138786-67-1

Basic information

• Product Name: 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium
• Synonyms: 5-(DIFLUOROMETHOXY)-2-[[(3,4-DIMETHOXY-2-PYRIDINYL)METHYL]SULFINYL]-1H-BENZIMIDAZOLE;5-(difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1h-benzimidazole sodium;EUPANTOL;PANTOPRAZOLE SODIUM;PANTOPRAZOLE, SODIUM SALT;PANTECTA;PANTOZOL;1h-benzimidazole,5-(difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sul
• CAS NO: 138786-67-1
• Molecular Formula: C₁₆H₁₄F₂N₃O₄S*Na
• Molecular Weight: 405.35
• EINECS: 1312995-182-4
• Product Categories: Active Pharmaceutical Ingredients;Antibiotic Explorer;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Pantoprazole;Aromatics;Heterocycles;Sulfur & Selenium Compounds
• Mol File: 138786-67-1.mol

Chemical Properties

• Melting Point: 199-202°C
• Boiling Point: 586.9oC at 760 mmHg
• Flash Point: 308.7oC
• Appearance: white to off-white solid
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly, Sonicated), Water (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium(138786-67-1)
• EPA Substance Registry System: 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium(138786-67-1)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-37/38-41-48
• Safety Statements: 22-26-36/37/39-45
• Hazardous Substances Data: 138786-67-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium is used as an antiulcerative and gastric pump inhibitor for treating conditions such as gastroesophageal reflux disease (GERD), erosive esophagitis, and Zollinger-Ellison syndrome. It works by blocking the final step of gastric acid production, providing relief from symptoms and promoting healing of the affected areas.
Used in Gastrointestinal Applications:
In the gastrointestinal field, 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium is utilized for its ability to reduce gastric acid secretion, which can help in the management of various gastrointestinal disorders, including peptic ulcers and gastroduodenal ulcers.
Brand Name:
The brand name for 5-(Difluoromethoxy)-2-(((3,4-dimethoxy-2-pyridinyl)methyl) sulfinyl)-1H-benzimidazole sodium is Protonix, which is manufactured by Wyeth.

Originator

Controloc,Byk Gulden ,Germany

Therapeutic Function

Antiulcer

InChI:InChI=1/C16H14F2N3O4S.Na/c1-23-13-5-6-19-12(14(13)24-2)8-26(22)16-20-10-4-3-9(25-15(17)18)7-11(10)21-16;/h3-7,15H,8H2,1-2H3;/q-1;+1/rC16H14F2N3NaO4S/c1-24-13-5-6-19-11(14(13)25-2)8-27(23)16-20-10-7-9(26-15(17)18)3-4-12(10)21(16)22/h3-7,15H,8H2,1-2H3

Synthetic route

5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (102625-70-7) → pantoprazole sodium (138786-67-1)

Conditions	Yield
With sodium hydroxide In water; acetonitrile at 20℃;	95%
With sodium hydroxide In ethanol for 5h; Reflux;	95%
With sodium hydroxide In water; ethyl acetate at 20℃; for 5.5h;	92%

pantoprazole sulfide (102625-64-9) → pantoprazole sodium (138786-67-1)

Conditions	Yield
Stage #1: pantoprazole sulfide With sodium hydroxide; tert-butylhypochlorite In dichloromethane; water at 0 - 5℃; for 1h; Stage #2: With sodium hydroxide In water; acetone at 0 - 25℃; for 7h;	95%
Stage #1: pantoprazole sulfide With potassium tungstate dihydrate; dihydrogen peroxide at -5 - 0℃; for 4.5h; pH=3.5; Stage #2: With sodium hydroxide In water at 20℃; Temperature; Reagent/catalyst;	78.7%
With sodium hypochlorite; sodium hydroxide In methanol; water at -20 - -5℃;
Stage #1: pantoprazole sulfide With sodium hypochlorite; sodium hydroxide In water; acetonitrile at -5 - 30℃; Stage #2: With acetic acid In dichloromethane at 25 - 30℃; pH=8 - 8.5; Stage #3: With sodium hydroxide In dichloromethane; water at 25 - 30℃; Concentration;
Stage #1: pantoprazole sulfide With sodium hypochlorite; water; sodium hydroxide In ethyl acetate at 0 - 10℃; for 7h; Stage #2: With sodium thiosulfate In ethyl acetate for 0.333333h;

