CA2471730A1 - Process for preparing and purifying 1,7'-dimethyl-2'-propyl-2,5'-bi-1h-benzimidazole - Google Patents
Process for preparing and purifying 1,7'-dimethyl-2'-propyl-2,5'-bi-1h-benzimidazole Download PDFInfo
- Publication number
- CA2471730A1 CA2471730A1 CA002471730A CA2471730A CA2471730A1 CA 2471730 A1 CA2471730 A1 CA 2471730A1 CA 002471730 A CA002471730 A CA 002471730A CA 2471730 A CA2471730 A CA 2471730A CA 2471730 A1 CA2471730 A1 CA 2471730A1
- Authority
- CA
- Canada
- Prior art keywords
- process according
- propyl
- benzimidazole
- charcoal
- methyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- ILXRSCZVHSZGCS-UHFFFAOYSA-N 4-methyl-6-(1-methylbenzimidazol-2-yl)-2-propyl-1h-benzimidazole Chemical compound C1=CC=C2N(C)C(C3=CC(C)=C4N=C(NC4=C3)CCC)=NC2=C1 ILXRSCZVHSZGCS-UHFFFAOYSA-N 0.000 title claims abstract 5
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 14
- 239000003610 charcoal Substances 0.000 claims 7
- XWAJTVCEILFDGU-UHFFFAOYSA-N 7-methyl-2-propyl-3h-benzimidazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2NC(CCC)=NC2=C1C XWAJTVCEILFDGU-UHFFFAOYSA-N 0.000 claims 3
- 239000011541 reaction mixture Substances 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- RPKCLSMBVQLWIN-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1N RPKCLSMBVQLWIN-UHFFFAOYSA-N 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- 238000005119 centrifugation Methods 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 238000002425 crystallisation Methods 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- 238000000746 purification Methods 0.000 claims 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims 2
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 239000008346 aqueous phase Substances 0.000 claims 1
- 239000012043 crude product Substances 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 238000010979 pH adjustment Methods 0.000 claims 1
- 229960005187 telmisartan Drugs 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a process which can be used on an industrial scale for preparing and purifying 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole.
Claims (13)
1. Process for purifying 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole which has been prepared by reacting 2-propyl-4-methyl-1H-benzimidazole-6-carboxylic acid or the salts thereof with N-methyl-o-phenylene-diamine or the salts thereof, characterised in that the crude product is treated with charcoal.
2. Process according to claim 1, characterised in that 2-propyl-4-methyl-1H-benzimidazole-6-carboxylic acid is reacted with N-methyl-o-phenylene-diamine or the salts thereof in the presence of methanesulphonic acid and phosphorus pentoxide.
3. Process according to claim 1 or 2, characterised in that the reaction is carried out at a temperature of 125 to 145°C.
4. Process according to one of claims 1 to 3, characterised in that after the end of the reaction, hydrolysis and pH adjustment, the reaction mixture is added to the charcoal or charcoal is added to the reaction mixture.
5. Process according to claim 4, characterised in that the charcoal treatment is carried out at a temperature of 70 to 80°C.
6. Process according to claim 4 or 5, characterised in that the charcoal treatment is carried out at a pH of 0.7 to 1.2.
7. Process according to one of claims 4 to 6, characterised in that the quantity of charcoal used is from 5 to 20 percent by weight of the 2-propyl-4-methyl-1H-benzimidazole-6-carboxylic acid used.
8. Process according to one of claims 4 to 7, characterised in that the purification step is repeated one to three times after the filtration or centrifugation of the reaction mixture.
9. Process according to one of claims 4 to 8, characterised in that after the purification by treatment with charcoal, the following steps are carried out in succession:
a) an organic solvent is added, b) a base is added to obtain a pH of 5 to 6, c) the aqueous phase is separated off, d) the 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole is isolated from the organic phase by crystallisation and subsequent filtration or centrifugation.
a) an organic solvent is added, b) a base is added to obtain a pH of 5 to 6, c) the aqueous phase is separated off, d) the 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole is isolated from the organic phase by crystallisation and subsequent filtration or centrifugation.
