83 (1H, d, J = 13 Hz), 6.33 (1H, d, J = 8 Hz), 6.74 (1H, t, J = 8 Hz), 6.94 (1H, d, J = 6 Hz), 7.05 (1H, d, J = 8 Hz), 8.27 (1H, d, J = 6 Hz). Example 49 Sodium salt of 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -5 - (trifluoromethyl) -benzimidazole Formula 237 (49a) S- (trifluoromethyl) -benzimidazole-2-thiol Formula 238 A mixture of 4-amino-3-nitrobenzotrifluoride (7 g, 34 mmol), 10% palladium carbon (1.3 g) and methanol (70 ml) was stirred under a hydrogen atmosphere for 5 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration. To the reaction mixture was added, carbon disulfide (30 ml) and the mixture was stirred at room temperature overnight, and then the reaction mixture was concentrated. Methanol (60 ml) was added, carbon disulfide (20 ml) and triethylamine (15 ml) were added to the residue and the mixture was stirred at 50 ° C overnight. After the reaction mixture was concentrated, the residue was purified by silica gel column chromatography (silica gel 200 g, eluting solvent: ethyl acetate / heptane = 1 / 3-> 7/3. ethyl / heptane = 7/3, a small amount of methanol was added to the solvent elution) to obtain the title compound (5.3 g, yield: 71.4%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 7.29 (ÍH, d, J = 8 Hz), 7. 35 (1H, s), 7.45 (1H, d, J = 8 Hz), 12.86 (1H, br s). Sodium salt from (49b) 2- (((4- ((5,5-Dimethyl-1,3-dioxan-2-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -5- (trifluoromethyl) ) -benzimidazole Formula 239 The same procedure as in steps (le) to (1 g) of Example 1 was repeated using 5- (trifluoromethyl) -benzimidazole-2-thiol (137 mg, 0.626 mmol) obtained by the method of step (49a) and ( 4- ((5, 5-dimethyl-l, 3-dioxan-2- il) methoxy) -3,5-dimethylpyridin-2-yl) methanol (176 mg, 0.626 mmol) to obtain the title compound (104 mg) as a light yellow solid. Note that when the title compound solidified, heptane (10 ml) and diethyl ether (2 ml) were added and treated ultrasonically. X NMR (400 MHz, DMSO-d6) d PPM; 0.70 (3H, s), 1. 10 (3H, s), 2.20 (3H, s), 2.21 (3H, s), 3.48 (2H, d, J = ll Hz), 3. 57 (2H, d, J = ll Hz), 3.82 (2H, d, J = 4 Hz), 4.76 (1H, t, J = 4 Hz), 7.14 (1H, dd, J = 2, 8 Hz), 7.59 (1H, d, J = 8 Hz), 7.77 (1H, s), 8.21 (ÍH, s). EXAMPLE 50 Sodium salt of 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 240 The same procedure as in the steps (lOd) a (lOf) of Example 10 was repeated using 2-mercaptobenzimidazole (291 mg, 1.94 mmol) and (4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) pyridin-2-yl) methanol (443 mg, 1. 76 mmoles) to obtain the title compound (300 mg) as a white solid. Observe that, in the same procedure that in step (10d), 2-mercaptobenzimidazole was added to the reaction mixture and furthermore 2 equivalents of triethylamine were added. The mixture was stirred at room temperature for 2 days. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 0.30-0.34 (2H, m), 0.56-0.60 (2H, m), 3.24 (2H, d, J = 12 Hz), 3.99 (2H, t, J = 4 Hz), 4.08 (2H, d, J = 12 Hz), 4.94 (1H, t, J = 4 Hz), 6.85-6.88 (3H, m), 6.92 (1H, dd, J = 3, 6 Hz), 7.45 (2H, dd, J = 3, 6 Hz), 8.37 (1H, d, J = 6 Hz). Example 51 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-ethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 241 (51a) 2-Methylpyridin-3-yl trifluoromethanesulfonate Formula 242 First, 3-hydroxy-2-methylpyridine was dissolved (16.2 g, 148 mmol) and N-phenyltrifluoromethanesulfonimide (53.2 g, 149 mmol) in dichloromethane (dehydrated) (450 mL). To the mixture, triethylamine (31 ml, 222 mmol) was added under a nitrogen atmosphere of 1 to 3 ° C. The mixture was stirred for 13 hours and 20 minutes while the temperature was raised to room temperature. The reaction mixture was washed twice with IN of aqueous sodium hydroxide solution, dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (34.3 g, yield: 96.1%) as a brown oil. . H NMR (400 MHz, DMSO-d6) d PPM; 2.54 (3H, s), 7.44-7.52 (1H, m), 7.90-7.96 (ÍH, m), 8.56-8.60 (ÍH, m). (51b) 2-methyl-3- ((trimethylsilyl) ethynyl) pyridine Formula 243 First, 2-methylpyridin-3-yl trifluoromethanesulfonate (34.3 142 mmol), trimethylsilylacetylene (30 ml, 212 mmol), bis (triphenylphosphine) palladium (II) chloride (10.0 g, 14.2 mmol), copper iodide ( I) (2.75 g, 14.4 mmol) in N, N-dimethyl formamide (150 ml). Then, triethylamine (43 ml, 309 mmol) was added under a nitrogen atmosphere room temperature to the mixture. The mixture was then stirred for 3 hours (the exothermic reaction took place). The reaction mixture was separated through ethyl acetate and a saturated aqueous solution of ammonium chloride and the insoluble substance was removed by filtration. The organic layer of the filtrate was washed twice with a saturated aqueous solution of ammonium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to obtain the title compound (22.6 g, yield: 84.1%) as an oil. coffee. X H NMR (400 MHz, DMSO-d 6) d PPM; 0.25 (9H, s), 2.57 (3H, s), 7.22 (1H, dd, J = 5, 8 Hz), 7.79 (1H, dd, J = 2, 8 Hz), 8.43 (1H, dd, J = 2.5 Hz). (51c) 3-ethyl-2-methylpyridine Formula 244 First, 2-methyl-3- ((trimethylsilyl) ethynyl) pyridine (22.6 g, 119 mmol) was dissolved in tetrahydrofuran (dehydrated) (200 ml). To the mixture, tetrabutyl ammonium fluoride (IN tetrahydrofuran solution) (150 mL, 150 mmol) was added. The mixture was stirred at room temperature for one hour. The reaction mixture is divided by ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed twice with a saturated aqueous solution of ammonium chloride, dried over anhydrous magnesium sulfate, and distilled through a rotary evaporator. To the obtained fraction, 10% palladium / carbon (900 mg) was added and stirred under a hydrogen atmosphere at room temperature for 2 hours. The reaction mixture was filtered through anhydrous magnesium sulfate and celite. To the filtrate, 10% palladium / carbon (810 mg) was added and the mixture was stirred under a hydrogen atmosphere at room temperature for 4 hours. The reaction mixture was filtered through anhydrous magnesium sulfate and celite and then the filtrate was concentrated to obtain the title compound (7.25 g, yield: 51.1%) as a colorless oil. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.16 (3H, t, J = 8 Hz), 2.45 (3H, s), 2.60 (2H, q, J = 8 Hz), 7.14 (1H, dd, J = 5, 7 Hz), 7.51 (1H, dd , J = 1, 7 Hz), 8.26 (1H, dd, J = 1, 5 Hz). (51d) 3-ethyl-2-methylpyridine 1-oxide Formula 245 First, 3-ethyl-2-methylpyridine was dissolved (7.25 g, 59.8 mmol) in dichloromethane (dehydrated) (100 ml) and 3-chloroperbenzoic acid (19.0 g, 71.6 mmol, depending on the content was estimated as 65%) was added under a nitrogen atmosphere at an ice-cooling temperature. The mixture was stirred at room temperature for 90 hours. To the reaction mixture was added a saturated aqueous solution of sodium hydrogen carbonate. The aqueous layer was extracted twice with dichloromethane and three times with chloroform. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (silica gel: 100 g, elution solvent: heptane, ethyl acetate / methanol = 10 / l) to obtain the title compound (7.35 g, yield: 89.6%) as a reddish solid. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.14 (3H, t, J = 8 Hz), 2. 35 (3H, s), 2.64 (2H, q, J = 8 Hz), 7.12-7.24 (2H, m), 8.10-8.16 (1H, m). (51e) 3-ethyl-2-methyl-4-nitropyridine 1-oxide Formula 246 During the cooling of a mixture of 1-oxide 3- Ethyl-2-methylpyridine (7.35 g, 53.6 mmol) and sulfuric acid (22.7 g, 231 mmol) in an ice bath, was added dropwise citric acid steaming (3.64 ml, 87.9 mmol), which was stirred at 80 ° C for 8 hours. The reaction mixture was cooled to room temperature and then emptied on ice. The aqueous solution obtained was extracted three times with chloroform. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and concentrated to obtain the title compound (3.37 g, yield: 34.5%) as a yellow solid. X NMR (400 MHz, DMSO-d6) d PPM; 1.21 (3H, t, J = 7 Hz), 2.45 (3H, s), 2.80 (2H, q, J = 7 Hz), 7.88 (1H, d, J = 7 Hz), 8.36 (1H, d, J = 7 Hz). (51f) 4-chloro-3-ethyl-2-methylpyridine 1-oxide Formula 247 First, 3-ethyl-2-methyl-4-nitropyridine 1-oxide (3.37 g, 18.5 mmol) was added to acetyl chloride (20 mL, 281 mmol) in a nitrogen atmosphere at -30 ° C. The mixture was stirred at -30 to 0 ° C for 3 hours. After the reaction mixture was concentrated, the residue was divided by chloroform and a saturated aqueous solution of sodium hydrogen carbonate. After the insoluble substance was removed by filtration, the aqueous layer was extracted twice with chloroform. The organic layers were combined and dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 100 g, eluting solvent: heptane, heptane / ethyl acetate = 50/50) to obtain the title compound (2.10 g, yield: 66.1% ) as a yellow oil. X NMR (400 MHz, DMSO-d6) d PPM; 1.10 (3H, t, J = 8 Hz), 2.42 (3H, s), 2.77 (2H, q, J = 8 Hz), 7.41 (1H, d, J = 7 Hz), 8.16 (1H, d, J = 7 Hz). (51g) 2- (((4- ((2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-ethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 248 The same procedure of step (10b) of Example and the steps (llf) - (lli) of Example 11 were repeated using 1-oxide 4-chloro-3-ethyl-2-methylpyridine, solcetal and 2-mercaptobenzimidazole to obtain the title compound (122 mg, yield: 5.6%) as a white solid. X H NMR (400 MHz, DMS0-d 6) d PPM; 1.07 (3H, t, J = 7 Hz), 1. 30 (3H, s), 1.35 (3H, s), 2.60-2.83 (2H, m), 3.81 (1H, t, J = 7 Hz), 4.01-4.18 (3H, m), 4.32-4.47 (2H, m), 4.67-4.77 (ÍH, m), 6. 79-6.89 (2H, m), 6.95 (1H, d, J = 5H), 7.38-7.49 (2H, m), 8. 29 (1H, d, J = 5 Hz). EXAMPLE 52 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -5-fluoro -benzimidazole Formula 249 (52a) 5-Fluoro-benzimidazole-2-thiol Formula 250 A mixture of 3,4-diamino-1-fluorobenzene (10 g, 79.3 mmole), carbon disulfide (70 ml, 1164 mmole), and methanol (100 ml) was stirred at room temperature for 86 hours and 50 minutes. After the reaction mixture was concentrated, the residue was suspended in hexane. The resulting precipitate was collected by filtration and washed with hexane to obtain the title compound (13.1 g, yield: 98.2%) as a brown solid. X NMR (400 MHz, DMSO-d6) d PPM; 6.90-6.99 (2H, m), 7.06-7.13 (lH, m), 12.58 (1H, s), 12.61 (1H, s). (52b) Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -5- fluoro-benzimidazole Formula 251 The same procedure of step (10b) of Example 10 and step (14b) of Example 14, step (5f) of Example 5, steps (11H NMR) and (lli) of Example 11 were repeated using solketal, 1- 4-chloro-2,3-dimethylpyridine oxide, and 5-fluoro-benzimidazole-2-thiol to obtain the title compound (210 mg, yield: 14.1%) as a white solid. Note that methanol was used as a solvent instead of ethanol in the same operation as step (5f). X H NMR (400 MHz, DMSO-d 6) d PPM; 1.29 (3H, s), 1.30- 1. 40 (3H, m), 2.17 (3H, s), 3.80 (1H, dd, J = 6, 8 Hz), 4.00-4.16 (3H, m), 4.37 (1H, d, J = 13 Hz), 4.42 (1H, quint, J = 6 Hz), 4.70-4.79 (lH, m), 6.62-6.73 (ÍH, m), 6.94 (1H, d, J = 5 Hz), 7.08-7.16 (lH, m), 7.33-7.43 (ÍH, m), 8.27 (1H, d, J = 5 Hz). Example 53 Sodium salt of 2- (((4- (1, 3-dioxan-5-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 252 (53a) 1,3-dioxan-5-ylmethanol Formula 253 A mixture of 2- (hydroxymethyl) -1,3-propanediol (3.06 g, 28.8 mmol), dimethylacetal formaldehyde (9 ml, 102 mmol), lithium bromide (488 mg, 5.62 mmol), p-toluenesulfonic acid monohydrate (491) mg, 2.58 mmol), and dichloromethane (dehydrated) (15 ml) was stirred for 7 days.

After adding triethylamine (1 ml), the reaction mixture was concentrated. The residue was purified by silica gel column chromatography (silica gel: 100 g, eluting solvent: heptane, heptane / ethyl acetate = 1/1, 1/3) to obtain the title compound (1.37 g, yield). : 40.3%) as a colorless oil. X NMR (400 MHz, DMSO-d6) d PPM; 1.76-1.86 (ÍH, m), 3.36 (2H, t, J = 6 Hz), 3.57 (2H, dd, J = 8, 11 Hz), 3.90 (2H, dd, J = 4, 8 Hz), 4.58 (1H, t, J = 6 Hz), 4.63 (1H, d, J = 6 Hz), 4.79 (1H d, J = 6 Hz). (53b) 2- (((4- (1, 3-Dioxan-5-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 254 The same procedure of step (10b) of Example 10 and steps (llf) - (lli) of Example 11 were repeated using 1,3-dioxan-5-ylmethanol, 4-chloro-2,3-dimethylpyridine 1-oxide. , and 2-mercaptobenzimidazole to obtain the title compound (927 mg, yield: 24.2%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 2.15-2.27 (ÍH, m), 2. 19 (3H, s), 3.73-3.85 (2H, m), 3.98-4.06 (2H, m), 4.11 (2H, d, J = 7 Hz), 4.40 (ÍH, d, J = 13 Hz), 4.75 (HH, d, J = 6 Hz), 4.77 (HH, d, J = 13 Hz), 4.83 (HH, d, J = 6 Hz), 6.80-6.91 (2H, m), 6.96 (1H, d, J = 6 Hz), 7.40-7.51 (2H, m), 8.30 (1H, d, J = 6 Hz). EXAMPLE 54 Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -4-methyl -benzimi dazol Formula 255 (54a) 4-methyl-benzimidazole-2-thiol Formula 256 First, 2-methyl-6-nitroaniline (7 g, 46 mmol) and 10% palladium carbon (900 mg) in methanol (70 ml) was suspended and stirred under a hydrogen atmosphere for 5 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration. Carbon disulfide (30 ml) was added to the reaction mixture and the mixture was stirred at room temperature overnight. After solvent was distilled under reduced pressure, ethyl ether was added to the residue. The solid generated was collected by filtration to obtain the title compound (6.9 g, yield: 92.7%) as a light blue solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 2.37 (3H, s), 6.91 (1H, t, J = 8 Hz), 6.94 (1H, d, J = 8 Hz), 7.00 (1H, d, J = 8 Hz). Sodium salt of (54b) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -4- methyl-benzimidazole Formula 257 The same procedure as in steps (llg) - (lli) of Example 11 was repeated using 4-methyl-benzimidazole-2-thiol and (4- ((2,2-dimethyl-l, 3-dioxan-5-yl methoxy) -3-methylpyridin-2-yl) methanol to obtain the title compound (327 mg, yield: 36.5%) as a white solid. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.05-2.14 (HH, m), 2.21 (3H, s), 2.48 (3H, s), 3.75-3.82 (2H, m), 3.97-4.02 ( 2H, m), 4.11 (2H, d, J = 7 Hz), 4.44 (1H, d, J = 13 Hz), 4.77 (1H, d, J = 13 Hz), 6.65 (1H, d, J = 7 Hz), 6.75 (1H, dd, J = 7, 8 Hz), 6.95 (1H, d, J = 6 Hz), 7.26 (1H, d, J = 8 Hz), 8.29 (1H, d, J = 6 Hz).