5-(difluoromethoxy)-2-mercapto-1H-benzimidazole (97963-62-7) + 2-Chloromethyl-3,4-dimethoxy-pyridine; hydrochloride (72830-09-2) → pantoprazole sodium (138786-67-1)

Conditions	Yield
Stage #1: 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole; 2-Chloromethyl-3,4-dimethoxy-pyridine; hydrochloride With sodium hydroxide; tetrabutylammomium bromide In dichloromethane; water at 25 - 30℃; for 12h; Stage #2: With sodium hydroxide; sodium hypochlorite In dichloromethane; water at 0 - 8℃; for 6h; Product distribution / selectivity;	83%

2-hydroxymethyl-3,4-dimethoxypyridine hydrochloride + 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole (97963-62-7) → pantoprazole sodium (138786-67-1)

Conditions

Yield

Stage #1: 2-hydroxymethyl-3,4-dimethoxypyridine hydrochloride With thionyl chloride In dichloromethane at 0 - 15℃; for 1h; Stage #2: 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole With sodium hydroxide; tetrabutylammomium bromide In dichloromethane; water at 10 - 30℃; for 12h; pH=10 - 11; Stage #3: With sodium hydroxide; sodium hypochlorite In dichloromethane; water at 0 - 8℃; for 6h; Product distribution / selectivity;

79.6%

(5-difluoromethoxy)-2-[(4-chloro-3-methoxy-2-pyridinyl)methyl]thio-1H-benzimidazole (368890-20-4) + sodium methylate (124-41-4) → pantoprazole sodium (138786-67-1)

Conditions	Yield
In methanol at 50℃; Heating / reflux;	70.8%

5-(difluoromethoxy)-2-[[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (409098-86-8) → pantoprazole sodium (138786-67-1)

Conditions	Yield
With sodium methylate In methanol at 50℃; Heating / reflux;	70.8%

pantoprazole sulfide (102625-64-9) → 5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl-1-oxide)methylsulfonyl]-1H-benzoimidazole + pantoprazole sodium (138786-67-1) + Pantoprazole sulfone

Conditions	Yield
With sodium hydroxide; sodium hypochlorite In water; ethyl acetate at -5℃; for 1 - 1.5h; Product distribution / selectivity;	A n/a B 65% C n/a

5-(difluoromethoxy)-2-mercapto-1H-benzimidazole (97963-62-7) → pantoprazole sodium (138786-67-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 8 h / 80 °C 2: 3-chloro-benzenecarboperoxoic acid / chloroform / 4 h / 0 °C 3: sodium hydroxide / ethanol / 5 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / water; methanol / 3.5 h / 40 - 55 °C 2: LACTIC ACID; peracetic acid / methanol; dichloromethane / 1 h / -25 - -20 °C 3: sodium hydroxide / water; acetone / 40 - 45 °C View Scheme

sodium hydroxide (1310-73-2) + 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (102625-70-7) → pantoprazole sodium (138786-67-1)

Conditions	Yield
In water; acetonitrile at 25 - 35℃; for 1h;
In ethanol; dichloromethane; water at 20℃; pH=12.5; Product distribution / selectivity;

2-chloromethyl-3,4-dimethoxypyridine hydrochloride + 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole (97963-62-7) → pantoprazole sodium (138786-67-1)

Conditions	Yield
Stage #1: 2-chloromethyl-3,4-dimethoxypyridine hydrochloride; 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole With sodium hydroxide In ethanol; water at 35℃; for 2h; Stage #2: With sodium borate In ethanol at 45℃; for 2h; Stage #3: With dihydrogen peroxide In water at 20℃; for 2.5h; Concentration; Temperature;	19.61 g

pantoprazole sodium (138786-67-1) → zinc (S)-bis{[5-(difluoromethoxy)]-2-[(3,4-dimethoxy-2-pyridinyl)-methylsulphinyl]-1H-benzimidazolide}

Conditions	Yield
With zinc(II) chloride In water at 20℃; for 1.5h;	95%

pantoprazole sodium (138786-67-1) → magnesium {[5-(difluoromethoxy)]-2-[(3,4-dimethoxy-2-pyridinyl)methylsulphinyl]-1H-benzimidazolide} hydroxy

