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RU98110659A - METHOD FOR SYNTHESIS OF BENZIMIDAZOLE COMPOUNDS - Google Patents

METHOD FOR SYNTHESIS OF BENZIMIDAZOLE COMPOUNDS

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Publication number
RU98110659A
RU98110659A RU98110659/04A RU98110659A RU98110659A RU 98110659 A RU98110659 A RU 98110659A RU 98110659/04 A RU98110659/04 A RU 98110659/04A RU 98110659 A RU98110659 A RU 98110659A RU 98110659 A RU98110659 A RU 98110659A
Authority
RU
Russia
Prior art keywords
methoxy
pyridinyl
dimethyl
methyl
benzimidazole
Prior art date
Application number
RU98110659/04A
Other languages
Russian (ru)
Other versions
RU2166502C2 (en
Inventor
Андерс Густавссон
Оке Келлстрем
Original Assignee
Астра Актиеболаг
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from SE9504503A external-priority patent/SE521100C2/en
Application filed by Астра Актиеболаг filed Critical Астра Актиеболаг
Publication of RU98110659A publication Critical patent/RU98110659A/en
Application granted granted Critical
Publication of RU2166502C2 publication Critical patent/RU2166502C2/en

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Claims (14)

1. Способ производства 5-метокси-2-[[(4-метокси-3,5-диметил-2-пиридинил)-метил] сульфинил] -1H-бензимидазола из (4-метокси-3,5-диметил-2-пиридинил)метилового спирта, включающий следующие реакционные стадии
Стадия 1:
Figure 00000001

(4-Метокси-3,5-диметил-2-пиридинил)метиловый спирт (Пирметиловый спирт) + SOCl2 (или другой подходящий хлорирующий агент)
Figure 00000002

(4-Метокси-3,5-диметил-2-пиридинил)метилхлорид (Пирметилхлорид)
Стадия 2:
Figure 00000003

Figure 00000004

(4-Метокси-3,5-диметил-2-пиридинил)метилхлорид (Пирметилхлорид) + 2-Меркапто-5-метокси-бензимидазол (Метмерказол)
Figure 00000005

5-Метокси-2-(((4-метокси-3,5-диметил-2-пиридинил)-метил)-тио)-1Н-бензимидазол (Пирметазол)
Стадия 3:
Figure 00000006

5-Метокси-2(((4-метокси-3,5-диметил-2-пиридинил)-метил)-тио)-1Н-бензимидазол (Пирметазол) м-Хлорпероксибензойная кислота
Figure 00000007

5-Метокси-2(((4-метокси-3,5-диметил-2-пиридинил)-метил)сульфинил)-1Н-бензимидазол (Омепразол)
отличающийся тем, что реакционные стадии проводят последовательно без выделения промежуточных соединений, образующихся по ходу проведения способа, с использованием одной главной системы растворителей, общей для всей реакционной последовательности.1. Method for the production of 5-methoxy-2 - [[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -1H-benzimidazole from (4-methoxy-3,5-dimethyl-2- pyridinyl) methyl alcohol, comprising the following reaction steps
Stage 1:
Figure 00000001

(4-Methoxy-3,5-dimethyl-2-pyridinyl) methyl alcohol (Pymethyl alcohol) + SOCl 2 (or other suitable chlorinating agent)
Figure 00000002

(4-Methoxy-3,5-dimethyl-2-pyridinyl) methyl chloride (Pymethyl chloride)
Stage 2:
Figure 00000003

Figure 00000004

(4-Methoxy-3,5-dimethyl-2-pyridinyl) methyl chloride (Pyrmethyl chloride) + 2-Mercapto-5-methoxy-benzimidazole (Metmercazole)
Figure 00000005

5-Methoxy-2 - (((4-methoxy-3,5-dimethyl-2-pyridinyl) methyl) thio) -1H-benzimidazole (pyrmethazole)
Stage 3:
Figure 00000006

5-Methoxy-2 (((4-methoxy-3,5-dimethyl-2-pyridinyl) methyl) thio) -1H-benzimidazole (pyrimethazole) m-chloroperoxybenzoic acid
Figure 00000007

