cas 86604-78-6, 3,5-Dimethyl-4-methoxy-2-pyridinemethanol

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Preparation method of omeprazole intermediate
The invention relates to a preparation method of an omeprazole intermediate. According to the method, Nmethoxy-4-methoxy3, 5-dimethyl pyridinium is used as a raw material, metal ions are added as an additive, under the action of persulfate, 2-hydroxymethyl- 3, 5-dimethyl -4methoxypyridine is efficiently prepared, and then the 2-hydroxymethyl -3, 5-dimethyl- 4-methoxypyridine is further converted into 2-chloromethyl -3, 5-dimethyl- 4methoxypyridine hydrochloride. According to the method, the conversion rate, the yield and the quality of the 2-hydroxymethyl- 3, 5-dimethyl -4-methoxy pyridine areremarkably improved, so that the purity of the 2-chloromethyl- 3, 5-dimethyl- 4-methoxy pyridine hydrochloride obtained by further reaction is improved, the impurity content is reduced, the product yield and the production efficiency can be effectively improved, the production capacity is improved, and the production cost is reduced.
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Paragraph 0063-0065; 0067-0069; 0071-0073; 0075-0077; 0079

(2021/01/15)

Preparation method of omeprazole impurity
The invention relates to a preparation method of an omeprazole impurity I. Specifically, in the existence of KI, compound III and compound VII can react under the action of alkali to obtain a compound I, and after related aftertreatment, the impurity reference substance I meeting the quality requirements can be obtained.
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Paragraph 0013; 0017; 0021

(2017/12/27)

Slow, spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets: Isolation and structural characterization of the toxic antioxidants 3H-benzimidazole-2-thiones
The spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets upon long-term and forced storage conditions was determined by high performance liquid chromatography (HPLC). The more abundant products could be isolated by liquid chromatography and their molecular weights determined by Mass Spectrometry (MS). Their structures, established according to their spectroscopic data, were compared to those of either the literature or of authentic samples. Thus lansoprazole led mainly to a mixture of 3H-benzimidazole-2-thione (2a) and 3H-benzimidazole-2-one (2c), omeprazole mainly to a mixture of 5-methoxy-3H-benzimidazole-2-thione (1a) and 2-hydroxymethyl-3, 5-dimethyl- 4-methoxypyridine (1b), and pantoprazole, to 5-difluoromethoxy-3H-benzimidazole-2-thione (3a) and 2-hydroxymethyl-3, 4-dimethoxypyridine (3b). Although some of the degradation products had already been observed under different conditions, the detection of benzimidazole-2- thiones is unprecedented and their involvement as possible physiological, yet toxic antioxidants must be emphasized. Plausible, unified mechanisms for the formation of the different degradation products observed herein and in previous papers from the literature are suggested.
Rajab,Touma,Rudler,Afonso,Seuleiman
p. 749 - 754
(2013/10/08)

Synthesis of pharmaceutically useful pyridine derivatives
A process is provided for the preparation of compounds of formula I, useful in the preparation of compounds such as Omeprazole, Lansoprazole and Pantoprazole, wherein R1=H or CH3, R2=H or CH3, R3=Alkoxy (1-4C), OCH2CF3, Cyano, Hydrogen, Halogen, Acetoxy or Aryloxy, any electron withdrawing group or salts (organic or inorganic) of electron donating groups, R=Alkoxy, Hydroxy, Halogen, Activated ester, Tosylate, Mesylate, Thiol or Xanthyl, wherein the process for the preparation of compound of formula I employs a free radical reaction to functionalize the 2-position.
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(2008/06/13)

Syntheses of 2-[(3,5-dimethyl-4-methoxypyridyl)alkyl]-benzothiazolidine derivatives as a potential gastric H+/K+-ATPase inhibitor
A series of 2-[(3,5-dimethyl-4-methoxypyridyl)alkyl]benzothiazolidine derivatives were synthesized and tested their inhibitory effects on gastric H+/K+-ATPase. Compound 4d exhibited potent in vitro inhibitory activity.
Yoon, Sung-Hwa,Seo, SeungKi,Lee, YoungHee,Hwang, SungKwan,Kim, Dong Yeon
p. 1909 - 1912
(2007/10/03)