EXAMPLE 55 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -5-methyl -benzimidazole Formula 258 The same procedure as in steps (llg) - (lli) of Example 11 was repeated using 5-methyl-benzimidazole-2-thiol and (4- ((2,2-dimethyl-l, 3-dioxan-5-yl methoxy) -3-methylpyridin-2-yl) methanol to obtain the title compound (330 mg, yield: 35.6%) as a white solid. XH NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.06-2.15 (HH, m), 2.17 (3H, s), 2.36 (3H, s), 3.75-3.82 (2H, m), 3.97-4.02 ( 2H, m), 4.11 (2H, d, J = 7 Hz), 4.38 (1H, d, J = 13 Hz), 4.77 (1H, d, J = 13 Hz), 6.69 (1H, dd, J = 2 , 8 Hz), 6.95 (1H, d, J = 6 Hz), 7.23 (1H, d, J = 2 Hz), 7.32 (1H, d, J = 8 Hz), 8.29 (1H, d, J = 6 Hz). Example 56 Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -5 -fluoro-benzimidazole Formula 259 The same procedure as in steps (llg) - (lli) of Example 11 was repeated using 5-fluoro-benzimidazole-2-thiol and (4- ((2,2-dimethyl-l, 3-dioxan-5-yl methoxy) -3,5-dimethylpyridin-2-yl) methanol to obtain the title compound (169 mg, yield: 33.7%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1. 36 (3H, s), 2.03-2.13 (ÍH, m), 2.20 (6H, s), 3.76-3.87 (4H, m), 4. 00 (2H, dd, J = 4, 11 Hz), 4.38 (1H, d, J = 13 Hz), 4.74 (1H, d, J = 13 Hz), 6.65-6.74 (ÍH, m), 7.10-7.17 (ÍH, m), 7.36-7.43 (ÍH, m), 8.22 (ÍH, s). Example 57 Sodium salt of 2- (((4- (5,9-dioxaspiro [3.5] non-7-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 260 ; 57a) 1-oxide 4-chloro-2-methylpyridine Formula 261 4-Nitro-2-picoline N-oxide (20 g, 130 mmol) was added to acetyl chloride (120 mL, 1688 mmol) under a nitrogen atmosphere at -25 ° C. The mixture was stirred at -30 to 5 ° C for 4 hours and 15 minutes. After the reaction mixture was diluted with ethyl acetate (approximately 150 ml) and chloroform (approximately 100 ml), the mixture was concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 200 g, eluting solvent: heptane, heptane / ethyl acetate = 75/25, 50/50, 25/75, ethyl acetate, ethyl acetate). ethyl / methanol = 20 / L) to obtain the title compound (3.14 g) as a brown oil. Simultaneously, a crude product was obtained (approximately 17 g). The crude product thus obtained was further purified by silica gel column chromatography (NH silica gel: 300 g, eluting solvent: heptane, heptane / ethyl acetate = 75/25, 40/60, 25/75, ethyl acetate). ethyl) to obtain the title compound (5.39 g) separately as a brown oil. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 2.33 (3H, s), 7. 41 (1H, dd, J = 3, 7 Hz), 7.68 (1H, d, J = 3 Hz), 8.25 (1H, d, J = 7 Hz). (57b) Sodium salt of 2 - (((4- (5,9-dioxaspiro [3.5] non-7-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 262 The same procedure of step (10b) of Example 10 and steps (llf) - (lli) of Example 11 was repeated using 1-oxide of 4-chloro-2-methylpyridine, 5,9-dioxaspiro [3.5] non-7 -methanol obtained with the same method as step (13a), and 2-mercaptobenzimidazole to obtain the title compound (274 mg, yield: 11.4%) as a white solid. Note that in the same operation as in step (llg), after adding 2-mercaptobenzimidazole to the reaction mixture, the mixture was stirred at room temperature for one day and 2 equivalents of triethylamine were added with alcohol base and stirred at 50 ° C for 8 hours and 35 minutes and at room temperature for 84 hours and 40 minutes. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.64 (2H, quint, J = 8 Hz), 1.88-1.97 (ÍH, m), 2.13 (2H, t, J = 8 Hz), 2.15 (2H, t, J = 8 Hz), 3.47-3.62 (3H, m), 3.75-3.85 (3H, m), 4.45 (1H, d, J = 12 Hz), 4.90 (1H, d, J = 12 Hz), 6.58 (1H, d , J = 2 Hz), 6.82 (1H, dd, J = 2, 6 Hz), 6.84-6.91 (2H, m), 7.42-7.48 (2H, m), 8.31 (1H, d, J = 6 Hz) . Example 58 Sodium salt of 2- (((4- (6,10-dioxaspiro [4.5] dec-8-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 263 The same procedure of step (10b) of Example and steps (llf) - (lli) of Example 11 was repeated using 1-oxide of 4-chloro-2-methylpyridine, 6,10-dioxaspiro [4.5] dec-8-ylmethanol obtained with the same step method ( 21a), and 2-mercaptobenzimidazole to obtain the title compound (427 mg, yield: 15.6%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.52-1.63 (4H, m), 1.73-1.86 (4H, m), 1.88-1.98 (ÍH, m), 3.52-3.66 (3H, m), 3.78-3.88 (3H, m), 4.45 (1H, d) , J = 12 Hz), 4.59 (1H, d, J = 12 Hz), 6.60 (1H, d, J = 3 Hz), 6.82 (ÍH, dd, J = 3, 6 Hz), 6.84-6.91 (2H , m), 7.42-7.49 (2H, m), 8.32 (1H, d, J = 6 Hz). EXAMPLE 59 Sodium salt of 2- (((4- ((2,2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 264 The same procedure of step (10b) of Example and steps (llf) - (lli) of Example 11 were repeated using 1-oxide 4-chloro-2-methylpyridine, (2,2-bis (fluoromethyl) -1, 3-dioxan-5-yl) methanol obtained with the same method of step (7a), and 2-mercaptobenzimidazole to obtain the title compound (326 mg, yield: 12.5%) as a white solid. X NMR (400 MHz, DMSO-d6) d PPM; 2.02-2.12 (ÍH, m), 3.68-3.78 (3H, m), 3.90 (1H, dd, J = 7, 10 Hz), 3.97-4.06 (2H, m), 4.40-4.65 (6H, m), 6.66 (1H, d, J = 2 Hz), 6.83-6.92 (3H, m), 7.43-7.50 (2H, m), 8.34 (1H, d, J = 6 Hz). EXAMPLE 60 Sodium salt of 2- (((4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 265 The same procedure of step (10b) of Example 10 and steps (llf) - (lli) of Example 11 was repeated using 1-oxide of 4-chloro-2-methylpyridine, 1,5,9-trioxaspiro [5.5] undec -3-ylmethanol obtained with the same method as step (10a), and 2-mercaptobenzimidazole to obtain the title compound (313 mg, yield: 7.1%) as a white solid. Note that in the same operation as in step (llg), after adding 2-mercaptobenzimidazole to the reaction mixture, the mixture was stirred at room temperature for 86 hours and 30 minutes and 2 more equivalents of triethylamine were added in relation to the alcohol and stirred at 50 ° C for hours and at room temperature for 14 hours and 30 minutes. X NMR (400 MHz, DMSO-d6) d PPM; 1.76 (2H, t, J = 5 Hz), 1.81 (2H, t, J = 5 Hz), 1.91-2.02 (ÍH, m), 3.55 (4H, t, J = 5 Hz), 3.58-3.75 (3H , m), 3.83-3.96 (3H, m), 4.44 (1H, d, J = 12 Hz), 4.58 (1H, d, J = 12 Hz), 6.64 (1H, d, J = 2 Hz), 6.82 -6.91 (3H, m), 7.43-7.49 (2H, m), 8.33 (1H, d, J = 6 Hz).

Example 61 Sodium salt of 2- (((4- (2,3-dihydro-l, 4-benzodioxin-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 266 The same procedure as in steps (8c) to (8g) of Example 8 was repeated using 2-hydroxymethyl-l, 4-benzodioxane to obtain the title compound (141 mg, total yield: 3%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 2.20 (3H, s), 4.19 (1H, dd, J = 7, 12 Hz), 4.30-4.34 (2H, m), 4.38 (1H, dd, J = 5, 13 Hz), 4.46 (1H, dd, J = 2, 12 Hz), 4.61-4.63 (ÍH, m), 4.82 (1H, dd, J = 5, 13 Hz), 6.82-6.93 (6H, m), 6.98 (1H, d, J = 6 Hz ), 7.43 (2H, dd, J = 3, 6 Hz), 8.29 (1H, d, J = 6 Hz). EXAMPLE 62 Sodium salt of 2- (((4- (1,4-dioxan-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 267 (62a) 2-iodometil-l, 4-dioxane Formula 268 To an acetonitrile solution (420 ml) of 2- (allyloxy) ethanol (14 g, 137 mmol), sodium hydrogen carbonate (34.6 g, 410 mmol) and iodine (104 g, 410 mmol) were added and stirred at room temperature. environment for 20 hours. Water was added to the reaction mixture and extracted with ethyl acetate. Next, the organic layer was washed with an aqueous solution of sodium thiosulfate and a saturated saline solution, dried over magnesium sulfate, and filtered through a silica gel column pad, and the filtrate was concentrated to a obtain the title compound (26.5 g, yield 85%) as a yellow liquid. Xl NMR (400 MHz, CDC13) d PPM; 3.10 (2H, d, J = 8 Hz), 3.34 (1H, dd, J = 8, 13 Hz), 3.66-3.98 (6H, m). (62b) 2-hydroxymethyl-l, 4-dioxane Formula 269 To the 2-iodometil-l, 4-dioxane (15 g, 65.8 mmol) obtained in step (62a), potassium acetate (64.6 g, 658 mmol), 18-crown-6 (1.74 g, 6.58 mmol) was added. , and N, N-dimethylformamide (220 ml) and stirred at 80 ° C for 24 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layers were combined and washed with water and a saturated saline solution, dried over magnesium sulfate to obtain an acetoxy compound (5 g). The acetoxy compound was dissolved in methanol (60 ml) and hydrochloric acid (1 ml) was added dropwise. The mixture was stirred at room temperature for one hour and at 40 ° C for one hour, and then neutralized through the addition of triethylamine. The mixture was concentrated and the residue was extracted with ether. The insoluble substance was filtered, and the filtrate was concentrated and the residue was purified by silica gel column chromatography (silica gel: 500 ml, eluting solvent: heptane / ethyl acetate = 3/2, 1/1, 0). / 1) to obtain the title compound (2.15 g, yield: 27%) as a colorless liquid. Xl NMR (400 MHz, CDC13) d PPM; 3.44-3.89 (9H, m). (62c) 1- (1,4-dioxan-2-ylmethoxy) -2-, 3- oxide dimethylpyridine Formula 270 A toluene solution of 2-hydroxymethyl-1,4-dioxane (2.24 g, 19 mmol) obtained in step (62b) and 1-oxide of 4-chloro-2,3-dimethylpyridine (2.5 g, 15.8 mmol) was heated to 140 ° C. KOH (2 g, 34.8 mmol) was added to the solution twice and the resulting mixture was heated under reflux at the same temperature for 3 hours while the water was removed from the reaction system by the use of a Dean-Stark apparatus. NH silica gel was added to the reaction mixture and the solvent was removed. The mixture of the crude reaction product and NH silica gel was subjected to purification by silica gel column chromatography (NH silica gel, eluting solvent: ethyl acetate / methanol = 9 / la 4/1) to obtain the compound of the title (2.9 g, yield: 77%) as a light yellow solid. X NMR (400 MHz, DMSO-d6) d PPM; 2.11 (3H, s), 2.32 (3H, s), 3.37-3.50 (2H, m), 3.58-3.88 (5H, m), 4.01-4.02 (2H, m), 6.93 (1H, d, J = 7 Hz), 8.06.1H, d, J = 7 Hz). (62d) Sodium salt of 2- (((4- (1,4-dioxan-2-ylmethoxy) -3-methylpyridin-2- il) methyl) sulfinyl) -benzimidazole Formula 271 The same procedure as in steps (8d) to (8g) of Example 8 was repeated using 4- (4- (1,4-dioxan-2-ylmethoxy)) -2,3-dimethylpyridine 1-oxide obtained in step (62c) to obtain the title compound (385 mg, total yield: 24%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 2.17 (3H, s), 3.35- 3.51 (2H, m), 3.59-3.90 (5H, m), 4.02 (2H, br s), 4.36 (1H, d, J = 12 Hz), 4.80 (1H, d, J = 12 Hz), 6.83 (2H, dd, J = 4, 6 Hz), 6.91 (1H, d, J = 6 Hz), 7.42 (2H, dd, J = 4, 6 Hz), 8.26 (1H, d, J = 6 Hz). EXAMPLE 63 Sodium salt of 2- (((4- (1,4-dioxan-2-ylmethoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 272 The same procedure as in steps (62a) a (62d) of Example 62 was repeated using 1-oxide 4-chloro-2,3,5-trimethylpyridine to obtain the title compound (355 mg, total yield: 18%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 2.18 (3H, s), 2.2K3H, d, J = 2 Hz), 3.29-3.82 (9H, m), 4.36 (1H, dd, J = 2, 13 Hz), 4.75 (1H, dd, J = 2 , 13 Hz), 6.82 (2H, dd, J = 3, 6 Hz), 7.4K2H, dd, J = 3, 6 Hz), 8.19 (1H, s). EXAMPLE 64 Sodium salt of 2- (((4- (2- (2,2-dimethyl-1,3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 273 The same procedure as in steps (4f) to (4j) of Example 4 (a reprecipitation step was not carried out in the oxidation step with 3-chloroperbenzoic acid) was repeated using 4- (2-hydroxyethyl) -2 , 2-dimethyl-1,3-dioxolan to obtain the title compound (412 mg, total yield: 8.7%) as a light yellow solid. H NMR (400 MHz, DMSO-d6) d PPM; 1.25 (3H, s), 1.3K3H, s), 1.90-2.04 (2H, m), 2.17 (3H, s), 3.57 (1H, t, J = 8 Hz), 3.98-4.26 (4H, m), 4.36 (0.5H, d, J = 13 Hz), 4.37 (0.5H, d, J = 13 Hz), 4.78 (0.5H, d, J = 13 Hz) , 4.78 (0.5H, d, J = 13 Hz), 6.79-6.87 (2H, m), 6.91 (1H, d, J = 6 Hz), 7.37-7.47 (2H, m), 8.26 (1H, d, J = 6 Hz). Example 65 Sodium salt of 2- (((4- ((2, 2-diethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 274 (65a) 4- ((benzyloxy) methyl) -2,2-diethyl-l, 3-dioxolane Formula 275 To a solution of tetrahydrofuran (30 ml) of DL-α-O-benzyl glycerol (3 g, 16.5 mmol), 3-pentanone was added. (17.5 ml, 165 mmol) and p-toluenesulfonic acid monohydrate (300 mg, 1.58 mmol) at room temperature and the mixture was stirred at the same temperature for 22 hours. To the mixture of The reaction was added, a saturated aqueous solution of sodium acid carbonate (5 ml) to adjust the pH to about 8. The generated precipitate was removed by filtration and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (NH silica gel, eluting solvent: heptane / ethyl acetate = 1/3 to 3/1 gradient). A desired fraction was concentrated to obtain the title compound (2.77 g, 67.1% yield) as a colorless oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.75-0.83 (6H, m), 1. 46-1.58 (4H, m), 3.41-3.50 (2H, m), 3.52-3.58 (HH, m), 3.96-4.02 (1H, m), 4.15-4.23 (1H, m), 4.49 (2H, s) ), 7.24-7.36 (5H, m). (65b) (2,2-diethyl-l, 3-dioxolan-4-yl) methanol Formula 276 To a solution of methanol (40 ml) of 4- ((benzyloxy) methyl) -2,2-diethyl-1,3-dioxolane (2.77 g, 11.1 mmol) obtained in step (65a) above, hydroxide was added. palladium (20% by weight Pd (dry basis) on carbon, wet (max water 50%)) (400 mg) and the mixture was stirred under a hydrogen atmosphere at room temperature for 16 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration through celite, and then washed with methanol. The filtrate was concentrated and dried under reduced pressure to obtain the title compound (1593 g, 89.6% yield) as a colorless oil. Xl NMR (400 MHz, CDC13) d PPM; 0.91 (3H, t, J = 7 Hz), 0. 93 (3H, t, J = 7 Hz), 1.60-1.72 (4H, m), 1.86 (1H, t, J = 6 Hz), 3.55-3.64 (ÍH, m), 3.67-3.84 (2H, m) , 4.01-4.08 (ÍH, m), 4.20-4.28 (ÍH, m). (65c) Sodium salt of 2- (((4- ((2,2-diethyl-l, 3-dioxolan-4-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 277 The same procedure as in steps (4f) to (4j) of Example 4 (no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using (2, 2-diethyl-1, 3- dioxolan-4-yl) methanol obtained in step (65b) above to obtain the title compound (418 mg, total 14.3% yield) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.78-0.88 (6H, m), 1.51-1.66 (4H, m), 2.18 (1.5H, s), 2.18 (1.5H, s), 3.76 (1H, t, J = 8 Hz), 4.02-4.20 (3H, m), 4.32-4.48 (2H, m), 4.76 (0.5H, d, J = 13 Hz), 4.78 (0.5H, d, J = 13 Hz), 6.78-6.88 (2H, m), 6.94 (1H, d, J = 6 Hz), 7.37-7.47 (2H, m), 8.26 (1H, d, J = 6 Hz). EXAMPLE 66 Sodium salt of 2- (((4- (1,3-dioxolan-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 278 (66a) 2- ((benzyloxy) methyl) -1, 3-dioxolane Formula 279 A mixture of benzyloxyacetaldehyde (3 g, 20 mmol), ethylene glycol (1.23 ml, 22 mmol), p-toluenesulfonic acid monohydrate (344 mg, 1.8 mmol), and toluene (15 ml) was stirred at 140 ° C for 2 hours and further it was stirred at 150 ° C for 3 hours. After cooling on ice, a 2N aqueous solution of sodium hydroxide and ethyl acetate was added to the reaction mixture. An organic layer was separated, washed with water (three times) and a saturated saline solution.

The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (NH silica gel, elution solvent: heptane / ethyl acetate = 1/9 to 9/1 gradient). The desired fractions were concentrated to obtain the title compound (3.01 g, 77.5% yield) as a light yellow oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 3.45 (2H, d, J = 4 Hz), 3.74-3.92 (4H, m), 4.51 (2H, s), 4.98 (1H, t, J = 4 Hz), 7.24-7.38 (5H, m). (66b) 1,3-dioxolan-2-ylmethanol Formula 280 To a solution of methanol (100 ml) of 2- ((benzyloxy) methyl) -1,3-dioxolane (3.01 g, 15.5 mmol) obtained in step (66a) above, palladium hydroxide (20% by weight) was added. Pd (dry base) on carbon, wet (max 50% water)) (300 mg) and the mixture was stirred under a hydrogen atmosphere at room temperature for 15 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration through celite, and then washed with methanol. The filtrate was concentrated and dried under reduced pressure to obtain the title (1.57 g, 97.3% yield) as a light yellow oil. Xl NMR (400 MHz, CDC13) d PPM; 1.89 (1H, br s), 3.66-3.72 (2H, m), 3.88-4.08 (4H, m), 5.01 (1H, t, J = 3 Hz). (66c) 2- (((4- (1, 3-dioxolan-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 281 The same procedure as in steps (4f) to (4j) described in Example (no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using 1,3-dioxolan-2-ylmethanol obtained in step (66b) above to obtain the title compound (411 mg, total 17.2% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 2.17 (3H, s), 3.80- 4.00 (4H, m), 4.07 (2H, d, J = 4 Hz), 4.39 (1H, d, J = 13 Hz), 4.79 (1H, d, J = 13 Hz ), 5.24 (1H, t, J = 4 Hz), 6.80-6.89 (2H, m), 6.94 (1H, d, J = 6 Hz), 7.38-7.46 (2H, m), 8.26 (1H, d, J = 6 Hz).

EXAMPLE 67 2- (((3-Methyl-4- ((2-methyl-1, 3-dioxolan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 282 (67a) 2- ((benzyloxy) methyl) -2-methyl-l, 3-dioxolane Formula 283 A mixture of l-benzyloxy-2-propanone (4.94 g, 30.1 mmol), ethylene glycol (20 ml, 359 mmol), triethyl orthoformate (5 ml, 30.1 mmol), and p-toluenesulfonic acid monohydrate (130 mg, 0.683) mmoles) was stirred at room temperature for 61.5 hours. A saturated aqueous sodium hydrogen carbonate solution (20 ml) was added to the reaction mixture and the mixture was extracted twice with chloroform (50 ml) and the organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (NH silica gel, eluting solvent: heptane / ethyl acetate = 1/0 to 4/1. gradient). The desired fractions were concentrated to obtain the title compound (5.67 g, 90.5% yield) as a colorless oil. X NMR (400 MHz, DMSO-d6) d PPM; 1.26 (3H, s), 3.34 (2H, s), 3.85 (4H, s), 4.51 (2H, s), 7.22-7.38 (5H, m). (67b) (2-methyl-l, 3-dioxolan-2-yl) methanol Formula 284 HO or / -n 9 xJ To a solution of methanol (100 ml) of 2- ((benzyloxy) methyl) -2-methyl-1,3-dioxolane (5.66 g, 27.2 mmol) obtained in step (67a) above, palladium hydroxide was added ( 20% by weight Pd (dry bases) on carbon, wet (max water 50%)) (500 mg) and the mixture was stirred under a hydrogen atmosphere at room temperature for 17 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration through celite, and then washed with methanol. The filtrate was concentrated and dried under reduced pressure to obtain the title compound (2.96 g, 92.1% yield) as a light green oil. Xl NMR (400 MHz, CDC13) d PPM; 1.35 (3H, s), 1.82-1.90 (1H, br), 3.54 (2H, d, J = 6 Hz), 4.01 (4H, s). (67c) Sodium salt of 2- (((3-methyl-4- ((2-methyl-1, 3- dioxolan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) benzimidazole Formula 285 The same procedure as in steps (4f) to (4j) of Example 4 (no reprecipitation step was carried out in the oxidation step with 3-chloroperbenzoic acid) was repeated using (2-methyl-1,3-dioxolan- 2-yl) methanol obtained in step (67b) above to obtain the title compound (263 mg, total 12.9% yield) as a light yellow solid. 1 H NMR (400 MHz, DMS0-d 6) d PPM; 1.39 (3H, s), 2. 19 (3H, s), 3.88-4.00 (4H, m), 3.96 (2H, s), 4.37 (1H, d, J = 13 Hz), 4.79 (1H, d, J = 13 Hz), 6.78-6.88 (2H, m), 6.92 (1H, d, J = 6 Hz), 7.37-7.46 (2H, m), 8.25 (1H, d, J = 6 Hz). Example 68 Sodium salt of 2 - ((((4 - ((2S) -1,4-dioxaspiro [4.5] dec-2-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 286 The same procedure as in steps (4f) to (4j) of Example 4 (no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using (+) -1,4-dioxaspiro [4.5 ] decane-2-methanol to obtain the title compound (500 mg, total 16.8% yield) as a white solid. XR NMR (400 MHz, DMSO-d6) d PPM; 1.24-1.63 (10H, m), 2.18 (3H, s), 3.76-3.84 (HH, m), 4.01-4.14 (3H, m), 4.37 (0.5H, d, J = 13 Hz), 4.38 (0.5 H, d, J = 13 Hz), 4.38-4.46 (HH, m), 4.77 (0.5H, d, J = 13 Hz), 4.78 (0.5H, d, J = 13 Hz), 6.79-6.87 (2H , m), 6.94 (1H, d, J = 6 Hz), 7.37-7.46 (2H, m), 8.26 (1H, d, J = 6 Hz). Example 69 Sodium salt of 2- (((3-methyl-4- (2- (2-methyl-1,3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 287 (69a) 2- (2- (benzyloxy) ethyl) -2-methyl-l, 3-dioxolane Formula 288 A mixture of 4-benzyloxy-2-butanone (10 g, 56.1 mmol), ethylene glycol (40 ml, 718 mmol), triethyl orthoformate (9.3 ml, 55.9 mmol) and p-toluenesulfonic acid monohydrate (290 mg, 1.52 mmol) ) was stirred at room temperature for 13.5 hours. A saturated aqueous sodium hydrogen carbonate solution (40 ml) was added to the reaction mixture and the mixture was extracted three times with chloroform (50 ml).