5-Methoxy-2 (((4-methoxy-3,5-dimethyl-2-pyridinyl) methyl) sulfinyl) -1H-benzimidazole (Omeprazole)
characterized in that the reaction stages are carried out sequentially without isolation of intermediate compounds formed during the process using one main solvent system common to the entire reaction sequence. 2. Способ по п.1, отличающийся тем, что система растворителей содержит главный растворитель и возможно один или более чем один сорастворитель. 2. The method according to claim 1, characterized in that the solvent system contains a main solvent and possibly one or more than one co-solvent. 3. Способ по п.2, отличающийся тем, что главный растворитель представляет собой метиленхлорид. 3. The method according to claim 2, characterized in that the main solvent is methylene chloride. 4. Способ по п.2, отличающийся тем, что главный растворитель представляет собой толуол. 4. The method according to claim 2, characterized in that the main solvent is toluene. 5. Способ по п.2, отличающийся тем, что сорастворителем является спирт. 5. The method according to claim 2, characterized in that the co-solvent is alcohol. 6. Способ по п.1, отличающийся тем, что стадию 1 проводят при температуре между -5oС и 25oС.6. The method according to claim 1, characterized in that stage 1 is carried out at a temperature between -5 o C and 25 o C. 7. Способ по п.1, отличающийся тем, что стадию 2 проводят с катализатором фазового переноса. 7. The method according to claim 1, characterized in that stage 2 is carried out with a phase transfer catalyst. 8. Способ по п.7, отличающийся тем, что катализатор фазового переноса представляет собой бромид тетрабутиламмония. 8. The method according to claim 7, characterized in that the phase transfer catalyst is tetrabutylammonium bromide. 9. Способ по п.1, отличающийся тем, что стадию 2 проводят при температуре 30 - 60oС.9. The method according to claim 1, characterized in that stage 2 is carried out at a temperature of 30-60 o C. 10. Способ по любому из пп.1 - 9, отличающийся тем, что полученный 5-метокси-2-[[(4-метокси-3,5-диметил-2-пиридинил)-метил] сульфинил] -1Н-бензимидазол далее очищают на стадии очистки. 10. The method according to any one of claims 1 to 9, characterized in that the obtained 5-methoxy-2 - [[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -1H-benzimidazole further cleaned at the stage of purification. 11. Способ по п.10, отличающийся тем, что стадия очистки включает в себя кристаллизацию из одного или нескольких органических растворителей. 11. The method according to claim 10, characterized in that the purification step includes crystallization from one or more organic solvents. 12. Способ по п.10, отличающийся тем, что стадия очистки включает в себя осаждение из щелочной воды путем снижения рН посредством добавления кислоты или алкилформиата. 12. The method according to claim 10, characterized in that the purification step involves precipitation from alkaline water by lowering the pH by adding an acid or an alkyl formate. 13. Фармацевтический препарат, содержащий 5-метокси-2-[[(4-метокси-3,5-диметил-2-пиридинил)-метил] сульфинил]-1Н-бензимидазол и фармацевтически приемлемый носитель или разбавитель, отличающийся тем, что 5-метокси-2-[[(4-метокси-3,5-диметил-2-пиридинил)-метил]сульфинил]-1Н-бензимидазол получен способом по одному из пп.1 - 12. 13. A pharmaceutical preparation containing 5-methoxy-2 - [[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -1H-benzimidazole and a pharmaceutically acceptable carrier or diluent, characterized in that 5 -methoxy-2 - [[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -1H-benzimidazole obtained by the method according to one of claims 1 to 12. 14. 5-Метокси-2-[[(4-метокси-3,5-диметил-2-пиридинил)-метил]сульфинил] -1Н-бензимидазол, полученный способом по одному из пп.1 - 12. 14. 5-Methoxy-2 - [[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -1H-benzimidazole obtained by the method according to one of claims 1 to 12.
RU98110659/04A 1995-12-15 1996-12-05 Method of synthesis of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl- 2-pyridinyl)- methyl]-sulfinyl]-1h-benzimidazole RU2166502C2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9504503A SE521100C2 (en) 1995-12-15 1995-12-15 Process for the preparation of a benzimidazole compound
SE9504503-5 1995-12-15

Publications (2)

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RU98110659A true RU98110659A (en) 2000-05-20
RU2166502C2 RU2166502C2 (en) 2001-05-10

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Country Status (39)

Country Link
US (1) US5958955A (en)
EP (1) EP0868423B1 (en)
JP (1) JP3523267B2 (en)
KR (1) KR100433436B1 (en)
CN (1) CN1113879C (en)
AR (1) AR004834A1 (en)
AT (1) ATE205201T1 (en)
AU (1) AU704422B2 (en)
CA (1) CA2238864C (en)
CO (1) CO4750654A1 (en)
CZ (1) CZ288661B6 (en)
DE (2) DE69615052T2 (en)
DK (1) DK0868423T3 (en)
DZ (1) DZ2137A1 (en)
EE (1) EE03768B1 (en)
EG (1) EG23859A (en)
ES (1) ES2125210T3 (en)
HR (1) HRP960581B1 (en)
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MX (1) MX9804603A (en)
MY (1) MY115661A (en)
NO (1) NO314306B1 (en)
NZ (1) NZ324482A (en)
PL (1) PL186132B1 (en)
PT (1) PT868423E (en)
RU (1) RU2166502C2 (en)
SE (1) SE521100C2 (en)
SI (1) SI0868423T1 (en)
SK (1) SK282347B6 (en)
TN (1) TNSN96148A1 (en)
TR (1) TR199801070T2 (en)
TW (1) TW460474B (en)
UA (1) UA62921C2 (en)
WO (1) WO1997022603A1 (en)
YU (1) YU49420B (en)
ZA (1) ZA9610067B (en)

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