Conditions	Yield
Stage #1: pantoprazole sodium With sodium hydroxide In water at 25℃; for 1h; Stage #2: With magnesium chloride In water at 25℃; for 1h;	94.6%

pantoprazole sodium (138786-67-1) + zinc(II) chloride (7646-85-7) → zinc {[5-(difluoromethoxy)]-2-[(3,4-dimethoxy-2-pyridinyl)methylsulphinyl]-1H-benzimidazolide} hydroxy

Conditions	Yield
Stage #1: pantoprazole sodium With sodium hydroxide In water at 25℃; for 1h; Stage #2: zinc(II) chloride In water at 25℃; for 20h;	94.2%

(S)-1,1,2-triphenyl-1,2-ethanediol (108998-83-0) + pantoprazole sodium (138786-67-1) → C20H18O2*C16H15F2N3O4S

Conditions	Yield
With acetic acid In ethanol for 0.5h; pH=7 - 8; Reflux; Industrial scale;	94%

pantoprazole sodium (138786-67-1) → pantoprazole sodium sesquihydrate

Conditions	Yield
With water In tert-butyl methyl ether at 20 - 30℃; for 12h; Product distribution / selectivity;	92.4%
With water In di-isopropyl ether at 20 - 30℃; for 1 - 12h; Product distribution / selectivity;	91.93%
With water In diethyl ether at 20 - 30℃; for 12h; Product distribution / selectivity;	91.93%
With water at 0 - 35℃; Product distribution / selectivity;	91.4%
With water In dichloromethane at 25 - 35℃; for 1.5h; Product distribution / selectivity;

pantoprazole sodium (138786-67-1) → clcium {[5-(difluoromethoxy)]-2-[(3,4-dimethoxy-2-pyridinyl)methylsulphinyl]-1H-benzimidazolide} hydroxy

Conditions	Yield
Stage #1: pantoprazole sodium With sodium hydroxide In water at 25℃; for 1h; Stage #2: With calcium chloride In water at 25℃; for 20h;	91.8%

pantoprazole sodium (138786-67-1) → calcium bis{[5-(difluoromethoxy)]-2-[(3,4-dimethoxy-2-pyridinyl)-methylsulphinyl]-1H-benzimidazolide}

Conditions	Yield
With calcium chloride In water at 20℃; for 1.91667h;	73%

pantoprazole sodium (138786-67-1) → magnesium {[5-(difluoromethoxy)]-2-[(3,4-dimethoxy-2-pyridinyl)methylsulphinyl]-1H-benzimidazolide} hydroxy

Conditions	Yield
Stage #1: pantoprazole sodium With sodium hydroxide In water at 25℃; for 0.25h; Stage #2: With magnesium chloride In water at 25℃; for 2.5h;	52.7%

pantoprazole sodium (138786-67-1) → magnesium bis[5-[difluoromethoxy]-2-[[3,4-dimethoxy-2-pyridinyl]-methylsulfinyl]-1H-benzimidazolide]

Conditions	Yield
With magnesium chloride In water at 20 - 30℃; for 21 - 22h;

pantoprazole sodium (138786-67-1) → pantoprazole sodium

Conditions	Yield
With sodium hydroxide In ethanol for 24h; Heating / reflux;
In tert-butyl methyl ether; acetonitrile at 20℃; for 48h;
at 100℃;

3-chlorosulfonylbenzoic acid 2-(toluene-4-sulfonyl)ethyl ester (651728-72-2) + pantoprazole sodium (138786-67-1) → 3-[5-difluoromethoxy-2-{(3,4-dimethoxy-pyridin-2-yl)-methanesulfinyl}-benzimidazole-1-sulfonyl]benzoic acid 2-(toluene-4-sulfonyl)ethyl ester + 3-[6-difluoromethoxy-2-{(3,4-dimethoxy-pyridin-2-yl)-methanesulfinyl}-benzimidazole-1-sulfonyl]benzoic acid 2-(toluene-4-sulfonyl)ethyl ester (651728-78-8)

Conditions	Yield
With sodium hydrogencarbonate; triethylamine In dichloromethane at 20℃; for 1.5h;