The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (NH silica gel, eluting solvent: heptane / ethyl acetate = 1/4 to 4/1 gradient). The desired fractions were concentrated to obtain the title compound (10.08 g, 80.8% yield) as a colorless oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.23 (3H, s), 1.86 (2H, t, J = 7 Hz), 3.48 (2H, t, J = 7 Hz), 3.75-3.86 (4H, m), 4.42 (2H, s), 7.22-7.36 (5H, m). (69b) 2- (2-methyl-l, 3-dioxolan-2-yl) ethanol Formula 289 To a methanol solution (150 ml) of 2- (2- (benzyloxy) ethyl) -2-methyl-1,3-dioxolane (10.1 g, 45.4 mmol) obtained in step (69a), palladium hydroxide was added ( 20% by weight Pd (dry bases) on carbon, wet (max water 50%)) (900 mg) and the mixture was stirred under a hydrogen atmosphere at room temperature for 16 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration through celite, and then washed with methanol. The filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (silica gel, solvent elution: heptane / ethyl acetate = l / 0-> l / l-> 0 / l gradient). The desired fractions were concentrated to obtain the title compound (3.5 g, 58.3% yield) as a light yellow oil.

X NMR (400 MHz, DMSO-d6) d PPM; 1.21 (3H, s), 1.73 (2H, t, J = 7 Hz), 3.40-3.50 (2H, m), 3.75-3.86 (4H, m), 4.30 (H, t, J = 5 Hz). (69c) 2- (((3-Methyl-4- (2- (2-methyl-1, 3-dioxolan-2-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula The same procedure as in steps (4f) to (4j) of Example 4 (no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using 2- (2-methyl-1, 3- dioxolan-2-yl) ethanol obtained in step (69b) to obtain the title compound (410 mg, total 14.4% yield) as a light yellow solid. X NMR (400 MHz, DMSO-d6) d PPM; 1.31 (3H, s), 2.08 (2H, t, J = 7 Hz), 2.15 (3H, s), 3.87 (4H, s), 4.10 (2H, t, J = 7 Hz), 4.38 (1H, d) , J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.77-6.89 (2H, m), 6.92 (1H, d, J = 6 Hz), 7.35-7.49 (2H, m), 8.26 (1H, d, J = 6 Hz).

EXAMPLE 70 Sodium salt of an optical isomer of 2- (((3-methyl-4- ((2-methyl-1, 3-dioxolan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) - Benzimidazole Formula 291 It was dissolved in water. 2- (((3-Methyl-4- ((2-methyl-1, 3-dioxolan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt ( racemate) (185 mg) obtained in the same manner as in steps (67a) to (67c). To the solution, dichloromethane and a saturated aqueous solution of ammonium chloride were added. The aqueous layer was further extracted with dichloromethane. The organic layers were combined and dried over anhydrous sodium sulfate and concentrated. To the resulting free form, a small amount of diethylamine was added and the mixture was separated through HPLC (column: CHIRALCEL OD-H 2 cmfx25 cm (manufactured by Daicel Chemical Industries, Ltd.), mobile phase: hexane / ethanol / diethylamine = 80/20 / 0.1 (v / v / v), flow rate: 9 ml / min, detection: 254 nm). On the other hand, an aqueous solution of sodium hydroxide (100 μl) was placed in each of the test tubes, in advance. A fraction of an optical isomer having a short retention time, and a fraction of an optical isomer having a long retention time were concentrated separately and the residue was dissolved separately in water. To each of the solutions, dichloromethane and a saturated aqueous solution of ammonium chloride were added. The aqueous layers were further extracted separately with dichloromethane. The organic layers were combined separately and dried over anhydrous sodium sulfate and concentrated. In the above-mentioned manner, a free form (59 mg) of the optical isomer having a short retention time and a free form (56 mg) of the optical isomer having a long retention time each as a light gray foam. Each of the free forms of the optical isomer was subjected to the same operation to obtain sodium salt from how it was carried out in step (4j) (sodium salt formation) to obtain a sodium salt of (58 mg) of the optical isomer having a short retention time and a sodium salt of (53 mg) of the optical isomer having a long retention time each as a light yellow solid. X NMR (400 MHz, DMSO-d6) d PPM; The graphs of both isomers are the same as those of the sodium salt of 2- (((3-methyl-4- ((2-methyl-l, 3-dioxolan-2-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole (racemate).

HPLC; (Conditions) column: CHIRALCEL OD-H (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm), eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.6 ml / min, detection : UV 254 nm). (Results of analysis) The retention time of a Sodium salt of the optical isomer having a short retention time: 16 minutes, enantiomeric excess: 100% ee; and the retention time of a Sodium salt of the optical isomer having a long retention time: 22 minutes, enantiomeric excess: 100% ee. EXAMPLE 71 Sodium salt of 2- (((4- (2- ((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 292 (71a) 2- ((4R) -2, 2-dimethyl-l, 3-dioxolan-4-yl) ethanol Formula 293 A mixture of (R) - (+) -1,2,4-butanetriol (30g, 283mmol), acetone (200ml, 2724mmol) and p-toluenesulfonic acid monohydrate (1.4g, 7.36mmol) was stirred at room temperature for 16.5 hours. Triethylamine was added to the reaction mixture and the mixture was concentrated. The crude product was purified by silica gel column chromatography (silica gel, elution solvent: heptane / ethyl acetate = l / 0-> l / l-> l / 3 gradient). The desired fractions were concentrated to obtain the title compound (29.9 g, 72.3% yield) as a colorless oil. Xl NMR (400 MHz, CDC13) d PPM; 1.37 (3H, s), 1.43 (3H, s), 1.78-1.95 (3H, m), 3.60 (1H, t, J = 8 Hz), 3.76-3.85 (2H, m), 4.09 (1H, dd, J = 6, 8 Hz), 4.27 (1H, quint, J = 6 Hz). (71b) 2 - (((4- (2- ((4R) -2,2-dimethyl-l, 3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl salt sulfinyl) -benzimidazole Formula 294 The same procedure as in steps (4f) to (4j) of Example 4 (recrystallization was performed through the use of heptane in the step to obtain picolyl alcohol, and no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using 2- ((4R) -2,2-dimethyl-1,3-dioxolan-4-yl) ethanol obtained in step (71a) to obtain the title compound (320 mg, total 8.5% yield) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.26 (3H, s), 1. 32 (3H, s), 1.91-2.04 (2H, m), 2.17 (3H, s), 3.57 (1H, t, J = 7 Hz), 3.98-4.28 (4H, m), 4.36 (0.5H, d , J = 13 Hz), 4.37 (0.5H, d, J = 13 Hz), 4.80 (0.5H, d, J = 13 Hz), 4.80 (0.5H, d, J = 13 Hz), 6.78-6.87 ( 2H, m), 6.91 (1H, d, J = 6 Hz), 7.36-7.46 (2H, m), 8.25 (1H, d, J = 6 Hz). Example 72 Sodium salt of 2- (((4- (2- ((4S) -2, 2-dimethyl-l, 3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 295 (72a) 2- ((4S) -2, 2-dimethyl-l, 3-dioxolan-4-yl) ethanol Formula 296 A (S) - (-) - 1,2,4-butanetriol (30 g, 283 mmol), acetone (200 ml) and p-toluenesulfonic acid monohydrate (1.4 g, 7.36 mmol) were added and the mixture was stirred at Room temperature during the night. Triethylamine (4 ml) was added to the reaction mixture and the mixture was concentrated. The residue was purified by silica gel column chromatography (silica gel 350 g, eluting solvent: ethyl acetate / heptane = 18 / 82-> 6/4) to obtain the title compound (30.2 g, yield: 73%) as a colorless oil. Xl NMR (400 MHz, CDC13) d PPM; 1.37 (3H, s), 1.43 (3H, s), 1.83 (2H, q, J = 6 Hz), 2.20 (1H, t, J = 6 Hz), 3.60 (1H, t, J = 8 Hz), 3.80 (2H, q, J = 6 Hz), 4.09 (1H, dd, J = 6, 8 Hz), 4.27 (1H, quint, J = 6 Hz). Sodium salt of (72b) 2- (((4- (2- ((4S) -2,2-dimethyl-1,3-dioxolan-4-yl) ethoxy) -3-methylpyridin-2-yl) methyl sulfinyl) -benzimidazole Formula 297 The same procedure as in steps (4f) to (4j) of Example 4 (recrystallization was performed through the use of heptane in the step to obtain picolyl alcohol, and no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using 2- ((4S) -2,2-dimethyl-1,3-dioxolan-4-yl) ethanol obtained in step (72a) above to obtain the title compound (386 mg, total 10.1% yield) as a light yellow solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.25 (3H, s), 1.31 (3H, s), 1.90-2.05 (2H, m), 2.17 (3H, s), 3.57 (1H, t, J = 8 Hz), 4.00-4.27 (4H, m) , 4.37 (0.5H, d, J = 13 Hz), 4.37 (0.5H, d, J = 13 Hz), 4.78 (0.5H, d, J = 13 Hz), 4.78 (0.5H, d, J = 13 Hz), 6.79-6.87 (2H, m), 6.91 (1H, d, J = 6 Hz), 7.38-7.46 (2H, m), 8.26 (1H, d, J = 6 Hz).

Example 73 Sodium salt of 2- (((3-Methyl-4- (2- (8-methyl-1,4,7,9-tetraoxaspiro [4.5] decyl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 298 (73a) (8-methyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8-yl) methyl acetate Formula 299 A mixture of 1,3-dioxolane-2,2-diyldimethanol (4 g, 29.8 mmol) separately obtained in the same manner as in step s (4a) to (4c), methyl acetoacetate (4.9 ml, 45.4 mmol) , triethyl orthoformate (5.2 ml, 31.3 mmole), and p-toluenesulfonic acid monohydrate (163 mg, 0.856 mmole) was stirred at room temperature for 3 hours. To the mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate was added. The organic layer was washed twice with water and with a saline solution, and dried over sulphate sodium anhydrous and concentrated. The crude product was purified by silica gel column chromatography (silica gel, elution solvent: heptane / ethyl acetate = l / 0-3 / l-l / l gradient). A desired fraction was concentrated to obtain the title compound (3.46 g, 50.0% yield) as a colorless oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.41 (3H, s), 2.75 (2H, s), 3.57 (3H, s), 3.60 (2H, d, J = 12 Hz), 3.65 (2H, d, J = 12 Hz), 3.84 (4H, s ). (73b) 2- (8-methyl-l, 4,7, 9-tetraoxaspiro [4.5] dec-8-yl) ethanol Formula 300 To a THF solution (40 ml) of methyl (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) acetate (3.46 g, 14.9 mmol) obtained in step (73a) , lithium aluminum hydride (679 mg, 17.9 mmol) was added at 0 ° C and the mixture was stirred at 0 ° C at room temperature for 3 hours. After the reaction was terminated by the sequential addition of water (0.68 ml), 2N of aqueous sodium hydroxide solution (0.68 ml), and water (2 ml), sodium sulfate were added thereto. anhydrous and celite. The mixture was filtered through a glass filter. The precipitate was washed with ethyl acetate and concentrated to obtain the title compound (2.96 g, 97.3% yield) as a colorless oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.27 (3H, s), 1. 81 (2H, t, J = 7 Hz), 3.44 (2H, dt, J = 6, 7 Hz), 3.55 (2H, d, J = 12 Hz), 3.60 (2H, d, J = 12 Hz), 3.72-3.89 (4H, m), 4.31 (1H, t, J = 6 Hz). (73c) 2- (((3-Methyl-4- (2- (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) pyridin-2- sodium salt il) methyl) sulfinyl) -benzimidazole Formula 301 The same procedure as in steps (4f) to (4j) of Example 4 was repeated using 2- (8-methyl-1, 7, 9-tetraoxaspiro [4.5] dec-8-yl) ethanol obtained in step ( 73b) above to obtain the title compound (298 mg, total . 1% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.38 (3H, s), 2.11- 2.20 (5H, m), 3.62 (2H, d, J = 12 Hz), 3.66 (2H, d, J = 12 Hz), 3. 79-3.90 (4H, m), 4.11 (2H, t, J = 7 Hz), 4.37 (1H, d, J = 13 Hz), 4.77 (1H, d, J = 13 Hz), 6.80-6.87 (2H , m), 6.90 (1H, d, J = 6 Hz), 7. 38-7.45 (2H, m), 8.26 (1H, d, J = 6 Hz). Example 74 Sodium salt of 5-methyl-2- (((3-methyl-4- (2- (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) pyridin -2-ylmethyl) sulfinyl) -benzimidazole Formula 302 The same procedure as in steps (4f) to (4j) of Example 4 was repeated using 2- (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethanol obtained in step (73b) above and 5-methyl-benzimidazole-2-thiol obtained in step (47a) to obtain the title compound (188 mg, total 12.4% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.38 (3H, s), 2.09-2.20 (5H, m), 2.34 (3H, s), 3.62 (2H, d, J = 12 Hz), 3.66 (2H, d, J = 12 Hz), 3.77-3.92 (4H, m), 4.10 (2H, t, J = 6 Hz), 4.35 (1H, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.67 (1H, d, J = 8 Hz), 6.89 (1H, d, J = 6 Hz), 7.20 (1H, s), 7.29 (1H, d, J = 8 Hz), 8.25 (1H, d, J = 6 Hz).

EXAMPLE 75 Sodium salt of 2- (((4- (2- (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) pyridin-2-yl) methyl) sulfinil ) -benzimidazole Formula 303 The same procedure as in steps (5d) to (5h) of Example 5 (a reprecipitation step was not performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using 2- (8-methyl-1,4, 7, 9-tetraoxaspiro [4.5] dec-8-yl) ethanol obtained in step (73b) above and 4-chloro-2-methylpyridine 1-oxide obtained in step (57a) to obtain the title compound (860 mg, total 20.2% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.31 (3H, s), 2.05 (2H, t, J = 7 Hz), 3.59 (2H, d, J = 12 Hz), 3.64 (2H, d, J = 12 Hz), 3.78-4.03 (6H, m ), 4.45 (1H, d, J = 12 Hz), 4.54 (1H, d, J = 12 Hz), 6.71-6.90 (4H, m), 7.37-7.48 (2H, m), 8.32 (1H, d, J = 6 Hz).