Structure-activity relationship of 2-[[(2-Pyridyl)methyl]thio]-1H- benzimidazoles as anti Helicobacter pylori agents in vitro and evaluation of their in vivo efficacy
A relationship between the structure of 21 2-[[(2-pyridyl)methyl]thio]- 1H-benzimidazoles (6) and their anti Helicobacter pylori activity expressed as minimum bactericidal concentration (MBC) values is described. Observed MBCs ranged from 256 to 1 μg/mL. The structure - activity relationship (SAR) showed that larger and more lipophilic compounds, especially compounds with such substituents in the 4-position of the pyridyl moiety, generally had lower MBC values. Four new compounds 'that were predicted to be potent by the established SAR model were synthesized and tested. One such compound, i.e., 2-[[(4-[(cyclopropylmethyl)oxy]3-methyl-2-pyridyl)methyl]thio]-1H- benzimidazole (18), was tested for in vivo efficacy in a mouse Helicobacter felis model (125 μmol/kg bid given orally for 4 days, n = 4). Unfortunately, antibacterial activity could not be clearly demonstrated in this model. Instead a potent acid secretion inhibition was observed. This finding was attributed to the methylthio compound being oxidized to the corresponding methyl sulfinyl derivative, i.e., a proton pump inhibitor, in vivo. Although the antibacterial activity had the potential of decreasing H. felis cell counts in vivo the proton pump inhibitory effect became dominant and actually promoted H. felis cell growth. Hence, we conclude that the antibacterial utility of the 2-[[(2-pyridyl)methyl]thio]1H-benzimidazoles (6) as a compound class is compromised by their propensity to become proton pump inhibitors upon metabolic oxidation in vivo.
Kühler, Thomas C.,Swanson, Marianne,Shcherbuchin, Vladimir,Larsson, H?kan,Mellg?rd, Bj?rn,Sj?str?m, Jan-Eric
p. 1777 - 1788
(2007/10/03)

Synthesis of 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine : A key intermediate for omeprazole
A synthesis of 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine, a key intermediate for the preparation of gastric acid inhibiting compound omeprazole, is described. The procedure consists of preparation of pyrone, pyridone and pyridine derivatives sequentially.
Chou, Shan-Yen,Chen, Shyh-Fong
p. 77 - 85
(2007/10/03)

1,3,4-oxadiazoles
1,3,4-oxadiazole compounds are disclosed. The subject compounds suppress immune function and have hepatoprotection activity.
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(2008/06/13)

Process of preparing 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine
A process of preparing 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine including the steps of acylating 2-methyl-1-penten-1-alkoxy-3-one to obtain 2-alkoxycarbonyl-3,5-dimethyl-4-pyrone; ammonolyzing 2-alkoxycarbonyl-3,5-dimethyl-4-pyrone to obtain 2-alkoxycarbonyl-3,5-dimethyl-4(1H)-pyridone; halogenating 2-alkoxycarbonyl-3,5-dimethyl-4(1H)-pyridone to obtain 2-alkoxycarbonyl-4-halo-3,5-dimethylpyridine; methoxylating 2-alkoxycarbonyl-4-halo-3,5-dimethylpyridine to obtain 2-methoxycarbonyl-3,5-dimethyl-4-methoxypyridine; and reducing 2-methoxycarbonyl-3,5-dimethyl-4-methoxypyridine to obtain 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine.
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(2008/06/13)

Process for the preparation of 2-halomethyl-3,5-dimethyl-4-methoxypyridine halohydrate
The process comprises a first step of O-acylation and subsequent acyloxylation of the 2-position methyl group of 2,3,5-trimethyl-4-methoxypyridine N-oxide, to obtain a compound which is subjected to a final halogenation step, in which the 2-position substituent is converted into halomethyl with a halogenating agent.
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(2008/06/13)

(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate
[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.
Kohl,Sturm,Senn-Bilfinger,Simon,Kruger,Schaefer,Rainer,Figala,Klemm
p. 1049 - 1057
(2007/10/02)

2--1H-thienoimidazoles. A Novel Class of Gastric H+/K+-ATPase Inhibitors
2-thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K+-ATPase.The isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo.Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thienoimidazole lead to highly active compounds with a favorable chemical stability.Various substitution patterns in the thienoimidazole moiety result in lower biological activity.The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation.Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K+-ATPase blocker introduced on the market.
Weidmann, Klaus,Herling, Andreas W.,Lang, Hans-Jochen,Scheunemann, Karl-Heinz,Rippel, Robert,et al.
p. 438 - 450
(2007/10/02)

3,5-dimethyl-4-methoxypyridine derivatives
A process for the preparation of compounds of formula I STR1 in which X is the radical OH or Cl, by the catalytic hydrogenation of 3,5-dimethyl-4-methoxy-2-cyanopyridine, subsequent reaction of the resulting 3,5-dimethyl-4-methoxy-2-aminomethylpyridine to give 3,5-dimethyl-4-methoxy-2-hydroxymethylpyridine and, if desired, chlorination to give 3,5-dimethyl-4-methoxy-2-chloromethylpyridine, and the novel intermediate 3,5-dimethyl-4-methoxy-2-aminomethylpyridine.
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(2008/06/13)