(4-chlorosulfonylphenoxy)acetic acid 2-(toluene-4-sulfonyl)ethyl ester (651728-13-1) + pantoprazole sodium (138786-67-1) → 4-[5-difluoromethoxy-2-{(3,4-dimethoxypyridin-2-yl)methanesulfinyl}benzimidazole-1-sulfonyl]phenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester + 4-[6-difluoromethoxy-2-{(3,4-dimethoxypyridin-2-yl)methanesulfinyl}benzimidazole-1-sulfonyl]phenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester (651728-69-7)

Conditions	Yield
With sodium hydrogencarbonate; triethylamine In dichloromethane
With sodium hydrogencarbonate; triethylamine In dichloromethane Inert atmosphere;

pantoprazole sodium (138786-67-1) → 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-chloromethyl]sulfinyl]-1H-benzimidazole (812664-93-0) + 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)chlorohydroxymethyl]sulfinyl]-1H-benzimidazole (812664-94-1)

Conditions	Yield
With sodium hydroxide; sodium hypochlorite In water; acetonitrile at 20℃; for 12h;

pantoprazole sodium (138786-67-1) → 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole (102625-70-7)

Conditions	Yield
Stage #1: pantoprazole sodium With ethanol Stage #2: With water

pantoprazole sodium (138786-67-1) → 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole sodium salt monohydrate (797789-88-9)

Conditions	Yield
In acetone Purification / work up; Heating / reflux;
With water In ethyl acetate; acetone at 0 - 55℃; for 2.25h; Product distribution / selectivity;
With water In ethyl acetate at 0 - 5℃; for 2h; Product distribution / selectivity;

pantoprazole sodium (138786-67-1) → pantoprazole sodium sesquihydrate

Conditions	Yield
With water In ethyl acetate; acetone at 0 - 55℃; for 2.25h; Product distribution / selectivity;
With water In ethyl acetate at 0 - 5℃; for 2h; Product distribution / selectivity;

(4-chlorosulfonylphenoxy)acetic acid 2-(toluene-4-sulfonyl)ethyl ester (651728-13-1) + pantoprazole sodium (138786-67-1) → 4-[6-difluoromethoxy-2-{(3,4-dimethoxypyridin-2-yl)methanesulfinyl}benzimidazole-1-sulfonyl]phenoxyacetic acid sodium salt + 4-[5-difluoromethoxy-2-{(3,4-dimethoxypyridin-2-yl)methanesulfinyl}benzimidazole-1-sulfonyl]phenoxyacetic acid sodium salt

Conditions	Yield
Stage #1: (4-chlorosulfonylphenoxy)acetic acid 2-(toluene-4-sulfonyl)ethyl ester; pantoprazole sodium With sodium hydrogencarbonate; triethylamine In dichloromethane Inert atmosphere; Stage #2: With water; sodium hydrogencarbonate In acetonitrile at 65℃; for 5h; Inert atmosphere;

pantoprazole sodium (138786-67-1) + β‐cyclodextrin (7585-39-9) → C16H14F2N3O4S(1-)*C42H70O35*Na(1+)

Conditions	Yield
In water

Upstream product

• 368890-20-4 (5-difluoromethoxy)-2-[(4-chloro-3-methoxy-2-pyridinyl)methyl]thio-1H-benzimidazole 
• 124-41-4 sodium methylate 
• 409098-86-8 5-(difluoromethoxy)-2-[[(4-chloro-3-methoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole 
• 97963-62-7 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole 
• 72830-09-2 2-Chloromethyl-3,4-dimethoxy-pyridine; hydrochloride 
• 102625-64-9 pantoprazole sulfide 
• 1310-73-2 sodium hydroxide 
• 102625-70-7 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole 

Downstream Products

• 651728-78-8 3-[6-difluoromethoxy-2-{(3,4-dimethoxy-pyridin-2-yl)-methanesulfinyl}-benzimidazole-1-sulfonyl]benzoic acid 2-(toluene-4-sulfonyl)ethyl ester 
• 651728-69-7 4-[6-difluoromethoxy-2-{(3,4-dimethoxypyridin-2-yl)methanesulfinyl}benzimidazole-1-sulfonyl]phenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester 
• 102625-70-7 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole 
• 812664-93-0 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-chloromethyl]sulfinyl]-1H-benzimidazole 
• 812664-94-1 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)chlorohydroxymethyl]sulfinyl]-1H-benzimidazole 