Example 76 Sodium salt of 2- (((4- (2- (9-methyl-1, 5, 8, 10-tetraoxaspiro [5.5] undec-9-yl) ethoxy) pyridin-2-yl) methyl) sulfinil ) -benzimidazole Formula 304 (76a) 2, 2-bis ((benzyloxy) methyl) -1,3-dioxane Formula 305 A mixture of 1,3-bis (benzyloxy) acetone (20 g, 73.9 mmol) obtained in the same manner as in step (4a) above, 1,3-propanediol (54 ml, 747 mmol), triethyl orthoformate ( 13 ml, 78.2 mmol), and p-toluenesulfonic acid monohydrate (394 mg, 2.07 mmol) was stirred at 50 ° C for 14.5 hours. To the mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate was added. The organic layer was washed with water and a saline solution, dried over anhydrous sodium sulfate, and concentrated. The obtained crude product was purified by gel column chromatography of silica (silica gel, solvent elution: heptane / ethyl acetate = l / 0-3 / l gradient). The desired fractions were concentrated to obtain the title compound (17.46 g, 71.9% yield) as a light yellow oil. [1008] Xl NMR (400 MHz, DMSO-d6) d PPM; 1.60 (2H, quint, J = 6 Hz), 3.60 (4H, s), 3.82 (4H, t, J = 6 Hz), 4.49 (4H, s), 7.22-7.35 (10H, m). (76b) 1,3-dioxane-2,2-diyldimethanol Formula 306 To a solution of ethyl acetate (200 ml) of 2,2-bis ((benzyloxy) methyl) -1,3-dioxane (17.46 g, 53.2 mmole) obtained in step (76a) above, palladium hydroxide was added. (20% by weight Pd (dry bases) on carbon, wet (max water 50%)) (1.7 g) and the mixture was stirred under a hydrogen atmosphere at room temperature for 46 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration, and then the washing was carried out with ethyl acetate. The filtrate was concentrated to obtain the title compound (7.67 g, 97.3% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.58 (2H, quint, J = 6 Hz), 3.47 (4H, d, J = 6 Hz), 3.80 (4H, t, J = 6 Hz), 4.43 (2H, t, J = 6 Hz). (76c) 9-methyl-l, 5,8,10-tetraoxaspiro [5.5] undec-9-yl) methyl acetate Formula 307 A mixture of 1,3-dioxane-2,2-diyldimethanol (4 g, 27 mmol) obtained in step (76b) above, methyl acetoacetate (4.4 ml, 40.8 mmol), triethyl orthoformate (4.6 ml, 27.7 mmol) ), and p-toluenesulfonic acid monohydrate (160 mg, 0.843 mmol) was stirred at room temperature for 4.5 hours. To the mixture, a saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate was added. The organic layer was washed twice with water and a saline solution, dried over anhydrous sodium sulfate and concentrated. The crude product obtained was purified by silica gel column chromatography (silica gel, elution solvent: heptane / ethyl acetate = 1 / 0-4 / 1 / l gradient). The desired fractions were concentrated to obtain the title compound (1.60 g, 24.1% yield) as a colorless oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.39 (3H, s), 1.53-1.63 (2H, m), 2.72 (2H, s), 3.56 (3H, s), 3.70-3.86 (8H, m). (76d) 2- (9-methyl-l, 5, 8, 10-tetraoxaspiro [5.5] undec- 9-il) ethanol Formula 308 To a THF solution (20 ml) of methyl (9-methyl-1, 5, 8, 10-tetraoxaspiro [5.5] undec-9-yl) acetate (1.6 g, 6.5 mmol) obtained in step (76c) , lithium aluminum hydride (300 mg, 7.9 mmol) was added at 0 ° C and the mixture was stirred at 0 ° C at room temperature for one hour. After the reaction was terminated by the sequential addition of water (0.3 ml), 2N of aqueous sodium hydroxide solution (0.3 ml), and water (0.9 ml), anhydrous sodium sulfate and celite were added thereto. The mixture was filtered through a glass filter. The precipitate was washed with ethyl acetate and concentrated. The resulting residue was purified by silica gel column chromatography (silica gel, elution solvent: heptane / ethyl acetate = 3 / l-l / 4 gradient). The desired fractions were concentrated to obtain the title compound (950 mg, 67.0% yield) as a colorless oil. Xl NMR (400 MHz, DMSO-dg) d PPM; 1.24 (3 Hz s), 1.53-1.63 (2H, m), 1.78 (2H, t, J = 7 Hz), 3.43 (2H, dt, J = 6, 7 Hz), 3.67-3.85 (8H, m) , 4.30 (1H, t, J = 6 Hz). (76e) Sodium salt of 2- (((4- (2- (9-methyl-1, 5, 8, 10-tetraoxaspiro [5.5] undec-9-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 309 The same procedure as in steps (5d) to (5h) of Example 5 (no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using 2- (9- methyl-l, 5,8,10-tetraoxaspiro [5.5] undec-9-yl) ethanol obtained in step (76d) above to obtain the title compound (228 mg, total 11.4% yield) as a white solid. Xl NMR (400 MHz, DMS0-d6) d PPM; 1.28 (3H, s), 1.53-1.64 (2H, m), 2.02 (2H, t, J = 7 Hz), 3.68-4.00 (10H, m), 4.46 (1H, d, J = 12 Hz), 4.54 (1H, d, J = 12 Hz), 6.72-6.90 (4H, m), 7.36-7.47 (2H, m), 8.32 (1H, d, J = 6 Hz). Example 77 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -6,7-dihydro-lH- [ 1.4] ioxino [2,3-f] benzimidazole Formula 310 Na The same procedure as in steps (5f) to (5h) previous (a reprecipitation step was not performed in the oxidation step with 3-chloroperbenzoic acid) was repeated using (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin -2-yl) methanol obtained in step (12b) and 6,7-dihydro-lH- [1.4] dioxino [2 '.3': 4.5] benzo [d] imidazole-2-thiol to obtain the title compound (137 mg, total 25.8% yield) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.32 (3H, s), 1. 35 (3H, s), 2.03-2.14 (HH, m), 2.16 (3H, s), 3.70-3.82 (2H, m), 3.92-4.02 (2H, m), 4.09 (2H, d, J = 7 Hz), 4.14 (4H, s), 4.32 (1H, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.83 (2H, s), 6.92 (1H, d, J = 6 Hz), 8.26 (1H, d, J = 6 Hz). EXAMPLE 78 Sodium salt of 6 - (((4 - ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -5H- [ 1.3] dioxolo [4,5-f] benzimidazole Formula 311 (78a) 5, 6-dinitro-l, 3-benzodioxol Formula 312 A mixture of 5-nitro-l, 3-benzodioxol (10 g, 59.8 mmol), tetramethylammonium nitrate (10.6 g, 77.7 mmol) and dichloromethane (100 ml) was stirred under ice-cooling and then trifluoromethanesulfonic anhydride was added dropwise. (13.1 ml, 77.7 mmoles) thereto below 7 ° C The mixture was stirred at room temperature for 30 minutes and heated under reflux overnight. The reaction mixture was stirred under ice cooling and tetramethylammonium nitrate (4.07 g, 29.9 mmol) and trifluoromethanesulfonic anhydride (5.03 mL, 29.9 mmol) was added thereto. The resulting mixture was stirred at 50 ° C for 6 hours. The reaction mixture was cooled to room temperature and a saturated aqueous solution of sodium acid carbonate and ice was added. The mixture was stirred and the organic layer was removed. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over sodium sulfate, magnesium sulfate and filtered through silica gel. The filtrate was concentrated to obtain the title compound (7.4 g, 58.3%) as a yellow solid.

X NMR (400 MHz, CDC13) d PPM; 6.27 (2H, s), 7.31 (2H, S) (78b) 1,3-benzodioxol-5,6-diamine Formula 313 A mixture of 5,6-dinitro-l, 3-benzodioxol (7.4 g, 34.9 mmol) obtained in step (78a) above, and 10% palladium carbon (containing 50% water, 1.09 g), methanol (200 ml), and tetrahydrofuran (50 ml) was stirred under a hydrogen atmosphere for 3 days. The reaction mixture was filtered and the filtrate was concentrated to obtain a mixture (6.48 g) containing the title compound as a yellow solid. X NMR (400 MHz, DMSO-d6) d PPM; 4.10 (4H, br s), 5.67 (2H, s), 6.23 (2H, s). (78c) 5H- [1, 3] dioxolo [4,5-f] benzimidazole-6-thiol Formula 314 < The mixture (6.48 g) containing 1,3-benzodioxole-5,6-diamine obtained in step (78b) above was dissolved in methanol (100 ml). To the mixture, carbon disulfide was added (30 ml) and the mixture was stirred at room temperature for one day. The reaction mixture was concentrated under reduced pressure. To the solid residue, ethyl acetate was added and filtration was carried out. The solid was washed through the addition of tetrahydrofuran, ethyl acetate and dilute hydrochloric acid and the insoluble substance was collected by filtration, dried under reduced pressure at room temperature for 2 hours in a desiccator to obtain the title compound (3.8 g, 56.1% of 5,6-dinitro-l, 3-benzodioxol) as a brown solid. * H NMR (400 MHz, DMSO-d6) d PPM; 5.99 (2H, s), 6.74 (2H, s), 12.36 (2H, br s). Sodium salt of (78d) 6- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -5H- [1,3] dioxolo [4,5-f] benzimidazole Formula 315 The same procedure as in steps (5f) to (5h) of Example 5 was repeated using (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2- il) methanol obtained in step (12b) above and 5H- [1, 3] dioxolo [4, 5-f] benzimidazole-6-thiol obtained in step (78c) above to obtain the title compound (347 mg, total 51.9% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.32 (3H, s), 1.34 (3H, s), 2.03-2.13 (lH, m), 2.16 (3H, s), 3.71-3.81 (2H, m), 3.93-4.02 (2H, m), 4.09 ( 2H, d, J = 7 Hz), 4.30 (1H, d, J = 13 Hz), 4.80 (1H, d, J = 13 Hz), 5.82 (2H, s), 6.89 (2H, s), 6.92 ( 1H, d, J = 6 Hz), 8.26 (1H, d, J = 6 Hz). EXAMPLE 79 Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -6,7-dihydro- 1H- [1,4] dioxino [2, 3-f] benzimidazole Formula 316 (79a) 4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -N, N-diisopropylpyridine-2-carboxamide Formula 317 A mixture of 4-chloro-N, N-diisopropylpyridine-2-carboxamide (5 g, 20.8 mmol) obtained in the same manner as in step (92a), (2,2-dimethyl-1,3-dioxan- 5-yl) methanol (3.34 g, 22.8 mmol) obtained in the same manner as in step (lia), potassium hydroxide (2.57 g, 45.8 mmol) and toluene (50 ml) was heated under reflux equipped with a Dean device. Starch for 7 hours and stir at room temperature for 3 days. The reaction mixture was washed with water and a saturated saline solution, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in toluene-heptane-ethyl acetate and subjected to silica gel column chromatography (solvent elution: n-heptane / ethyl acetate = 2 / l- > l / l). The fraction containing a desired product was concentrated and the solid residue was washed with heptane and collected by filtration to obtain the title compound (5.39 g, 73.9%) as a white solid. Xl NMR (400 MHz, DMSO-d 6) [Delta] ppm; 1.09 (6H, d, J = 7 Hz), 1.23 (3H, s), 1.36 (3H, s), 1.43 (6H, d, J = 6 Hz), 2.02-2.10 (1H, m), 3.51-3.65 (2H, m), 3.74 (2H, dd, J = 6, 12 Hz), 3. 98 (2H, dd, J = 4, 12 Hz), 4.16 (2H, d, J = 7 Hz), 6.95-7.00 (2H, m), 8.33 (ÍH, d, J = 6 Hz). (79b) Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -6,7-dihydro -lH- [1,4] dioxino [2, 3-f] benzimidazole Formula 318 The same procedure was repeated in the same way as in steps (92d) and (5f) to (5h) (no reprecipitation step was performed in the oxidation step with 3-chloroperbenzoic acid) using 4- ((2, 2-dimethyl-1,3-dioxan-5-yl) methoxy) -N, N-diisopropylpyridine-2-carboxamide obtained in step (79a) and 6,7-dihydro-lH- [1,] dioxin [2 '] , 3 ': 4,5] benzo [d] imidazole-2-thiol to obtain the title compound (373 mg, total 40.8% yield) as a white solid. X NMR (400 MHz, DMSO-d6) d PPM; 1.30 (3H, s), 1.33 (3H, s), 1.82-1.95 (1H, m), 3.53-3.73 (3H, m), 3.79-3.91 (3H, m), 4.14 (4H, s), 4.38 ( 1H, d, J = 12 Hz), 4.54 (1H, d, J = 12 Hz), 6.55-6.63 (HH, m), 6.74-6.86 (HH, m), 6.83 (2H, s), 8.28 (HH) , d, J = 6 Hz).

Example 80 Sodium salt of 2- (((4- (1,4-dioxaspiro [4.4] non-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 319 (80a) 1,4-dioxaspiro [4.4] nonan-6-carboxylate methyl Formula 320 A X-reflux condenser equipped with a Dean-Stark water separator was attached to a round bottom flask containing methyl 2-cyclopentanonecarboxylate (2 ml, 16.2 mmol), ethylene glycol (994 μl, 17.8 mmol), p-toluenesulfonic acid monohydrate (139 mg, 0.73 mmol), and benzene (30 ml). The mixture was heated under reflux for 2 hours. To the reaction mixture was added triethylamine (0.22 ml) and the mixture was concentrated and purified by silica gel column chromatography (elution solvent: ethyl acetate / heptane = 1/9) to obtain the compound of the title (2.12 g, yield 70.3%) as a colorless oil. Xl NMR (400 MHz, CDC13) d PPM; 1.59-1072 (HH, m), 1077-1.98 (4H, m), 2.06-2.18 (HH, m), 2.93 (1H, t, J = 8 Hz), 3.70 (3H, s), 3.86-4.06 ( 4H, m). (80b) 1,4-dioxaspiro [4.4] non-6-ylmethanol Formula 321 To a suspension of lithium aluminum hydride (630 mg, 16.6 mmol) in diethyl ether (30 ml), 1,4-dioxaspiro [4.4] nonane-6-carboxylic acid methyl ester (3.1 g, 16.6 mmol) obtained by the method of step (80a) before 0 ° C. The mixture was stirred at room temperature for 3 hours. Water (0.6 ml), 5N of aqueous sodium hydroxide solution (0.6 ml), and water (1.8 ml) at 0 ° C were added sequentially to the mixture and the mixture was filtered. Then water was added to the filtrate and the organic layer was separated. The aqueous layer was extracted three times with ethyl acetate. The resulting extract was dried over sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (elution solvent: ethyl acetate / heptane = 1/4) to obtain the title compound. titre (1.9 g, yield 72.4%) as a colorless oil.

Xl NMR (400 MHz, CDC13) d PPM; 1.51-1.92 (6H, m), 2.11-2.18 (HH, m), 2.53-2.69 (HH, br), 3.58-3.73 (2H, m), 3.88-4.02 (4H, m). (80c) 2- (((4- (1,4-dioxaspiro [4.4] non-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula The same procedure as in steps (14a) a (14e) of Example 14 was repeated using 1,4-dioxaspiro [4.4] non-6-ylmethanol obtained in step (80b) above to obtain the title compound (383 mg, total yield of 5 steps: 14.6%) as a light yellow solid. Note that in the same procedure as in step (14c), methanol was used as a solvent instead of ethanol. X NMR (400 MHz, DMSO-d6) d PPM; 1.42-1.80 (5H, m), 1. 86-2.0K1H, m), 2.15 (3H, d, J = 7 Hz), 2.28-2.41 (ÍH, m), 3. 70-3.93 (5H, m), 4.02-4.13 (ÍH, m), 4.38 (1H, d, J = 13 Hz), 4. 77 (1H, d, J = 13 Hz), 6.79-6.87 (2H, m), 6.89 (1H, dd, J = 2.6 Hz), 7.37-7.46 (2H, m), 8.25 (1H, d, J = 6 Hz).

EXAMPLE 81 Sodium salt of 2- (((4- ((3,3-dimethyl-l, 5-dioxaspiro [5.5] undec-9-yl) oxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 323 (81a) 3, 3-dimethyl-l, 5-dioxaspiro [5.5] undecan-9-ol Formula 324 To the suspension of lithium aluminum hydride (748 mg, 19.7 mmol) in tetrahydrofuran (40 ml), a solution of tetrahydrofuran of 1,4-cyclohexanedione mono-2,2-dimethyltrimethylene ketal (3.9 g, 19.7 mmol) was added. at 0 ° C. The mixture was stirred at room temperature for 3 hours. Then water (0.7 ml), 5N of aqueous sodium hydroxide solution (0.7 ml), and water (2.1 ml) were added sequentially at 0 ° C to the mixture, the mixture was dried over sodium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography (elution solvent: ethyl acetate / heptane = 1/2, 1/1, 2/1) to obtain the title compound (3.6 g , yield: 91.2%) as a colorless oil. X NMR (400 MHz, CDC13) d PPM; 0.97 (6H, s), 1.51-1.60 (4H, m), 1.74-1.86 (2H, m), 2.04-2.14 (2H, m), 3.50 (4H, d, J = 4 Hz), 3.74-3.84 ( ÍH, m). (81b) Sodium salt of 2- (((4- ((3,3-dimethyl-l, 5-dioxaspiro [5.5] undec-9-yl) oxy) -3-methylpyridin-2-yl) methyl) sulfinil ) -benzimidazole Formula 325 The same procedure as in steps (14a) to (14e) of Example 14 was repeated using 3, 3-dimethyl-l, 5-dioxaspiro [5.5] undecan-9-ol obtained in step (81a) above to obtain the title compound (275 mg, total yield of 5 steps: 3.3%) as a white solid. Observe that in the same procedure as in step (14b), after adding acetic anhydride, 10 triethylamine equivalents relative to pyridine 1-oxide to carry out the reaction. In the same procedure as step (14c), tetrahydrofuran was used as a solvent instead of ethanol. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.90 (6H, s), 1.62-1.94 (8H, m), 2.18 (3H, s), 3.45 (4H, d, J = 6 Hz), 4.35 (1H, d, J = 13 Hz), 4.70-4.78 (ÍH, br), 4.81 (1H, d, J = 13 Hz), 6.81-6.88 (2H, m), 6.97 (1H, d, J = 6 Hz), 7.39-7.46 (2H, m), 8.23 ( 1H, d, J = 6 Hz). Example 82 Sodium salt of 2- (((4- (1,4-dioxaspiro [4.5] dec-8-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 326 (82a) 1,4 -dioxaspiro [4.5] dec-8-ylmethanol Formula 327 A reflux condenser equipped with a separator of Dean-Stark water was fixed to a round bottom flask containing ethyl 4-cyclohexanonecarboxylate (5 ml, 31.4 mmol), ethylene glycol (1.93 ml, 34.5 mmol), p-toluenesulfonic acid monohydrate (200 mg, 1.05 mmol), and benzene (30 ml). The mixture was heated under reflux for 3 hours. To the reaction mixture was added triethylamine (181 μL, 1.3 mmol) and the mixture was concentrated. A solution of tetrahydrofuran was added to the resulting crude substance to a suspension of tetrahydrofuran (30 ml) of lithium aluminum hydride (1.31 g, 34.5 mmol) at 0 ° C. After the mixture was stirred at room temperature for 7 hours, water (1.3 ml), 5N of aqueous sodium hydroxide solution (1.3 ml), and water (3.9 ml) were added sequentially to the mixture at 0 ° C. After drying over sodium sulfate, the mixture was filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (elution solvent: ethyl acetate / heptane = 1/2, 1/1, 2/1) to obtain the title compound (4.6 g, yield: 85.1%) as a colorless oil. H NMR (400 MHz, CDC13) d PPM; 1.20-1.33 (3H, m), 1. 48-1.6K2H, m), 1.74-1.82 (4H, m), 3.49 (2H, t, J = 6 Hz), 3.92-3.96 (4H, m). Sodium salt from (82b) 2- (((4- (1,4-dioxaspiro [4.5] dec-8-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 328 The same procedure as in steps (14a) to (14b) of Example 14 and steps (7d) to (7f) of Example 7 was repeated using 1, 4-dioxaspiro [4.5] dec-8-ylmethanol obtained in the step (82a) above to obtain the title compound (115 mg, total yield of 5 steps: 7.3%) as a white solid. Note that, in the same procedure as in step (14b), after adding the acetic anhydride, 2 equivalents of triethylamine were added relative to the 1-pyridine oxide to carry out the reaction. 1 H NMR (400 MHz, DMSO-d 6) d PPM; 1.23-1.55 (4H, m), 1.65-1.89 (5H, m), 2.19 (3H, s), 3.81-3.95 (6H, m), 4.36 (1H, d, J = 13 Hz), 4.83 (1H, d, J = 13 Hz), 6.79-6.88 (2H, m), 6.90 (1H, d, J = 6 Hz), 7.38-7.46 (2H, m), 8.24 (1H, d, J = 6 Hz). Example 83 Sodium salt of 2- (((4- (5, 9-dioxaspiro [3.5] non-7-yloxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 329 (83a) 4- (5,9-dioxaspiro [3.5] non-7-yloxy) -N, N-diisopropylpyridine-2-carboxamide Formula 330 The same procedure of step (92c) of Example 92 was repeated using 5,9-dioxaspiro [3.5] nonan-7-ol separately obtained in the method of steps (9a) to (9e) of Example 9, and 4-chloro-N, N-diisopropylpyridine-2-carboxamide obtained in the method of step (92a) of Example 92 to obtain the title compound (1.69 g, 97% yield) as a colorless oil. XH NMR (400 MHz, CDC13) d PPM; 1.12-1.31 (6H, d, J = 6 Hz), 1.74-1.82 (2H, m), 2.24-2.34 (4H, m), 3.45-3.63 (HH, m), 3.72-3.87 (HH, m), 3.90 (2H, dd, J = 5, 12 Hz), 4.05-4.15 (2H, m), 4.36-4.44 (HH, m), 6.88 (1H, dd, J = 2.6 Hz), 6.95 (1H, d, J = 2 Hz), 8.40 (ÍH, d, J = 6 Hz). (6H was missing since it was overlapped with the peak of an H20 content containing 1.4-1.7 ppm) (83b) (4- (5,9-dioxaspiro [3.5] non-7-yloxy) pyridin-2-yl) methanol Formula 331 To a solution of tetrahydrofuran (60 ml) of 4- (5,9-dioxaspiro [3.5] non-7-yloxy) -N, N-diisopropylpyridine-2-carboxamide (1.69 g, 4.85 mmol) obtained in step (83a) ), lithium aluminum hydride (552 mg, 14.5 mmol) was added at -6 to -5 ° C and then the mixture was stirred at room temperature for one hour. Sequentially added water (0.55 ml), 5N of aqueous sodium hydroxide solution (0.55 ml), and water (1.65 ml) to the mixture. After drying over sodium sulfate, the mixture was concentrated under reduced pressure, and purified by silica gel column chromatography (eluant solvent: heptane, ethyl acetate / heptane = 1 / l, ethyl acetate) to obtain the compound of the title (560 mg, yield 45.9%) as a white solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.65 (2H, quint, J = 8 Hz), 2.14 (2H, t, J = 8 Hz), 2.23 (2H, t, J = 8 Hz), 3.77 (2H, dd, J = 3, 13 Hz), 3.99-4.06 (2H, m), 4.44-4.49 (3H, m), 6.82 (1H, dd, J = 2, 6 Hz), 6.96 (1H, d, J = 2 Hz ), 8.25 (1H, d, J = 6 Hz). (83c) 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 332 The same procedure as in steps (9h) to (9j) of Example 9 was repeated using te (4- (5,9-dioxaspiro [3.5] non-7-yloxy) pyridin-2-yl) methanol obtained in step (83b) above to obtain the title compound (100 mg, total 3 step yield: 50%) as a white solid. Note that, in the same procedure as in step (9h), 2-mercaptobenzimidazole was added to the reaction mixture and stirred at room temperature for 25 hours, and then 3 equivalents of potassium hydroxide were added thereto. relationship to alcohol. The mixture was allowed to react at room temperature for 6 hours. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.56-1.70 (2H, m), 2.04-2.24 (4H, m), 3. 4-3.53 (ÍH, m), 3.60-3.72 (2H, m), 3. 80 (1H, dd, J = 2, 13 Hz), 3.96 (1H, t, J = 2 Hz), 4.41 (1H, d, J = 12 Hz), 4.57 (1H, d, J = 12 Hz), 6.55 (1H, d, J = 3 Hz), 6.81-6.91 (3H, m), 7.40-7.48 (2H, m), 8.31 (1H, d, J = 6 Hz). Example 84 Sodium salt of 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -5-fluoro-benzimidazole Formula 333 (84a) 2, 2-diethoxyethylbenzoate Formula 334 To a solution of pyridine (30 ml) of glycol aldehyde diethyl acetal (19.8 g, 148 mmol), benzoyl chloride (51.7 ml, 444 mmol) of -20 to 30 ° C was added dropwise.