(Bezimidazol-2-yl)-pyridinium compounds
(Benzimidazol-2-yl)-pyridinium compounds of the formula STR1 wherein A is --SR9, --SO3- or --S--SO3- ; R1 and R3 each is hydrogen or (C1 -C7)-alkyl; R2 is hydrogen, (C1 -C7)-alkyl, (C1 -C7)-alkoxy or a negatively charged oxygen atom; R4 is hydrogen or a negative charge; R5, R6, R7 and R8 each is hydrogen, (C1 -C7)-alkyl, aryl, halogen, cyano, nitro, formyl, (C2 -C7)-alkanoyl, arylcarbonyl, carboxy, carboxy-(C1 -C7)-alkyl, (C1 -C7)-alkoxycarbonyl, aryloxycarbonyl, aryl-(C1 -C7)-alkoxycarbonyl, (C1 -C7)-alkoxycarbonyl-(C1 -C7)-alkyl, carbamoyl, mono- or di-(C1 -C7)-alkylcarbamoyl, pyrrolidinocarbonyl, piperidinocarbonyl, carbamoyl-(C1 -C7)-alkyl, mono- or di-(C1 -C7)-alkylcarbamoyl-(C1 -C7)-alkyl, pyrrolidinocarbonyl-(C1 -C7)-alkyl, piperdinocarbonyl-(C1 -C7)-alkyl, hydroxy, (C1 -C7)-alkoxy, (C2 -C7)-alkanoloxy, aryloxy, arylcarbonyloxy, (C1 -C7)-alkoxycarbonyloxy, aryl-(C1 -C7)-alkoxycarbonyloxy, aryloxycarbonyloxy, carbamoyloxy, mono- or di-(C1 -C7)-alkylcarbamoyloxy, pyrrolidinocarbonyloxy, piperidinocarbonyloxy, hydroxy-(C1 -C7)-alkyl, trifluoromethyl, di-(C1 -C7)-alkoxymethyl or (C2 -C3)-alkylenedioxymethyl or two of these substituents which are adjacent jointly and together with the carbon atoms to which they are attached are a 5-, 6- or 7-membered ring; and R9 is (C1 -C20)-alkyl, (C3 -C7)-cycloalkyl, (C3 -C7)-alkenylalkyl, (C3 -C7)-alkynylalkyl, substituted (C3 -C7)- alkenyl-alkyl, aryl, aryl-(C1 -C7)-alkyl, hydroxy- (C2 -C7)-alkyl, (C1 -C7)-alkoxy- (C2 -C7)-alkyl, (C1 -C7)-alkoxycarbonyl- (C1 -C7)-alkyl, carboxy-(C1 -C7)-alkyl, di-(C1 -C7)-alkoxycarbonyl-(C2 -C7)-alkyl, dicarboxy-(C2 -C7)-alkyl, carboxy-(C1 -C7)-alkylcarbamoyl-(C1 -C7)-alkyl, optionally N-substituted amino-(C2 -C7)-alkyl, optionally N-substituted amino-carboxy-(C2 -C7)-alkyl, optionally N-substituted amino-(C1 -C7)-alkoxycarbonyl-(C2 -C7)-alkyl, heteroaryl, heteroaryl-(C1 -C7)-alkyl or a residue derived from a cysteine-containing oligopeptide by elimination of the SH group; provided that when there is a net single positive charge there is an external anion, or a pharmaceutically acceptable acid addition salt thereof.
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(2008/06/13)

Tricyclic imidazole derivatives
Tricyclic imidazole derivatives of formula I STR1 wherein one of R1 and R3 is lower alkyl and the other is hydrogen or lower alkyl, R2 is lower alkyl, n is the number 0 or 1, A is STR2 R4, R5, R6 and R7 each is lower alkyl and R8 is hydrogen or lower alkyl, and their acid addition salts are described. These compounds are useful as agents for control or prevention of ulcers and of increased gastric acid secretion.
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(2008/06/13)

Certain pyridyl-N-oxide intermediates for the preparation of omeprazole
Novel compounds of the formula STR1 wherein R is H or CH3, a process for their preparation, and their use as intermediates in the preparation of pharmaceutically useful compounds, e.g. substituted benzimidazoles containing a pyridine radical, i.a. omeprazole.
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(2008/06/13)

Fluoroalkoxy substituted benzimidazoles useful as gastric acid secretion inhibitors
Fluoroalkoxy compounds of the general formula I STR1 wherein R1 represents a 1-3C-alkyl radical which is completely or predominantly substituted by fluorine, or a chlorodifluoromethyl radical, R1' represents hydrogen, halogen, trifluoromethyl, a 1-3C-alkyl radical, or a 1-3C-alkoxy radical which is optionally completely or predominantly substituted by fluorine, R2 represents hydrogen or a 1-3C-alkyl radical, R3 represents hydrogen or a 1-3C-alkyl or 1-3C-alkoxy radical, R4 represents hydrogen or a 1-3C-alkyl radical and n represents the number 0 or 1, and their salts are new compounds with a marked protective effect on the stomach.
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(2008/06/13)