Relevant articles and documents

Synthetic method and application of pantoprazole sodium

The invention belongs to the field of medicine synthesis, and discloses a synthesis method and application of pantoprazole sodium. The pantoprazole sodium is synthesized by the following steps: firstly carrying out sulfinylation on 5-difluoromethoxy-2-sulfenyl-1H-benzimidazole, and then carrying out Suzuki reaction on the 5-difluoromethoxy-2-sulfenyl-1H-benzimidazole and ((3, 4-dimethoxypyridine-2-yl) methyl) boric acid. According to the invention, the synthesis method of pantoprazole sodium provided by the invention can effectively improve the utilization rate of raw materials, improve the yield of intermediates and further reduce the production cost; the purification process of the synthesized intermediate and the final product in the synthesis method is simple, and the technological process is further shortened; and the synthesis method provided by the invention is suitable for synthesizing pantoprazole sodium, and the synthesized pantoprazole sodium is used for preparing a pantoprazole sodium injection.

Preparation method of pantoprazole sodium sesquihydrate single crystal form

The invention belongs to the technical field of chemical pharmacy, and relates to a preparation method of a pantoprazole sodium sesquihydrate single crystal form. The preparation method comprises thefollowing steps: (1) adding pantoprazole sodium monohydrate and a solvent into a reaction kettle, and heating to dissolve the pantoprazole sodium monohydrate in the solvent; (2) heating the solution in the reaction kettle to 60-65 DEG C, adding pantoprazole sodium sesquihydrate seed crystals, and separating out a pantoprazole sodium sesquihydrate crystal under stirring through programmed heating and cooling; and (3) centrifuging and drying the separated pantoprazole sodium sesquihydrate crystal. The preparation method of the pantoprazole sodium sesquihydrate single crystal form is simple to operate, low in cost, suitable for large-scale production and high in crystal form purity and is used for preparing the pantoprazole sodium sesquihydrate single crystal form.

Preparation of Pantoprazole sodium method and Pantoprazole sodium (by machine translation)

The invention relates to the preparation of Pantoprazole sodium method and pantoprazole sodium. In particular, the invention relates to a method of preparing pantoprazole sodium, comprising the following steps: 1) to 2 - hydroxymethyl - 3, 4 - dimethoxy pyridine (II) as the starting material, in under the action of chloride, the compound of formula III; 2) will be of the formula III compound in the presence of an inorganic base with 5 - difluoro - 2 - mercapto - 1 H - benzimidazole condensation, the compound of formula IV; 3) will be of the formula IV compound is oxidized by an oxidant generating 5 - difluoro - 2 - [(3, 4 - dimethoxy - 2 - pyridyl) methyl] sulfinyl - 1 H - benzimidazole is pantoprazole; 4) the obtained 5 - difluoro - 2 - [(3, 4 - dimethoxy - 2 - pyridyl) methyl] sulfinyl - 1 H - benzimidazole with sodium hydroxide reaction to produce salt that pantoprazole sodium (I); and optionally a 5) the resulting pantoprazole sodium is refined. The method of the invention said product has high purity, and the related impurities such as oxidation impurity, reducing the impurity, decomposition low impurity content. (by machine translation)

A pantoprazole sodium production process (by machine translation)

Pantoprazole sodium (Pantoprazole Sodium), chemical name 5 - difluoro - 2 - [[ (3, 4 - dimethoxy - 2 - pyridyl) - methyl] sulfinyl] - 1 H - benzimidazole sodium monohydrate, is the treatment of peptic ulcer and acute gastric mucosal lesion caused by bleeding of a safe, effective drug, to peptic ulcer and reflux esophagitis have very high cure rate. For the injection of the injection by the German hectogram (Byk Gulden) the pharmaceutical Company (now renamed Takeda pharmaceutical companies) lead to the successful development of, for 1994 years 10 months in south Africa listed for the first time, tradenames for pan tuo lOOc. The present invention provides a pantoprazole sodium production process. A specific process comprises the following process: 1, pantoprazole sodium intermediate synthesis of IV; 2, pantoprazole sodium crude synthesis of V; 3, crude refined product. (by machine translation)