The mixture was stirred at room temperature for 167 hours and 50 minutes. After adding methanol and water to the mixture, performed the extraction with ethyl acetate. The organic layer obtained was washed with a saturated aqueous solution of ammonium chloride, saturated aqueous solution of sodium acid carbonate, and a saturated saline solution. After drying over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography (elution solvent: heptane, ethyl acetate / heptane = 1/9). The purification was then carried out again by silica gel column chromatography (eluant solvent: heptane, ethyl acetate / heptane = 1/100, 1/30, 1/10) to obtain the title compound ( 34 g, yield: 96.4%) as a light green oil. Xl NMR (400 MHz, CDC13) d PPM; 1.24 (6H, t, J = 7 Hz), 3.58-3.68 (2H, m), 3.72-3.82 (2H, m), 4.34 (2H, d, J = 6 Hz), 4.83 (1H, t, J = 6 Hz), 7.42-7.48 (2H, m), 7.54-7.60 (HH, m), 8.02-8.09 (2H, m). (84b) benzoate , 7-dioxaspiro [2.5] oct-6-ylmethyl Formula 335 A reflux condenser equipped with a separator of Dean-Stark water was fixed to a round bottom flask containing 2,2-diethoxyethyl benzoate (33 g, 139 mmol) obtained in step (84a) above, 1,1-bis (hydroxymethyl) cyclopropane (15.6 g, 153 mmoles), p-toluenesulfonic acid monohydrate (2.64 g, 13.9 mmol), and toluene (100 ml). The mixture was heated under reflux for 2 hours and cooled to room temperature. To the reaction mixture was added triethylamine (10 ml), ethyl acetate (100 ml), and silica gel (50 g). The mixture was concentrated and purified by silica gel column chromatography (elution solvent: ethyl acetate / heptane = 1/30, 1/10) to obtain the title compound (25.5 g, 73.9% yield) as an oil. light yellow. Xl NMR (400 MHz, CDC13) d PPM; 0.32-0.39 (2H, m), 0.68-0.76 (2H, m), 3.29 (2H, d, J = 12 Hz), 4.16 (2H, d, j = 12 Hz), 4.41 (2H, d, J = 5 Hz), 4.98 (1H, t, J = 5 Hz), 7.40-7.46 (2H, m), 7.52-7.58 (HH, m), 8.04-8.09 (2H, m). (84c) 5,7-dioxaspiro [2.5] oct-6-ylmethanol Formula 336 To a mixture of 5,7,7-dioxaspiro [2.5] oct-6-ylmethyl benzoate (25.1 g, 101 mmol) obtained in step (84b) above and methanol (150 ml), 2N of aqueous solution was added. of sodium hydroxide (55.6 ml, 111 mmol) at an internal temperature of 0 to 4 ° C. After the mixture was stirred at room temperature for 3 hours, a saturated aqueous solution of ammonium chloride was added to the mixture to adjust the pH to about 9. The mixture was concentrated under reduced pressure to approximately the amount of methanol. Ethyl acetate was added to the residue and the organic layer was separated. The aqueous layer was extracted with ethyl acetate and then sodium chloride was added to the obtained water layer. The mixture was extracted with ethyl acetate and then the organic layers were combined and washed with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and then the solvent was removed by distillation to obtain the title compound (10 g, yield: 68.6%) as a colorless oil. X NMR (400 MHz, CDC13) d PPM; 0.33-0.37 (2H, m), 0.68-0.72 (2H, m), 1.87 (1H, t, J = 6 Hz), 3.28 (2H, d, J = ll Hz), 3.68 (2H, dd, J = 4, 6 Hz), 4.16 (2H, d, J = ll Hz), 4.73 (1H, t, J = 4 Hz). Sodium salt from (84d) -2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -5-fluoro-benzimidazole Formula 337 The same procedure of step (79a) of Example 79, step (92d) of Example 92, step (5f) of Example 5, and steps (9i) to (9j) of Example 9 was repeated using tea 5, 7 -dioxaspiro [2.5] oct-6-ylmethanol obtained in step (84c) above to obtain the title compound (298 mg, total yield of 5 steps: 14.1%) as a white solid. Note that in the same operation as in step (92d), ethanol was used instead of methanol. In the same operation as in step (5f), 5-fluoro-benzimidazole-2-thiol obtained in step (52a) of Example 52 was used in place of 2-mercaptobenzimidazole. Xl NMR (400 MHz, DMSO-d6) d PPM; 0.33 (2H, dd, J = 7, 8 Hz), 0.59 (2H, dd, J = 7, 8 Hz), 3.24 (2H, d, J = 12 Hz), 3.92-4.04 (2H, m), 4.09 (2H, d, J = 12 Hz), 4.43 (1H, d, J = 12 Hz), 4.50 (1H, d, J = 12 Hz), 4.94 (1H, t, J = 4 Hz), 6.64-6.78 (HH, m), 6.80-6.98 (2H, m), 7.16 (1H, dd, J = 2, 10 Hz), 7.42 (1H, d, J = 5, 8 Hz), 8.37 (HH, d, J = 6 Hz).

Example 85 Sodium salt of 2- (((4- (6,8-dioxaspiro [3.5] non-7-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 338 (85a) Cyclobutane-1, 1-diyl dimethanol Formula 339 A solution of tetrahydrofuran (50 ml) of diethyl 1,1-cyclobutanedicarboxylate (4.97 g, 24.8 mmol) was cooled under ice-cooling. To the solution, lithium aluminum hydride (1.6 g, 42.2 mmol) was added. The reaction mixture was stirred at 0 ° C for 10 minutes and further stirred at room temperature for 15 minutes. The reaction was terminated by the addition of diethyl ether-water to the reaction mixture. The solution having the precipitated inorganic compounds was dried over anhydrous magnesium sulfate and The solvent was distilled under reduced pressure to obtain the title compound (2.88 g, 100%) as a colorless oil. H NMR (400 MHz, CDC13) d PPM; 1.77-1.82 (4H, m), 1. 90-1.96 (2H, m), 2.38 (2H, br s), 3.75 (4H, s). (85b) 7- ((benzyloxy) methyl) -6,8-dioxaspiro [3.5] nonane Formula 340 A mixture of cyclobutan-1,1-diyldimethanol (2.88 g, 24.8 mmol) obtained in step (85a) above, benzyloxyacetaldehyde (3.72 g, 24.8 mmol), p-toluenesulfonic acid monohydrate (214 mg, 1.13 mmol) and toluene ( 70 ml) was heated under reflux for one hour while the water was removed through a Dean-Stark apparatus. The reaction mixture was cooled to room temperature and triethylamine (3 ml) was added thereto, then the solvent was distilled off. The residue was purified by silica gel column chromatography (silica gel: 200 g, eluting solvent: ethyl acetate / heptane = 1 / 50-> 1/9) to obtain the title compound (3.8 g, yield). : 48.7%) as a white solid. Xl NMR (400 MHz, CDC13) [delta] ppm; 1.54 (2H, t, J = 8 Hz), 1.90 (2H, quint, J = 8 Hz), 2.10 (2H, t, J = 8 Hz), 3.49 (2H, d, J = 4 Hz), 3.52 (2H, d, J = ll Hz) , 4.00 (2H, d, J = ll Hz), 4.57 (2H, s), 4.67 (1H, t, J = 4 Hz), 7.25-7.33 (5H, m). (85c) 6, 8-dioxa spiro [3.5] non-7-ylmethanol Formula 341 A mixture of 7- (benzyloxy) methyl) -6,8-dioxaspiro [3.5] nonane (3.8 g, 15.3 mmol) obtained in step (85b) above, 20% palladium hydroxide (800 mg), and ethyl acetate (70 ml) was stirred under a hydrogen atmosphere overnight. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration. The filtrate was concentrated to obtain the title compound (2.0 g, yield: 82.6%) as a white solid. Xl NMR (400 MHz, CDC13) d PPM; 1.56 (2H, t, J = 8 Hz), 1.83 (1H, t, J = 4 Hz), 1.92 (2H, quint, J = 8 Hz), 2.10 (2H, t, J = 8 Hz), 3.54 ( 2H, d, J = ll Hz), 3.60 (2H, t, J = 5 Hz), 4.02 (2H, d, J = ll Hz), 4.56 (1H, t, J = 4 Hz). (85d) 2- (((4- (6,8-dioxaspiro [3.5] non-7-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole sodium salt Formula 342 The same method was repeated as in steps (62c) and (8d) to (8g) using alcohol obtained in step (85c) above to obtain the title compound (198 mg, total yield 13.6%) as a white solid. 1ti NMR (400 MHz, DMSO-d6) d PPM; 1.51 (2H, t, J = 8 Hz), 1.85 (2H, quint, J = 8 Hz), 1.98 (2H, t, J = 8 Hz), 2.16 (3H, s), 3.54 (2H, d, J = 10 Hz), 3.97 (2H, d, J = 10 Hz), 4.01 (2H, d, J = 4 Hz), 4.38 (1H, d, J = 13 Hz), 4.76 (1H, d, J = 13 Hz), 4.86 (1H, t, J = 4 Hz), 6.83-6.85 (2H, m), 6.92 (1H, d, J = 6 Hz), 7.41-7.43 (2H, m), 8.25 (ÍH, d , J = 6 Hz). Example 86 Sodium salt of 2 - (((4- (2- (5,5-dimethyl-1,3-dioxan-2-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 343 The same procedure as in steps (lc) to (lg) of Example 1 was repeated using 5, 5-dimethyl-1,3-dioxane-2-ethanol (1.00 g, 6.24 mmol) to obtain the title compound (138 mg, 0.31 mmol) as a cream colored solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 0.68 (3H, s), 1.09 (3H, s), 1.96-2.07 (2H, m), 2.16 (3H, s), 3.41 (2H, d, J = ll Hz), 3.53 (2H, d, J = ll Hz), 4.10 (2H, t, J = 6 Hz), 4.38 (1H, d, J = 13 Hz), 4.65 (1H, t, J = 5 Hz), 4.74 (1H, d, J = 13 Hz ), 6.79-6.88 (2H, m), 6.90 (1H, d, J = 6 Hz), 7.38-7.47 (2H, m), 8.25 (1H, d, J = 6 Hz). Example 87 Sodium salt of 2- (((4- (1, 3-dioxolan-4-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 344 The same procedure as in steps (lc) to (1 g) of Example 1 was repeated using glycerol formal (1.76 ml, 20.3 mmol) to obtain the title compound (87 mg, 0.22 mmol) as a cream solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 2.18 (3H, s), 3.68-3.74 (1H, m), 4.01 (1H, t, J = 8 Hz), 4.06-4.17 (2H, m), 4.33- 4. 43 (2H, m), 4.78 (1H, d, J = 3 Hz), 4.85 (1H, s), 4.94 (1H, s), 6.78-6.88 (2H, m), 6.93 (1H, d, J = 6 Hz), 7.36-7.46 (2H, m), 8.26 (1H, d, J = 6 Hz). EXAMPLE 88 Sodium salt of an optical isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin -2-yl) methyl) sulfinyl) -benzimidazole Formula 345 Na Another synthesis method performed in Example 20 is described below. (88a) Optical Isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -benzimidazole Formula 346 A toluene solution (4 ml) of 2 - (((4- (2,2- dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole (500 mg, 1.21 = moles), zirconium complex (IV) isopropoxide isopropanol (295 mg, 0.76 mmoles) and N, N, N ', N' - (-) - tetramethyl- (D) -tartaramide (396 mg, 1.94 mmol) was stirred under a nitrogen atmosphere at 40 ° C for one hour. After the solution was cooled to room temperature, N, N-diisopropylethylamine (91 μl, 0.52 mmole) was added and subsequently, eumeno hydroperoxide (243 μl, 1.32 mmoles according to the content was estimated as 80%) was added dropwise to the The mixture was then stirred at room temperature for 22 hours. After a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium thiosulfate were added, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 30 g, solvent elution: ethyl acetate, ethyl acetate / methanol 7: 3, 1, 1 gradient). The fractions containing the title compound were collected with ethyl acetate and concentrated to obtain the title compound (328 mg, yield: 63%) as a colorless foam. HPLC (Conditions) column: CHIRALPAK IA (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = 3/2 (v / v), speed flow: 0.5 ml / min, detection: UV (254 nm). (Results of the Analysis) The retention time: 17.5 minutes, enantiomeric excess: 99% ee. (88b) Sodium salt of an optical isomer (Short in retention time) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin -2-yl) methyl) sulfinyl) -benzimidazole Formula 347 The same procedure as in Example 20b was repeated to form a sodium salt of to obtain the title compound (299 mg, yield: 88%) as a white solid. HPLC (Conditions) column: CHIRALPAK IA (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = 3/2 (v / v), flow rate: 0.5 ml / min, detection: UV (254 nm). (Results of the Analysis) The retention time: 18.0 minutes, excess enantiomeric: 99% ee. Rotation Specifies: aA 22. ' = + 78.51 (c = 0.5, EtOH) Example 89 Sodium salt of an optical isomer (Short in retention time) of 2- (((4- ((2, 2-dimethyl-l, 3-dioxan-5- il) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 348 Na Another synthesis method performed in Example 20 is described below. (89a) Optical Isomer (Short in retention time) of 2 - (((4 - ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -benzimidazole Formula 349 A mixture of 2- (((4- ((2, 2-dimethyl-l, 3-dioxan-5- il) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole (500 mg, 1.21 mmoles) and N, N, N ', N' - (-) - tetramethyl- (D) -tartaramide (396 mg, 1.94 mmol) in toluene (4 ml) was dissolved by heating at 40 ° C. for 10 minutes in a nitrogen atmosphere. Hafnium tetrabutoxide was added (315 μl, 0.78 mmol) to the mixture and further stirred at the same temperature for one hour. After the reaction mixture was cooled to room temperature, N, N-diisopropylethylamine (90 μl, 0.52 mmole) was added and subsequently, eumeno hydroperoxide (267 μl, 1.46 mmole according to the content was estimated as 80%) was added by drip to the mixture and then the mixture was stirred at room temperature for 22 hours. After a saturated aqueous solution of sodium acid carbonate and a saturated aqueous solution of sodium thiosulfate were added, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 30 g, solvent elution: ethyl acetate, ethyl acetate / methanol 7: 3, 1; 1 gradient). The fractions containing the title compound were collected with ethyl acetate and concentrated to obtain the title compound (206 mg, yield: 40%) as a colorless foam. HPLC (Conditions) column: CHIRALPAK IA (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = 3/2 (v / v), flow rate: 0.5 ml / min, detection: UV (254 nm). (Results of the Analysis) The retention time: 17.2 minutes, enantiomeric excess: 90% ee. (89b) Sodium salt of an optical isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5- dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 350 The same procedure as in Example 20b was repeated to form a sodium salt of to obtain the title compound (182 mg, yield: 84%) as a white solid. HPLC (Conditions) column: CHIRALPAK IA (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = 3/2 (v / v), flow rate: 0.5 ml / min, detection: UV (254 nm).

(Results of the Analysis) The retention time: 18.1 minutes, enantiomeric excess: 89% ee. EXAMPLE 90 Optical Isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 351 Another synthesis method performed in Example 20a is described below In a flask, (S) - (-) -2- (3,5-di-tert-butylsalicylideneamino) -3,3-dimethyl-1-butanol was added. (115 mg, 0.35 mmol), vanadyl acetylacetone (64 mg, 0.24 mmol), and acetonitrile (0.8 ml) and the mixture was stirred at room temperature for 30 minutes. The mixture was added to a dichloromethane solution (3 ml) of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-dichloromethane. il) methyl) thio) -benzimidazole (500 mg, 1.21 mmol) prepared in another flask, and the resulting mixture was stirred at room temperature for 30 minutes. An aqueous acid peroxide solution (150 μl) was added per means of dividing the quantity of the solution by 15 times (10 μl each time) for 20 hours and the mixture was further stirred for 24 hours. Then, IN of aqueous sodium hydroxide solution (3 ml) was added and the mixture was stirred for 48 hours, a saturated aqueous solution of sodium hydrogen carbonate was added and a saturated aqueous solution of sodium thiosulfate was added to the mixture and then the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (silica gel NH 30 g, elution solvent: ethyl acetate, ethyl acetate / methanol 7: 3, 1; 1 gradient). The fractions containing the title compound were collected with ethyl acetate and concened to obtain the title compound (76 mg, yield: 15%) as a colorless foam. HPLC (Conditions) column: CHIRALPAK IA (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = 3/2 (v / v), flow rate: 0.5 ml / min, detection: UV (254 nm). (Results of the Analysis) The retention time: 19.9 minutes, enantiomeric excess: 45% ee.

EXAMPLE 91 Sodium salt of an optical isomer of 2- (((3-methyl-4- (1, 5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 352 An ethanol solution of a sodium salt of (racemate) of 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -benzimidazole (192 mg) was prepared and separated by HPLC (column: CHIRALCEL OD-H 2 cmfx25 cm (manufactured by Daicel Chemical Industries, Ltd.), mobile phase: ethanol / n-hexane = 3/2, flow rate: 3.0 ml / min, detection wavelength: 254 nm). Immediately after obtaining the fractions, IN of aqueous sodium hydroxide solution (1 ml) was added to each of the fractions. The fractions containing the short and long optical isomers in retention time were respectively collected and separated with ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer of each of the fractions was dried over anhydrous sodium sulfate, concentrated and subjected to azeotropic distillation with diethyl ether.

The short optical isomer residue in retention time was subjected to the same operations as HPLC fraction, separation, drying and concentration as mentioned above. The residue obtained was purified by silica gel column chromatography (silica gel NH 20 g, eluting solvent: dichloromethane, dichloromethane / methanol = 10 / l). Next, the same HPLC fraction, separation, drying, concentration and azeotropic distillation with diethyl ether as mentioned above were performed to obtain a free form of the optical isomer (20 mg) short in retention time as a colorless solid. The residue of the long optical isomer in retention time was subjected to the same HPLC fraction, separation, drying, concentration and previous azeotropic distillation to obtain a free form of the optical isomer (14 mg) long in retention time as a colorless solid. Each of the free optical isomers was subjected to the operation to convert it to a sodium salt of the same form as in step (lli) of Example 11 to obtain a sodium salt of (18 mg) of the short optical isomer in retention time and a sodium salt of (14 mg) of the long optical isomer in retention time, both as a colorless solid. X H NMR (400 MHz, DMSO-d 6); With respect to the sodium salts of both optical isomers, the same were obtained graphs as in the case of the sodium salt of (racemate) of 2- (((3-methyl-4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl sulfinyl) -benzimidazole. HPLC (Conditions) column: CHIRALPAK OD-H (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = 4 / l (v / v), flow rate: 0.5 ml / min, detection : UV: (280 nm). (Results of the Analysis) With respect to the sodium salt of a short optical isomer in retention time, retention time: 36 minutes, enantiomeric excess: > 98.0% us Specific rotation: aD25"5 = + 107.73 (c = 0.32, EtOH) With respect to the sodium salt of a long optical isomer in retention time, retention time: 44 minutes, enantiomeric excess:> 98.0% ee. Specific rotation: aD25-0 = -115.85 (c = 0.19, EtOH) Example 92 Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-ethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 353 (92a) 4-chloro-N, N-diisopropylpyridine-2-carboxamide Formula 354 Thionyl chloride (60 ml, 823 mmol) was diluted with toluene (100 ml) and heated to 45 ° C. To the mixture, N, N-dimethylformamide (16 ml, 207 mmol) was added and the resulting mixture was stirred under the same conditions for one hour. To the mixture, picolinic acid (25 g, 203 mmol) was added and the resulting mixture was stirred at 80 ° C for one hour and 20 minutes. After the reaction mixture was concentrated and diisopropylamine (185 ml, 807 mmol) and acetonitrile (500 ml) were added to the residue, the mixture was stirred at room temperature for 21 hours and 30 minutes. After the reaction mixture was concentrated, the residue was separated with ethyl acetate and water. The organic layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane / acetate of ethyl) to obtain the title compound (31.1 g, yield: 63.6%) as a pale brown solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.11 (6H, d, J = 7 Hz), 1.43 (6H, d, J = 6 Hz), 3.54-3.66 (2H, m), 7.56-7.62 (2H, m), 8.51-8.56 (1H, m) . (92b) 4-chloro-3-ethyl-N, N-diisopropylpyridine-2-carboxamide Formula 355 To a solution of tetrahydrofuran (dehydrated) (50 ml) of diisopropylamine (1.35 g, 13.3 mmol), n-butyllithium (1.6 M hexane solution, 6.75 ml, 10.8 mmol) was added dropwise under cooling with ice under a nitrogen atmosphere and the resulting mixture was stirred under the same conditions for 30 minutes. After the reaction mixture was cooled to -70 ° C, a tetrahydrofuran solution of 4-chloro-N, N-diisopropylpyridine-2-carboxamide (2 g, 8.31 mmol) obtained in step (92a) above was added. mixture and the resulting mixture was stirred at -70 ° C for 1.5 hours. To the reaction mixture was added ethyl iodide (798 μl, 10 mmol) and the resulting mixture was stirred at -70 ° C at 0 ° C for 3 hours. To the reaction mixture was added, a saturated aqueous solution of ammonium chloride was added and extracted with ethyl acetate. ethyl. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluant solvent: heptane / ethyl acetate) to obtain the title compound (1.9 g, yield: 85.1%) as a light yellow solid. Xl NMR (400 MHz, CDC13) d PPM; 1.15 (6H, d, J = 7 Hz), 1.25 (3, t, J = 7 Hz), 1.58 (6H, d, J = 7 Hz), 2.70-2.84 (2H, m), 3.42-3.60 (2H , m), 7.26 (1H, d, J = 6 Hz), 8.28 (1H, d, J = 6 Hz). (92c) 4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-ethyl-N, N-diisopropylpyridine-2-carboxamide Formula 356 To a solution of dimethyl sulfoxide (20 ml) of 4-chloro-3-ethyl-N, N-diisopropylpyridine-2-carboxamide (1 g, 3.72 mmol) obtained in step (92b) above, oily sodium hydride was added, in oil (195 mg, 4.46 mmoles depending on the content was estimated as 55%) at room temperature. To the mixture was added (2,2-dimethyl-1,3-dioxan-5-yl) methanol (598 mg, 4.09 mmol) obtained in Example (la) and the mixture was stirred at room temperature for 16.5 hours. Ethyl acetate was added to the reaction mixture. The mixture was washed two sometimes with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was washed with diethyl ether to obtain the title compound (520 mg, yield: 36.9%) as a light yellow solid. 1 H NMR (400 MHz, CDC13) d PPM; 1.10-1.22 (9H, m), 1.44 (3H, s), 1.49 (3H, s), 1.58 (6H, d, J = 7 Hz), 2.14-2.22 (ÍH, m), 2.55-2.66 (2H, m), 3.46-3.60 (2H, m), 3.86-3.98 (2H, m), 4.10-4.26 (4H, m), 6.77 (1H, d, J = 6 Hz), 8.32 (1H, d, J = 6 Hz). (92d) (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-ethylpyridin-2-yl) methanol Formula 357 To a solution of tetrahydrofuran (10 ml) of 4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3-ethyl-N, N-diisopropylpyridine-2-carboxamide (520 mg, 1.37 mmoles) obtained in step (92c) above, lithium aluminum hydride (156 mg, 4.11 mmol) was added under ice-cooling and the mixture was stirred under ice-cooling for one hour. To the reaction mixture, water (0.2 ml) was added sequentially, to 2N aqueous sodium hydroxide solution (0.2 ml), and water (0.6 ml). Then, the mixture was filtered through celite and solvent was distilled off from the filtrate under reduced pressure. To a methanol solution (20 ml) of the residue, sodium borohydride (51.8 mg, 1.37 mmol) was added and the mixture was stirred at room temperature for one hour. A saturated saline solution was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated to obtain a crude product of the title compound (456 mg, yield: 118%) as a light yellow solid. XH NMR (400 MHz, CDC13) d PPM; 1.09 (3H, t, J = 7 Hz), 1.43 (3H, s), 1.49 (3H, s), 2.14-2.22 (HH, m), 2.52 (2H, q, J = 7 Hz), 3.90 (2H , dd, J = 5, 12 Hz), 4.08-4.22 (4H, m), 4.71 (2H, s), 6.76 (1H, d, J = 6 Hz), 8.31 (1H, d, J = 6 Hz) . (92e) Sodium salt of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3-ethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 358 The same procedure as in steps (6d), (6e), and (6f) of Example 6 was repeated using te (4- ((2, 2- dimeti1-1, 3-dioxan-5-yl) methoxy) -3-ethylpyridin-2-yl) methanol obtained in step (92d) above to obtain the title compound (159 mg, overall yield: 25%) as a light yellow solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.07 (3H, t, J = 7 Hz), 1. 33 (3H, s), 1.35 (3H, s), 2.06-2.16 (HH, m), 2.62-2.82 (2H, m), 3.78 (2H, dd, J = 6, 12 Hz), 3.98 (2H, dd, J = 4, 12 Hz), 4.09 (2H, d, J = 10 Hz), 4.36 (1H, d, J = 13 Hz), 4.77 (1H, d, J = 13 Hz), 6.80-6.98 ( 2H, m), 6.93 (1H, d, J = 6 Hz), 7.38-7.48 (2H, m), 8.28 (H, d, J = 6 Hz). EXAMPLE 93 Sodium salt of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -6 , 7-dihydro-lH- [1,4] dioxino [2, 3-f] benzimidazole Formula 359 The same procedure as in steps (5f) to (5h) was repeated using te (4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2- il) methanol, which was obtained by subjecting (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methanol monohydrate obtained in the same as Example 96 (5) to azeotropic distillation with toluene, and 6,7-dihydro-lH- [1, 4] dioxino [2 ', 3': 4,5] benzo [d] imidazole-2-thiol , to obtain the title compound (395 mg, total 61.7% yield) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.32 (3H, s), 1.35 (3H, s), 2.00-2.13 (HH, m), 2.18 (6H, s), 3.69-3.86 (4H, m), 3.91-4.03 (2H, m), 4.14 ( 4H, s), 4.31 (1H, d, J = 12 Hz), 4.70 (1H, d, J = 12 Hz), 6.82 (2H, s), 8.19 (1H, s). Example 94 Sodium salt of 2- (((3-Methyl-4- (2- (8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) - 6, 7-dihydro-1H- [1,4] dioxino [2, 3-f] benzimidazole Formula 360 The same procedure as in steps (5d) to (5h) was repeated using 2- (8-methyl-1, 4, 7, 9-tetraoxaspiro [4.5] dec-8-yl) ethanol and 6,7-dihydro -lH- [1,4] dioxino [2 ', 3': 4,5] benzo [d] imidazole-2-thiol obtained in Example (73b) to obtain the title compound (110 mg, content: 93.5%, total 9.2% yield) as a solid White. Xl NMR (400 MHz, DMSO-d) d PPM; 1.39 (3H, s), 2.05-2.23 (5H, m), 3.56-3.72 (4H, m), 3.75-3.93 (4H, m), 4.02-4.22 (6H, m), 4.31 (1H, d, J = 13 Hz), 4.75 (1H, d, J = 13 Hz), 6.82 (2H, s), 6.88 (1H, d, J = 5 Hz), 8.24 (1H, d, J = 5 Hz). EXAMPLE 95 Sodium salt of 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -6,7-dihydro-lH- [1,4] dioxin [2, 3-f] benzimidazole Formula The same procedure as in steps (5f) to (5h) was repeated using te (4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methanol obtained in Example ( 2d) and 6,7-dihydro-lH- [1,4] dioxino [2 ', 3':, 5] benzo [d] imidazole-2-thiol to obtain the title compound (364 mg, total 55.6% yield ) as a light pink solid. X H NMR (400 MHz, DMS0-d 6) [delta] ppm; 0.26-0.40 (2H, m), 0.50-0.66 (2H, m), 2.16 (3H, s), 3.26 (2H, d, J = 12 Hz), 4.09 (2H, d, J = 4 Hz), 4.12 (2H, d, J = 12 Hz), 4.15 (4H, s), 4.33 (1H, d, J = 13 Hz), 4.76 (1H, d, J = 13 Hz), 5.02 (1H, t, J = 4 Hz), 6.83 (2H, s), 6.94 (1H, d, J = 6 Hz), 8.26 (1H, d, J = 6 Hz). EXAMPLE 96 Sodium salt of an optical isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin -2-yl) methyl) sulfinyl) -benzimidazole Formula 362 (1) Optical isomer (short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -benzimidazole (429 mg, 1 mmol) was dissolved in ethanol (0.85 ml) and INN of aqueous sodium hydroxide solution (1 ml, 1 mmol) was added thereto. After the mixture was concentrated under reduced pressure and ethanol (0.85 ml) was added thereto, the mixture was concentrated under reduced pressure. Tetrahydrofuran (0.85 ml) was added, and then tert-butylmethyl ether (8 ml) was added to make the nebulous mixture (turbid white). After the mixture was allowed to stand at room temperature overnight, the generated precipitate was collected by filtration to obtain the title compound (191 mg, 42% yield) (lot A) as a white solid. (2) Optical isomer (short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -benzimidazole (490 mg, 1.14 mmol, enantiomeric excess: 98% ee) was dissolved in ethanol (0.98 ml) and INN of aqueous sodium hydroxide solution (1.14 ml, 1.14 mmol) was added thereto. . After the mixture was concentrated under reduced pressure and ethanol (0.98 ml) was added thereto, the mixture was concentrated under reduced pressure. This operation was repeated twice. After ethyl acetate (6 ml) was added, the title compound obtained in step (1) (batch A) was added as necessary to the mixture. The mixture was concentrated under reduced pressure. After ethyl acetate (8 ml) was added, the title compound obtained in step (1) (Iota A) was added as a seed to the mixture, the mixture was allowed to stand at room temperature for one hour and 13 minutes. In addition ethyl acetate (2 ml) was added to the mixture, the mixture was allowed to stand at room temperature overnight. The generated precipitate was collected by filtration to obtain the title compound (309 mg, yield 60%) (lot B) as white crystal. (3) To a solution of ethanol (8 ml) solution of an optical isomer (short in retention time) of 2 - (((4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-ylmethyl) sulfinyl) -benzimidazole (4 g, 9.31 mmol), was added IN of aqueous sodium hydroxide solution (9.31 mmoles, 9.31 mmoles) thereto. After the mixture was stirred under the same conditions for 2 hours, the solvent was distilled off under reduced pressure. Ethanol (8 ml) was added to the residue and distilled under reduced pressure. After this operation was repeated twice, ethyl acetate (80 ml) was added to the residue, the title compound (lot B) obtained in step (2) was added with seed crystal and the resulting mixture was allowed to stand at room temperature. Atmosphere during the night. After that, it was left to rest immobile at 4 ° C during the night. The generated precipitate was collected by filtration to obtain the title compound (1.1 g, yield: 25.9%) (lot C) as a light yellow crystal. Part of the solvent of the filtrate thus obtained was distilled under reduced pressure. The resulting crystal, then allowed to stand at room temperature for 2 hours, was collected by filtration to obtain the title compound (2.5 g, yield: 59.5%) (lot D) as a light yellow crystal. (4) To a solution of ethanol (10 ml) of an optical isomer (short in retention time) of 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) ) 3, 5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole (200 mg, 0.466 mmol, enantiomeric excess: 77.1% ee), IN was added aqueous sodium hydroxide solution (466 μl, 0.466 mmol) at room temperature, and then the mixture is concentrated under reduced pressure. After ethanol (10 ml) was added, the mixture was concentrated under reduced pressure. This operation was repeated twice. To the residue, ethyl acetate (40 ml) was added, and the resulting suspension was dissolved in ethanol. The mixture was concentrated under reduced pressure and dissolved in ethyl acetate (4 ml) and ethanol (2 ml). Ten, the title compound (lot D) obtained in step (3) was added as a seed and the mixture was concentrated under reduced pressure. The residue was dissolved in 2-propanol (0.4 ml) and ethyl acetate (4 ml) and then, the title compound (lot D) obtained in step (3) was added as a seed. After it was allowed to stand at room temperature, the mixture was concentrated under reduced pressure. After the resulting mixture was dissolved in ethanol (0.2 ml) and ethyl acetate (3 ml), the title compound (lot D) obtained in step (3) was added at room temperature as a seed with stirring. In about 10 minutes, a precipitate began to emerge. After further stirring for approximately 10 minutes, the generated precipitate was collected by filtration to obtain the title compound (44 mg, 21% yield) (lot E) as a white crystal. (5) Optical isomer (short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl ) methyl) sulfinyl) -benzimidazole (340 mg, 0. 792 mmol, enantiomeric excess, 47% ee) was dissolved in ethanol (4.5 ml) at room temperature and IN of aqueous sodium hydroxide solution (792 μl, 0.792 mmole) was added dropwise thereto. The mixture was concentrated at 40 ° C under reduced pressure. After ethanol (0.9 ml) was added, the mixture was concentrated under reduced pressure. This operation was repeated twice to remove the water azeotropically.