Method for refining pantoprazole sodium

The invention discloses a method for refining pantoprazole sodium. The method comprises the following steps: suspending a crude product of pantoprazole sodium in an ethanol-water mixed solution, adjusting the pH value to be 7.0-8.0 by using 1mol/L of hydrochloric acid, washing, and drying so as to obtain pantoprazole; dissolving pantoprazole into a mixed liquid of methanol and dichloromethane, dropping a sodium hydroxide-water solution, filtering a crystal, washing, and drying in vacuum, so as to obtain medicinal-grade pantoprazole sodium. The method is simple and convenient to operate, low inrefining cost and applicable to industrial amplification operation, and the prepared pantoprazole sodium is high in yield, high in purity, low in solvent residue, good in color and good in stability.

Method for preparing high-purity razole intermediate and medicine by using green technology instead of phosgene, thionyl chloride and other toxic and harmful substances

The invention discloses a method for preparing a high-purity razole intermediate and a medicine by using a green technology instead of phosgene, thionyl chloride and other toxic and harmful substances. The preparation method comprises the following steps: dissolving Ph3PO in an organic solvent, placing the obtained solution in a reaction bottle, dropwise adding BTC to form a high-efficiency chloration reagent, carrying out a heat insulation reaction for a period of time after the dropwise addition is finished, dissolving a razole hydroxide in the organic solvent, dropwise adding the obtained solution to the above system, carrying out a heat insulation reaction for a period of time, carrying out suction filtration, and drying the obtained dried reaction product to obtain razole chloride. In the process, the Ph3PO is equivalently regenerated, a mother liquor part is concentrated to precipitate the Ph3PO at a low temperature, and the Ph3PO can be repeatedly used after being washed with a solvent with small polarity. The method has the advantages of few side reactions, high product quality, few "three wastes" pollutions, high atomic economy, and good promotion and application prospect. The invention also provides a relevant razole medicine prepared from the razole chloride obtained through the green technology. The medicine has obviously higher purity than medicines obtained through traditional methods.

A process for the preparation of Pantoprazole sodium

The invention belongs to the technical field of medicines and particularly relates to a preparation method of pantoprazole sodium. Aiming at operation of condensation, oxidization and salification by adopting a one-pot process in the prior art, a phase transfer catalyst is added into the condensation process, so that the reaction speed and yield are increased. By virtue of catalytic oxidation of hydrogen peroxide in the presence of tungstate, the selectivity of the reaction is improved and the impurities are reduced. The method provided by the invention is simple to operate, the yield and the purity of the product are improved, and the method is suitable for industrial production.

A adopt the particle process crystal product molecular assembly and shape optimization technique preparation of Pantoprazole sodium compound and its preparation (by machine translation)

The invention discloses a method for the preparation of pantoprazole sodium compound, the compound is [...] particle process crystal product molecular assembly and shape optimization technique to prepare. The compound as anhydrous pantoprazole sodium, has high purity, low hygroscopicity, the impurity content is low, good stability characteristics. At the same time, the invention also discloses a kind of Pantoprazole sodium pharmaceutical composition, said pharmaceutical composition comprising the following components by weight: pantoprazole sodium (to [...] ) 40-80 parts, metal ion complexing agent 0.05-0.1 parts and pH regulator proper amount. (by machine translation)

PROCESS FOR THE PREPARATION OF 2-PYRIDINYLMETHYLSULFINYL BENZIMIDAZOLES, THEIR ANALOGS AND OPTICALLY ACTIVE ENANTIOMERS

The present invention provides a commercially viable, cost effective and energy efficient process for the preparation of 2-pyridinylmethylsulfinyl benzimidazoles, their analogs and optically active enantiomers or pharmaceutically acceptable salts, hydrates or solvates thereof in high purity via application of reactors such as plug flow reactor, microreactor, microfluidic flow reactor, tubular flow reactor, coil-type flow reactor, laminar flow reactor, packed bed reactor, fluidized bed reactor or fixed bed reactor.

PROCESS FOR THE PREPARATION OF PANTOPRAZOLE SODIUM AND PANTOPRAZOLE SODIUM SESQUIHYDRATE

The present invention relates to a process for the preparation of pantoprazol sodium sesquihydrate of formula (I) and pantoprazole sodium.