Then ethyl acetate was added to the mixture, the mixture was stirred at room temperature, collected by filtration, and washed with ethyl acetate (4.5 ml) to obtain the title compound (lot F) (230 mg, performance 64. 3%) as a light yellow solid. The filtrate was subjected to the same operation to obtain the title compound (Lot G) (47 mg, yield: 13.1%) as a light yellow solid. HPLC (Conditions) column: CHIRALPAK AD-H (manufactured by Daicel Chemical Industries, Ltd.) (0.46 cmfx25 cm) eluent: hexane / ethanol = l / l (v / v), flow rate: 0.6 ml / min, detection : UV 254 nm). (Results of the Analysis) Lot B: retention time: 16.7 minutes, enantiomeric excess: 100% ee; Lot C: retention time: 17.2 minutes, enantiomeric excess: 100% ee; Lot D: retention time: 16.8 minutes, enantiomeric excess: 100% ee; Lot E: retention time: 18.0 minutes, enantiomeric excess: 100% ee; Lot F: retention time: 17.1 minutes, enantiomeric excess: 39% ee; Lot G: retention time: 17.1 minutes, enantiomeric excess: 62% ee. EXAMPLE 97 Sodium salt of an optical isomer (Short in retention time) of 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin -2-yl) methyl) sulfinyl) -benzimidazole (1) 2, 3, 5-trimethylpyridine, Formula 363 It was added to acetic acid (1.43 kg, 23.83 moles), 2, 3, 5-trimethylpyridine (1.43 kg, 11.80 moles) for 15 minutes. After 15 minutes, a solution of 35% acidic peroxide (1.38 kg, 14.2 moles) was added dropwise for 30 minutes, the mixture was stirred at 90 ° C at 95 ° C overnight. Sodium sulfite (220 g) was added to the reaction mixture. The reaction mixture was poured into a mixture of Sodium carbonate (2.5 kg) and water (12 L) and the mixture was extracted with chloroform (3.0 L x 4). The organic layer obtained was concentrated until a crystal precipitated. The n-hexane (2.5 L) was added to the precipitate. The resulting mixture was stirred under ice-cooling overnight. The resulting solid was filtered to obtain a desired compound (1.53 kg). (2) 1-oxide 2, 3, 5-trimethyl-4-nitropyridine Formula 364 At 98% sulfuric acid (4.93 kg, 49.3 moles), 2, 3, 5-trimethylpyridine 1-oxide (1.38 kg, 10.1 moles) was added. Then 97% nitric acid was added dropwise (1.44 kg) to the same for 50 minutes, the mixture heated to 85 ° C for 4 hours. The reaction mixture was poured into a mixture of ammonium acid carbonate (10.6 kg) and water (9.0 L). The mixture was extracted with ethyl acetate (3.0 L x 3). The obtained organic layer was concentrated and dried under vacuum overnight to obtain a desired product (1.50 kg). (3) 4-chloro-2, 3, 5-trimethylpyridine 1-oxide Formula 365 To 2, 3, 5-trimethyl-4-nitropyridine 1-oxide (850 g, 4.67 mol), water (400 g) and 36% concentrated hydrochloric acid (1.69 kg) were added and the mixture was heated to 70 ° C. C. To the mixture, N, N-dimethylformamide (115 ml) was added and then the resulting mixture was heated to 100 ° C. After completion of the reaction, the reaction mixture was cooled to 20 ° C and emptied into a mixture of potassium carbonate (1.40 kg) and water (7 L). The mixture was extracted with chloroform (1.0 1 x 3), the organic layer was dried over sodium sulfate and concentrated. The crude product obtained was stirred for 2 hours in a mixture of diisopropyl ether (500 ml) and n-hexane (1.0 L), and then suction filtration was carried out. The obtained wet product was dried under vacuum overnight to obtain a desired product (666.4 g). (4) 1-oxide 4- (2,2-dimethyl-l, 3-dioxan-5-ylmethoxy) -2, 3, 5-trimethylpyridine Formula 366 A mixture of 1-oxide 4-chloro-2,3,5-trimethylpyridine (840 g), (2,2-dimethyl-l, 3-dioxan-5-yl) methanol (688 g) and toluene (2.52 L) it was heated under reflux while stirring the water content. While azeotropic dehydration continued, potassium hydroxide was added (0.58 kg) to the reaction mixture for 3 hours and 45 minutes, and azeotropic dehydration was continued for 2.5 hours. The mixture was cooled to 30 ° C or less, and ethyl acetate (2.5 L) and 17% saline (3.5 L) were added to the mixture and then the mixture was allowed to stand overnight. The ethyl acetate layer was separated and the aqueous layer was extracted with ethyl acetate (1.0 1 x 3). The ethyl acetate layers were combined, filtered through celite, and concentrated under reduced pressure to obtain a desired product (1.20 kg). (5) (4- (2,2-dimethyl-1,3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methanol monohydrate Formula 367 To a mixture of N-oxide 4- (2,2-dimethyl-1,3-dioxan-5-yl) methoxy-2,3,5-trimethylpyridine (1.20 kg) and sodium acetate (0.18 kg) heated to 50 ° C at 60 ° C, acetic anhydride (1.10 kg) was added dropwise during 1.5 hours. After 0.5 hours, the mixture was heated to 80 ° C for 4.5 hours and cooled to an internal temperature below 30 ° C or lower, allowed to stand, and concentrated under reduced pressure. The obtained residue was dissolved in methanol (1.0 L) and the solution was added to a mixture of 48% aqueous sodium hydroxide solution (0.71 kg) and cold water (2.85 L) for one hour. After stirring at room temperature for 5 hours and 45 minutes, the mixture was concentrated under reduced pressure. To the residue in this way concentrated, water (3.0 L) was added and the mixture was extracted with toluene (2.3 L x 4). The toluene layers were combined and washed with water (1.2 L). The obtained organic layer was filtered through celite and concentrated. To the residue obtained, diisopropyl ether (1.15 L) was added at room temperature and hot water (45 ° C, 74 ml) was also added. After confirming the precipitation of the crystal, the mixture was stirred at 25 ° C for one hour. After heptane (3.6 L) was drained, the mixture was stirred overnight. The mixture was further stirred under ice-cooling for 5 hours and then filtered to obtain a yellow crystal. To the yellow crystal obtained, diisopropyl ether (3.5 L) was added and the mixture was dissolved at 50 ° C. After the insoluble substance was removed by filtration, the mixture was gradually cooled and allowed to stand at 5 ° C overnight. The crystal obtained was filtered and washed with heptane (0.5 L) and dried with air to obtain a desired product (0.69 kg). (6) 2- (((4- (2,2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 368 A (4- (2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methanol monohydrate (690 g), toluene was added to carry out azeotropic dehydration (2.1 L x 5, 1.75 L x 1). To the obtained concentrated product, toluene (393 ml) was added to obtain a toluene solution (921 g) of (4- (2,2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin. -2-il) methanol. To the toluene solution of (4- (2, 2-dimethyl-l, 3- dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methanol (845.7 g, content: 61.7%, amount: 521.8 g, 1855 mol), tetrahydrofuran (2609 ml), toluene (669 ml) was added sequentially ) and triethylamine (375.3 g, 3,709 moles) in a nitrogen atmosphere. The mixture was stirred while cooling with ice / dry ethanol. After 30 minutes of initiating cooling, mentansulfonyl chloride (254.9 g, 2226 moles) was added dropwise for 42 minutes. After the completion of the dropwise addition, the mixture was stirred under cooling by an ice bath. After about 1.5 hours, a solution of tetrahydrofuran (3653 ml) of 2-mercaptobenzimidazole (334.28 g) was emptied., 2226 m) was added to the mixture for 2 minutes and the mixture was stirred at room temperature for approximately 18 hours. Toluene (3653 ml) and a 20% w / w aqueous sodium hydroxide solution (1852.4 g) were added to the reaction mixture and H20 (2322 ml) was further added. In this way, extraction and separation were performed. The organic layer was washed twice with a 20% w / w aqueous solution of ammonium chloride (4174 g) and further washed with H20 (4174 ml). The obtained organic layer was concentrated under reduced pressure (40 ° C) to obtain a brown oily substance (2.40 kg, containing toluene 1446 ml, tetrahydrofuran 168 ml, calculated from the Xl NMR spectrum). The brown oil thus obtained was transferred to a crystallization container, washed with toluene (119 ml), and the mixture was stirred at room temperature. After 10 minutes, tert-butyl methyl ester (134 ml) was emptied and the mixture was stirred continuously at room temperature. After 20 minutes, tert-butyl methyl ether (127 ml) was further added and the mixture was stirred continuously at room temperature. After 30 minutes, additional tert-butyl methyl ether (266 ml) was added per drop for 20 minutes, and the mixture was stirred continuously at room temperature. After a minute, the addition of tert-butyl methyl ether was also initiated (522 ml) by drip. After 8 minutes, the precipitation of the crystal was confirmed. The drip addition was finished in one hour and 20 minutes. After the resulting mixture was stirred at room temperature for 40 minutes, heptane (2348 ml) was added dropwise for one hour and 17 minutes and the mixture was stirred at room temperature overnight. Approximately after 15.5 hours of the heptane dropwise addition, the crystal precipitate was subjected to suction filtration, rinsed with toluene / tert-butyl methyl ether / heptane (587 ml / 391 ml / 587 ml) and dried with empty. The wet crystal thus obtained was dried with air (50 ° C) to obtain a desired product. Yield: 619.0 g, content: 96.5%, quantity: 597.3 g, yield: 77.8% (base amount), HPLC purity: 98.0% < HPLC Analysis Conditions (verification of Reaction, Measurement and Quantification of HPLC Purity) > Column: IMC-Pack Pro C18 AS-302 (5 μm, 150 mm × 4.6 mm D.D.) Eluent: solution A (MeCN / 20 mM AcONH4 ac = 100/900 (v / v)), solution B ( MeCN / 20 mM AcONH4 ac = 800/200 (v / v)) Flow rate: 1.0 ml / min Detection: UV 254 nm Oven temperature: 25 ° C sample temperature: 25 ° C Gradient condition (time / solution B conc.): 0. 01 min / 0% - > 25 min / 100% - > 30 min / 100% - > 30.01 min / 0% - > 40 min / stop TR = 18.4 min (7) Crude sodium salt of an optical isomer (Short in retention time) of 2- (((4- (2,2-dimethyl-l, 3-dioxan-5-yl ) methoxy-3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole Formula 369 The water content of 2- (((4- (2,2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole, toluene, L- (+) - diethyl tartrate, and N, N-diisopropylethylamine used in the reaction was measured using the Karl Fischer technique (total amount: 0.885 g). 2- (((4- (2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole (580.3 g, content: 96.5% , amount: 560.0 g, 1354 moles), toluene (3864 ml), and H20 (2.81 g, 0.156 moles) were added sequentially under a nitrogen atmosphere and the mixture was stirred with heating at 60 ° C. After 6 minutes, L- (+) - tartrate diethyl (122.9 g, 0.596 moles) with toluene (560 ml) was added to the resulting suspension, and the reagent bottle was washed. After 30 minutes, the solution was confirmed. After 8 minutes, titanium (IV) tetraisopropoxide (77.0 g, 0.271 mol) was added and the reagent bottle was washed with toluene (56 ml). The resulting mixture was stirred with heating at the same temperature for about one hour. The mixture was cooled to 8 ° C and N, N-diisopropylethylamine was added with toluene (280 ml) (56.01 g, 0.742 mole), and then, the reagent bottle was washed. After 10 minutes, a solution of toluene (840 ml) of eumeno hydroperoxide (259.2 g, 1422 mol) was added dropwise for 47 minutes and the mixture was stirred at 8 ° C for approximately 18.5 hours. An aqueous 30% w / w aqueous sodium thiosulfate solution (2240 g) was emptied and the mixture was stirred for 12 minutes, and then the aqueous layer was discarded. To the organic layer, a solution of 4% w / w aqueous sodium hydroxide (2240 g) was emptied and the mixture was stirred, and He let himself rest. The aqueous layer was separated to obtain an aqueous solution of an optical isomer (short in retention time) of 2- (((4- (2,2-dimethyl-l, 3-dioxan-5-yl) methoxy-3, 5-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole extracted with the aqueous solution of sodium hydroxide as a brown-yellow suspension. To toluene (7840 ml), the solution (2.98 kg) of an optical isomer (short in retention time) of 2 - (((4- (2, 2-dimethyl-1,3-dioxan-5-yl) methoxy-3,5-dimethylpyridine) -2-yl) methyl) sulfinyl) -benzimidazole extracted with the aqueous sodium hydroxide solution was emptied and the mixture was stirred. To the mixture, a solution of 20% aqueous acetic acid w / w (400 ml), an aqueous solution of 8% NaOH (50 ml), and a 20% aqueous acetic acid solution w / w were sequentially added. (8 ml) with stirring and the pH was adjusted to 8.64. The mixture was allowed to stand and separated, and the aqueous layer was discarded. The organic layer was washed with 5% aqueous w / w saline solution (2240 g), separated to obtain a toluene extraction solution of an optical isomer (short in retention time) of 2- (((4- ( 2, 2-dimethyl-1,3-dioxan-5-yl) methoxy-3, 3-dimethylpyridin-2-yl) methyl) sulfinyl) -benzimidazole (7.31 kg) (content: 567.7 g, 1322 moles) as a yellow-coffee solution. To the obtained toluene extraction solution, a solution of 28.3% methanol of sodium methoxide (245.6 g, 1.286 moles) was added for one minute with stirring to a room temperature. Subsequently, tert-butyl methyl ether (1120 ml) was added dropwise to this solution for 3 minutes, and the mixture was stirred at room temperature. After 6 minutes, it was confirmed that the crystal was precipitated. The mixture was stirred continuously for approximately 30 minutes. In addition, more tert-butyl methyl ether (7840 ml) was added dropwise for 2 hours and 40 minutes and continuously stirred at room temperature overnight. About 13 hours after adding tert-butylmethyl ether dropwise, the precipitated crystal was subjected to suction filtration, rinsed with toluene / tert-butyl methyl ether (1047 ml / 1193 ml) and dried with vacuum for 15 minutes.

The wet glass thus obtained was dried under reduced pressure (40 ° C) to obtain a desired product. Yield: 546.8 g, content: 101.7%, amount: 546.8 g (depending on the content was estimated as 100%), yield: 90.9% (base amount), HPLC purity: 98.2%, enantiomeric excess: 100% ee < HPLC Analysis Conditions (reaction verification, HPLC Purity Measurement and Quantification) > Column: IMC-Pack Pro C18 AS-302 (5 μm, 150 mm × 4.6 mm ID) Eluent: solution A (MeCN / 20 mM AcONH4 aq = 100/900 (v / v)), solution B (MeCN / 20 mM AcONH4 ac = 800/200 (v / v)) Flow rate: 1.0 ml / min Detection: UV 254 nm Oven temperature: 25 ° C Sample temperature: 25 ° C Gradient condition (time / conc. Solution B): 0.01 min / 0% - > 25 min / 100% - > 30 min / 100% - > 30.01 min / 0% - > 40 min / stop TR = 14.1 min < Conditions HPLC analysis (enantiomeric excess) > Column: DAICEL CHIRALPAK IA (250mm x 4.6 mm I.D.) Eluent: EtOH / MTBE = 150/850 (v / v) Flow rate: 1.0 ml / min Detection: UV 284 nm Oven temperature: 25 ° C Sample temperature: 25 ° C (8) Purified sodium salt of an isomer Optical (Short in retention time) of 2- (((4- (2,2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methyl) sulfinyl) - benzimidazole Formula 370 To a crude optical isomer (short in retention time) of 2- (((4- (2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy-3,5-dimethylpyridin-2-yl) methyl sodium sulfinyl) -benzimidazole (536.8 g, 1189 moles), ethanol (1074 ml) was added. The crude isomer was dissolved in ethanol at room temperature. To the solution, ter-butyl methyl ether (1074 ml) was also emptied. The solution thus obtained was subjected to suction filtration through a bed of Hiflo Super-Cel (107.4 g, washed sequentially with ethanol / tert-butyl methyl ether (1074 ml / 1074 ml) and tert-butyl methyl ether (537 ml )), and rinsed with ethanol / tert-butyl methyl ether (215 ml / 215 ml). The obtained filtrate was transferred to the crystallization container and washed with ethanol / tert-butyl methyl ether (54 ml / 54 ml) by complete transfer and start stirring at room temperature. Then, tert-butyl methyl ether (1610 ml) was added dropwise over 6 minutes and the mixture was stirred continuously at room temperature. After 11 minutes, tert-butyl methyl ether (268 ml) was added dropwise for 2 minutes and the mixture was stirred continuously. After one minute, the precipitation of the crystal was confirmed. The mixture was stirred continuously for 31 minutes and tert-butyl methyl ether (268 ml) was added dropwise for 9 minutes. After the mixture was stirred at room temperature for 8 minutes, in addition tert-butyl methyl ether (8589 ml) was added dropwise for one hour and 10 minutes and the mixture was stirred continuously at room temperature. About 22 hours after the drip addition of tert-butyl methyl ether was completed, the crystal The precipitate was subjected to filtration by suction while nitrogen was sprayed, washed sequentially with ethanol / tert-butylmethyl ether (107 ml / 966 ml), and tert-butyl methyl ether (1074 ml), and dried under vacuum for 8 minutes. From the obtained wet crystal (584.54 g), the wet glass (531.10 g) was dried under reduced pressure (50 ° C) to obtain a desired product. Yield: 419.6 g, HPLC purity: 99.4% <HPLC analysis conditions (HPLC purity measurement and quantification) > Column: IMC-Pack Pro C18 AS-302 (5 μm, 150mm x 4.6 mm I D.) Eluent: solution A (MeCN / 20 mM AcONH4 ac = 100/900 (v / v)), solution B (MeCN) / 20 mM AcONH4 ac = 800/200 (v / v)) Flow rate: 1.0 ml / min Detection: UV 254 nm Oven temperature: 25 ° C Sample temperature: 25 ° C Gradient condition (time / conc. solution B): 0.01 min / 0% - > 25 min. / 100% - > 30 min / 100% - > 30.01 min / 0% - > 40 min / stop TR = 14.1 min Production Example 1 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 371 (the) (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methylisulfonate Formula 372 It was dissolved (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methanol (2.5 g, 8.35 mmol as the water content estimated as 7.28%) in toluene and the mixture was subjected twice to azeotropic dehydration. The residue was dissolved in tetrahydrofuran (30 ml). To the solution, triethylamine (2.33 ml, 16.7 moles) was added and the mixture was stirred under a nitrogen atmosphere under cooling with ice. In addition, methanesulfonyl chloride (0.766 ml, 10 mmol) was added by dripping at an internal temperature below 11.5 ° C for 2 minutes. The reaction mixture was stirred for 13 minutes under the same Conditions were diluted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution. The organic layer was dried over magnesium sulfate and filtered through silica gel and the filtrate was concentrated under reduced pressure to obtain the title compound (2.8 g, 93.3%) as a light orange solid. X H NMR (400 MHz, DMSO-d 6) d PPM; 1.33 (3H, s), 1.37 (3H, s), 2.07-2.15 (lH, m), 2.23 (3H, s), 2.26 (3H, s), 3.22 (3H, s), 3.81 (2H, dd, J = 6, 12 Hz), 3.89 (2H, d, J = 7 Hz), 4.02 (2H, dd, J = 4, 12 Hz), 5.29 (2H, s), 8.24 (1H, s). (lb) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 373 To a mixture of (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl methanesulfonate (500 mg, 1.39 = mmoles), 2-mercaptobenzimidazole (209 mg, 1.39 mmol) and tetrahydrofuran (5 ml), triethylamine was added (0.387 ml, 2.78 mmol) and the mixture was stirred at room temperature for 14 hours and 25 minutes. The reaction mixture is concentrated under reduced pressure, and toluene and 0.1N of aqueous sodium hydroxide solution were added to the residue and the insoluble substance was removed by filtration. The organic layer was removed and the aqueous layer was extracted again with toluene. The organic layers were combined, washed with a saturated saline solution, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in n-heptane / ethyl acetate (1/1) and subjected to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = l / l-> 0 / l) to obtain the title compound (549 mg, 95.5%) as a colorless viscous oil. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.05-2.16 (lH,), 2.20 (3H, s), 2.28 (3H, s), 3.80 (2H, dd, J = 6, 12 Hz), 3.86 (2H, d, J = 7 Hz), 4.01 (2H, dd, J = 4, 12 Hz), 4.68 (2H, s), 7.08-7.14 (2H, m), 7.38-7.50 (2H, m) , 8.17 (1H, s). Production Example 2 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 374 (2a) 4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl-4-methylbenzenesulfonate Formula 375 To a solution of tetrahydrofuran (30 ml) of (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl-methanol (738 mg, 2.61 mmol) , powdered sodium hydroxide (313 mg, 7.84 mmol) was added and the mixture was stirred at room temperature for 35 minutes.The mixture was further stirred for 10 minutes under ice cooling and p-toluenesulfonyl chloride (1.09 g) was added. 5.74 mmol) was added slowly over one minute.The reaction mixture was stirred at room temperature for 17 hours and 40 minutes and diluted with tetrahydrofuran, then the insoluble substance was removed by filtration. , and the mixture was concentrated, and subjected to column chromatography on silica gel (elution solvent: n-heptane / acetate of ethyl = l / l) to obtain the title compound (1.00 g, 88%) as a white solid. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1. 37 (3H, s), 2.03-2.11 (HH, m), 2.07 (3H, s), 2.18 (3H, s), 2.41 (3H, s), 3.76-3.81 (4H, m), 4.00 (2H, dd, J = 4, 12 Hz), . 13 (2H, s), 7.42 (2H, d, J = 8 Hz), 7.73 (2H, d, J = 8 Hz), 8. 14 (1H, s). (2b) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 376 To a mixture of (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl-4-methylbenzenesulfonate (457 mg, 1.05 mmol) , 2-mercaptobenzimidazole (158 mg, 1.05 mmol), and tetrahydrofuran (5 ml), triethylamine (0.293 ml, 2.1 mmol) was added and the mixture was stirred at room temperature for 15 hours and 30 minutes. To the reaction mixture was added toluene and a dilute aqueous solution of sodium hydroxide and the organic layer was removed. The aqueous layer was extracted again with toluene. The organic layers were combined and washed with a saturated saline solution, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in n-heptane / ethyl acetate (1/1) and subjected to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = l / l-> 0 / l) to obtain the title compound (419 mg, 96.5%) as a colorless viscous oil. - H NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1. 36 (3H, s), 2.05-2.16 (lH, m), 2.20 (3H, s), 2.28 (3H, s), 3. 80 (2H, dd, J = 6, 12 Hz), 3.86 (2H, d, J = 7 Hz), 4.01 (2H, dd, J = 4, 12 Hz), 4.68 (2H, s), 7.08-7.14 (2H, m), 7.38-7.50 (2H, m), 8. 17 (1H, s) Production Example 3 2- (((4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 377 (3a) 2- (Chloromethyl) - (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridine Formula 378 To a solution of toluene (16 ml) of (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methanol (800 mg, 2.85 g) mmoles), triethylamine (0.397 ml, 2.85 mmol) was added and the mixture was stirred under a nitrogen atmosphere under cooling with ice. Thionyl chloride (0.208 ml, 2.85 mmol) was added per drop for 2 minutes at an internal temperature below 7.7 ° C and the mixture was stirred at room temperature for 20 minutes. The reaction mixture was diluted with ethyl acetate under cooling with ice and washed with a saturated aqueous solution of sodium hydrogen carbonate and a saline solution. The organic layer was dried over sodium sulfate, and filtered with silica gel. The filtrate was concentrated under reduced pressure to obtain the title compound (0.837 g, 98%) as a light brown oil substance. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1.37 (3H, s), 2.05-2.16 (lH, m), 2.21 (3H, s), 2.28 (3H, s), 3.8K2H, dd, J = 6, 12 Hz), 3.88 (2H, d, J = 7 Hz), 4.01 (2H, dd, J = 4, 12 Hz), 4.76 (2H, s), 8.19 (1H, s). (3b) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 379 To a mixture of 2- (chloromethyl) - (4- ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridine (837 mg, 2.79 mmol), 2-mercaptobenzimidazole (419 mg, 2.79 mmol) and sodium hydroxide (223 mg, 5.58 mmol), methanol (20 ml) was added and the mixture was stirred at room temperature for 12 hours and 55 minutes.The reaction mixture was concentrated under reduced pressure. Toluene and 0. IN of aqueous sodium hydroxide solution were added to the residue and the insoluble substance was removed by filtration, and then the organic layer was removed.The aqueous layer was extracted again with toluene.The organic layers were combined and washed with a saturated saline solution, dried over sodium sulfate, and filtered.The filtrate was concentrated under reduced pressure.The residue was dissolved in n-heptane / ethyl acetate (1/1) and subjected to chromatography. of column in silica gel (solvent elution: n-heptane / ethyl acetate = l / l-> 0 / l) to obtain the title compound it (980 mg, 84.9%) as a white foam. Xl NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1. 36 (3H, s), 2.05-2.16 (lH, m), 2.20 (3H, s), 2.28 (3H, s), 3.81 (2H, dd, J = 6, 12 Hz), 3.86 (2H, d, J = 7 Hz), 4.01 (2H, dd, J = 4, 12 Hz), 4.68 (2H, s), 7.08-7.14 (2H, m), 7.38-7.50 (2H, m), 8.17 (1H, s ). Production Example 4 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 380 (4a) (4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl acetate Formula 381 1- (2,2-Dimethyl-1,3-dioxan-5-yl) methoxy) -2,3,5-trimethylpyridine-1-oxide (10.5 g, 37.4 mmol) was dissolved in acetic anhydride (100 ml) and the solution was stirred at 85 ° C for 1.5 hours. After the reaction mixture was concentrated, the residue was purified by silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = l / l-> 0 / l) and a desired fraction was concentrated to obtain the title compound (6.1 g, 50.4%) as a light yellow solid. * H NMR (400 MHz, DMSO-d6) d PPM; 1.31 (3H, s), 1.35 (3H, s), 2.04 (3H, s), 2.05-2.13 (ÍH, m), 2.17 (3H, s), 2.19 (3H, s), 3.79 (2H, dd, J = 6, 12 Hz), 3.85 (2H, d, J = 7 Hz), 4.00 (2H, dd, J = 4, 12 Hz), 5.09 (2H, s), 8.17 (1H, s). (4b) 2- (((4- ((2,2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) thio) -benzimidazole Formula 382 To a solution of dimethyl sulfoxide (10 ml) of potassium t-butoxide (262 mg, 2.33 mmol) and 2-mercaptobenzimidazole (349 mg, 2.33 mmol), (4- ((2,2-dimethyl-1,3) was added. methyl-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) acetate (500 mg, 1.55 mmol) and the mixture was stirred under a nitrogen atmosphere at 150 ° C for 3 hours and 10 minutes . After it was cooled to room temperature, the mixture The reaction mixture was diluted with toluene and washed with a dilute aqueous sodium hydroxide solution and a saturated saline solution, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The residue was subjected twice to silica gel column chromatography (elution solvent: n-heptane / ethyl acetate = 1 / L) to obtain the title compound (441 mg, 68.8%) as a white foam. H NMR (400 MHz, DMSO-d6) d PPM; 1.33 (3H, s), 1.36 (3H, s), 2.05-2.16 (lH, m), 2.20 (3H, s), 2.28 (3H, s), 3.80 (2H, dd, J = 6, 12 Hz) , 3.86 (2H, d, J = 7 Hz), 4.01 (2H, dd, J = 4, 12 Hz), 4.68 (2H, s), 7.08-7.14 (2H, m), 7.38-7.50 (2H, m ), 8.17 (ÍH, s). Experimental Example 1 Inhibitory Effect of Gastric Acid Secretion in a Dog Having a Chronic Gastric Fistula (1) Method The compounds according to the Examples were investigated for an inhibitory effect against the secretion and persistence of gastric acid through the use of Large dogs (body weight: approximately 14 to 19 kg) with chronic gastric fistula. An experiment was carried out for 2 days. On the first day, histamine (50 or 75 μg / kg / h) was administered intravenously continuously for 3 hours. During the administration of histamine, the gastric juice was collected every 20 minutes. One hour after the initiation of the administration of histamine, a test compound (which is a compound prepared in the Examples) was administered suspended or dissolved in a 0.5% methylcellulose solution at a volume of 0.1 ml / kg through a catheter that moves inside the duodenum. The inhibitory effect of the test compound against the secretion of gastric acid was verified during the 2 hours after the administration. On the second day (ie, 24 hours after administration of the test compound), the histamine was administered intravenously continuously for two hours. During the administration of histamine, the gastric juice was collected every 20 minutes and the persistence of the inhibitory effect against the secretion of gastric acid was verified. After the amount of gastric juice was measured, I titrated a sample of 0.5 ml of gastric juice at a pH of 7.0 with a sodium hydroxide solution of 0.04 moles / one. In this way, the concentration of gastric juice was measured. The output of gastric acid (amount of secretion) was calculated by multiplying the volume of gastric juice by the concentration of acid. The inhibitory effect against the secretion of gastric acid was evaluated based on the inhibitory degree (%) of gastric acid secretion on the first day. The inhibitory effect (%) against the secretion of gastric acid was obtained according to the following equation. When the number of animals was two or more, an average value was obtained. The inhibitory effect against gastric acid secretion (%) = (AB) / A x 100 [A]: Gastric acid output (amount of secretion) for 20 minutes 40 minutes after the start of histamine administration at one hour after. [B]: the gastric acid outlet for 20 minutes one hour and 40 minutes after administration of the test compound two hours later. The persistence of the inhibitory effect against the secretion of gastric acid was evaluated based on the inhibitory degree (%) against the gastric acid secretion on the second day. The persistence (%) of the inhibitory effect against the secretion of gastric acid was obtained according to the following equation: The persistence (%) of the inhibitory effect against gastric acid secretion = (CD) / C x 100 [C]: Amount total output of gastric acid from the start of the administration of histamine (on the first day to one hour later). [D]: Total amount of gastric acid output from the start of histamine administration (on the second day to one hour later). (2) Results Table 1 Preparation Example 1 Capsule 30.0 g of sodium salt of (2 - (((4- ((2, 2-dimethyl-l, 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2 was dissolved. -yl) methyl) sulfinyl) -benzimidazole then referred to as "Compound A"), 8.1 g of ethyl cellulose (trade name: Etcel, manufactured by Dow Chemical Co.) and 16.2 g of hydroxypropyl cellulose (trade name: HPC-L, manufactured by Shin-Etsu Chemical Co. Ltd.) at 489 g of dehydrated ethanol. This solution was applied to 500.1 g of a core substance, Nonpareil 108 (trade name, manufactured by Freund Corporation) through the use of the granule machine for coating the fluid bed of the Wurster type (trade name: Multiplex, Pawlek) and dried to obtain granules. Then, 48.6 g of ethylcellulose (trade name: Etcel, Dow Chemical Co.) and 291.9 g of hydroxypropylcellulose (trade name: HPC-L, Shin-Etsu Chemical Co. Ltd.) were dissolved in dehydrated ethanol (6860 g). Further 136.8 g of magnesium stearate (manufactured by Marin Klot) was dispersed in this solution to prepare a coating solution. The granules (554.4 g) prepared above were covered with the coating solution and dried to prepare coated granules of the intermediate layer. In addition 460.2 g of hydroxypropylmethyl cellulose phthalate (trade name: HP-55S, ShinEtsu Chemical Co. Ltd.) and 45.3 g of diacetylated monoglyceride (trade name: Mibassett, manufactured by Quest International) were dissolved in an 80% aqueous solution of ethanol (11045 g). In addition, 42.3 g of talc (trade name: Talc, manufactured by Matsumura Industry) and 24.3 g of titanium oxide (trade name: Titanium (IV) oxide, manufactured by Merck) were dispersed in the ethanol solution obtained above. The coated granules of the intermediate layer (1031.7 g) were covered with the dispersion solution and dried to obtain enteric-coated granules. To enteric-coated granules (1603.8 g), 15.0 g of light anhydrous silicic acid (trade name: AEROSIL-200 (Japanese Pharmacopoeia), manufactured by Nippon Aerosil), and 15.0 g of talc (trade name, Hi-filler) were added. # 17, manufactured by Matsumura Industry) and mixed through the use of a container-type mixer (trade name: 2/5 L container type mixer, manufactured by Toyo Packing) to obtain Compound A, which was charged to capsules in an amount of 1 mg / capsule. Preparation Example 2 Capsule The granules were prepared according to the following recipe in the same manner as Preparation Example 1. Compound A was loaded into capsules in an amount of 10 mg / capsule.

Table 4 Unit: g Nonpareil 103 (Trade name, Freund Corporation) Industrial Applicability The compounds of the present invention greatly inhibit the secretion of gastric acidthey persistently inhibit the secretion of gastric acid, are safe, appropriately stable, and thus can conveniently be used as a medicament, especially therapeutic medicine or prophylactic drug for diseases or symptoms related to acid. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (41)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A compound represented by Formula 1 characterized in that R1 and R2 can be the same or different and each represents a hydrogen atom or a C1-C6 alkyl group; R2 is a group represented by Formula 2 wherein W2 represents a hydrogen atom, C1-C6 alkyl group or halogen atom (provided, the occurrence of W2 in a benzene ring may be from 1 to 3, and may be the same or different); nor represents 1 to 5; n2 represents 1 to 4; and n3 represents 1 to 6, the group optionally has from 1 to 4 groups selected from the group Al consisting of a halogen atom, C1-C6 alkyl group, C1-C6 alkoxy group, C1-C6 haloalkyl group, C1-C6 alkoxy group-C1-C6 alkyl and hydroxyl group; R4, R5, R6 and R may be the same or different and each represents a hydrogen atom, a hydroxyl group, a halogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, an alkoxy group of C1-C6, or haloalkoxy group of C1-C6, or a combination of R5 and R6 represent a methylenedioxy group or an ethylenedioxy group; and W1 represents a straight-chain or branched-chain alkylene group having one to eight carbon atoms, or a salt thereof, or a solvate thereof.
2. 2. The compound or a salt thereof, or a solvate thereof according to claim 1, characterized in that R1 is a hydrogen atom or a methyl group.
3. 3. The compound or a salt thereof, or a solvate thereof according to claim 1, characterized in that R1 is a methyl group.
4. 4. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 3, characterized in that R1 is a group represented by Formula 3 wherein represents a hydrogen atom, a C1-C6 alkyl group or a halogen atom (provided, the occurrence of 2 in the benzene ring may be from 1 to 3, and may be the same or different); ni represents 1 to 5, n2 represents 1 to 4; and n3 represents 1 to 6, the group optionally has 1 or 2 groups selected from group A2 consisting of a fluorine atom, a methyl group, an ethyl group, a propyl group, a methoxy group and a monofluoromethyl group.
5. 5. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 3, characterized in that R2 is a group represented by the formula (4): Formula 4
6. 6. The compound or a salt thereof, or a solvate of these according to any of claims 1 to 3, characterized in that R2 is a group represented by Formula 5
7. 7. The compound or a salt thereof, or a solvate thereof according to any one of claims 1 to 6, characterized in that R3 is a hydrogen atom or a methyl group.
8. 8. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 6, characterized in that R3 is a methyl group.
9. 9. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 8, characterized in that R4 is a hydrogen atom, a hydroxyl group, a methyl group, an ethyl group, a methoxy group , ethoxy group or fluorine atom.
10. 10. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 8, characterized in that R4 is a hydrogen atom, a methyl group or a fluorine atom.
11. 11. The compound or a salt thereof, or a solvate thereof according to any one of claims 1 to 8, characterized in that R4 is a hydrogen atom.
12. 12. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 11, characterized in that R5 is a hydrogen atom, a hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or fluorine atom.
13. 13. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 11, characterized in that R5 is a hydrogen atom, methyl group, or fluorine atom.
14. 14. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 11, characterized in that R5 is a hydrogen atom.
15. 15. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 14, characterized in that R6 is a hydrogen atom, a hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or fluorine atom.
16. 16. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 14, characterized in that R6 is a hydrogen atom, methyl group, or fluorine atom.
17. 17. The compound or a salt thereof, or a solvate of these according to any of claims 1 to 14, characterized in that R6 is a hydrogen atom.
18. 18 The compound or a salt thereof, or a solvate thereof according to any one of claims 1 to 17, characterized in that R7 is a hydrogen atom, a hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or atom of f lúor.
19. 19 The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 17, characterized in that R7 is a hydrogen atom, methyl group, or fluorine atom.
20. 20. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 17, characterized in that R7 is a hydrogen atom.
21. 21. The compound or a salt thereof, or a solvate thereof according to any one of claims 1 to 20, characterized in that 1 is an individual bond, methylene group, or ethylene group.
22. 22. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 20, characterized in that 1 is a methylene group. 2. 3 .
23. The compound or a salt thereof, or a solvate thereof according to any one of claims 1 to 4, characterized in that all occurrences of W2 are hydrogen atoms.
24. 24. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 4, characterized in that it is not from 1 to 3. The compound or a salt thereof, or a solvate thereof according to with any of claims 1 to 4, characterized in that neither is 1 or 2. 26. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 4, characterized in that n2 is 1 or 2. 27. The compound or a salt thereof, or a solvate thereof according to any of claims 1 to 4, characterized in that n3 is 1 to 4. 28. The compound or a salt thereof, or a solvate of these according to any of claims 1 to 4, characterized in that n3 is 1 or 2. 29. The compound or a salt thereof, or a solvate thereof according to claim 1, characterized in that it is one selected from the following group. consisting of 2- (((4- ((5, 5-dimethyl-l, 3-dioxan- 2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((3-methyl-4- (1,5,9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((-4 ((2,2-dimethyl-1,3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((3-methyl-4- (2- (8-methyl-l, 4,7,9-tetraoxaspiro [4.5] dec-8-yl) ethoxy) pyridin-2-yl) methyl) sulfinyl) 1 -H-benzimidazole; 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) pyridin-2-yl) ethyl) sulfinyl) -lH-benzimidazole; 2- (((4- (2- (8-ethyl-1,4,7,8-tetraoxaspiro [4.5] dec-8-yl) ethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1 H -benzimidazole; 2- (((4- (1, 3-dioxolan-4-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((4- ((2, 2-bis (fluoromethyl) -1,3-dioxan-5-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -1H-benzimidazole; 2- (((4- (5,9-dioxaspiro [3.5] non-7-yloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((4- ((2-methoxy-1,3-dioxan-5-yl) methyloxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 2- (((3-methyl-4- ((8-methyl-1,4,7,9-tetraoxaspiro [4.5] dec-8-yl) methoxy) pyridin-2-yl) methyl) sulfinyl) -lH- benzimidazole; 2- (((4- (5,9-dioxaspiro [3.5] non-7-ylmethoxy) iridin-2-yl) ethyl) sulfinyl-lH-benzimidazole, or 2- (((4- ((5, 5- difluoro-l, 3-dioxan-2-yl) methoxy) -3- methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole; 30. 2- (((4- ((5,5-dimethyl-1,3-dioxan-2-yl) methoxy) -3-methylpyridin-2-yl) methyl) sulf inyl) -lH-benzimidazole or a salt of the same, or solvate of these. 31. 2- (((4- (5,7-dioxaspiro [2.5] oct-6-ylmethoxy) -3-methylpyridin-2-yl) methyl) sulfinyl) -lH-benzimidazole or a salt thereof, or solvate of these. 32. 2- (((3-methyl-4- (1, 5, 9-trioxaspiro [5.5] undec-3-ylmethoxy) pyridin-2-yl) methyl) sulf inyl) -lH-benzimidazole or a salt thereof , or solvate of these. 33. 2- (((4- ((2,2-dimethyl-1,1- 3-dioxan-5-yl) methoxy) -3,5-dimethylpyridin-2-yl) methyl) sulf inyl) -lH-benzimidazole or a salt thereof, or solvate of these. 34. A medicament characterized in that it comprises the compound or a salt thereof, or a solvate thereof according to any one of claims 1 to 33. 35. An inhibitor for the secretion of gastric acid characterized in that it comprises the compound or a salt of the same, or a solvate thereof according to any one of claims 1 to 33. 36. A therapeutic agent or prophylactic agent for diseases or symptoms related to acid characterized in that it comprises the compound or a salt thereof, or a solvate thereof. according to any one of claims 1 to 33. 37. The therapeutic agent or prophylactic agent of according to claim 36, characterized in that the diseases or symptoms related to acid are gastric ulcer, duodenal ulcer, anastomotic ulcer, gastroesophageal reflux disease (including gastroesophageal reflux disease with relapses and repeated recurrences), Zollinger-Ellison syndrome, disease of symptomatic gastroesophageal reflux, endoscopically negative gastroesophageal reflux disease, non-erosive gastroesophageal reflux disease, gastroesophageal regurgitation, NUD (non-ulcer dyspepsia), abnormal sensation in the throat, Barrett's esophagus, ulcer induced by? SAID, gastritis, gastric bleeding , hemorrhagic gastritis, gastrointestinal bleeding, peptic ulcer, bleeding ulcer, tension ulcer, gastric hyperacidity, dyspepsia, gastroparesis, ulcer of elderly person, intractable ulcer, acute gastric mucosal lesion, heartburn, heartburn of sleep apnea syndrome , br uxism, gastralgia, heavy stomach sensation, vomiting, nausea, arthrosis of the temporomandibular joint, or erosive gastritis. 38. The therapeutic agent or prophylactic agent according to claim 36, characterized in that the diseases or symptoms related to acid are gastric ulcer, duodenal ulcer, anastomotic ulcer, gastroesophageal reflux disease, Zollinger-Ellison syndrome, symptomatic gastroesophageal reflux disease, endoscopically negative gastroesophageal reflux disease, non-erosive gastroesophageal reflux disease, or acute gastric mucosal lesion. 39. The therapeutic agent or prophylactic agent according to claim 36, characterized in that the diseases or symptoms related to acid are gastroesophageal reflux disease, or symptomatic gastroesophageal reflux disease. 40. The therapeutic agent or prophylactic agent according to claim 36, characterized in that the diseases or symptoms related to acid are gastric ulcer, or duodenal ulcer. 41. A bacterial agent or an antibacterial agent against Helicobacter pylori in the stomach, characterized in that it comprises the compound or salt thereof, or a solvate thereof according to any of claims 1 to 33.