10. Process according to claim 9, characterised in that isopropanol is used as the organic solvent in step a).
11. Process according to one of claims 9-10, characterised in that in step b), the base is added at a temperature of 70 to 80°C.
12. Process according to one of claims 9 to 11, characterised in that in step d), the crystallisation is carried out by the addition of water.
13. Use of the 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole obtained by a process according to one of claims 1-12 for preparing telmisartan.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10201725.5 | 2002-01-18 | ||
| DE10201725A DE10201725A1 (en) | 2002-01-18 | 2002-01-18 | Process for the preparation and purification of 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole |
| PCT/EP2003/000319 WO2003059890A1 (en) | 2002-01-18 | 2003-01-15 | Method for the production and purification of 1,7'-dimethyl-2'-propyl-2,5'-bi-1h-benzimidazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2471730A1 true CA2471730A1 (en) | 2003-07-24 |
| CA2471730C CA2471730C (en) | 2011-03-29 |
Family
ID=7712431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2471730A Expired - Fee Related CA2471730C (en) | 2002-01-18 | 2003-01-15 | Process for preparing and purifying 1,7'-dimethyl-2'-propyl-2,5'-bi-1h-benzimidazole |
Country Status (9)
| Country | Link |
|---|---|
| EP (2) | EP2199286A1 (en) |
| JP (2) | JP5129918B2 (en) |
| CN (1) | CN100436426C (en) |
| AT (1) | ATE465998T1 (en) |
| AU (1) | AU2003235720A1 (en) |
| CA (1) | CA2471730C (en) |
| DE (2) | DE10201725A1 (en) |
| ES (1) | ES2341235T3 (en) |
| WO (1) | WO2003059890A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110190508A1 (en) * | 2008-05-02 | 2011-08-04 | Boehringer Ingelheim International Gmbh | Preparation of 1,7'-dimethyl-2'-propyl-2,5'-bi-1h-benzimidazole |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2414019A (en) * | 2004-05-11 | 2005-11-16 | Cipla Ltd | One-step preparation of telmisartan by condensation and hydrolysis |
| US7943781B2 (en) | 2004-10-18 | 2011-05-17 | Dr. Reddy's Laboratories Limited | Process for preparing telmisartan |
| DE102005034279A1 (en) | 2005-07-22 | 2007-01-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Preparation of 1,7'-dimethyl-2'-propyl-2,5'-bi-1H-benzimidazole |
| CN101172968B (en) * | 2006-11-01 | 2010-05-12 | 浙江天宇药业有限公司 | 2-propyl-4 methyl-6-(tolimidazole-2group) benzoglioxaline salt and method for producing the same |
| CN101717370A (en) * | 2009-11-30 | 2010-06-02 | 常州亚邦制药有限公司 | New method for preparing 2-n-propyl-4-methyl-6-(1-methyl benzimidazole-2-yl) benzimidazole |
| JP6210599B2 (en) * | 2014-02-26 | 2017-10-11 | 株式会社トクヤマ | Process for producing 4-methyl-6 (1-methylbenzimidazol-2-yl) -2-n-propyl-1H-benzimidazole |
| CN104974096B (en) * | 2015-07-07 | 2019-02-01 | 威海迪素制药有限公司 | A kind of preparation method of telmisartan intermediate |
| CN107434786B (en) * | 2016-05-27 | 2025-11-18 | 广东东阳光药业股份有限公司 | Benzimidazole compound and process for producing the same |
| MY200793A (en) | 2017-11-13 | 2024-01-16 | Ecolab Usa Inc | A novel one-pot homogeneous process for the large scale manufacture of 2-substituted benzimidazoles |
| CN111808027A (en) * | 2020-05-25 | 2020-10-23 | 重庆康刻尔制药有限公司 | Purification method of telmisartan intermediate |
| CN114605333A (en) * | 2020-12-04 | 2022-06-10 | 浙江华海药业股份有限公司 | Method for preparing telmisartan intermediate |
| CN115466222B (en) * | 2022-07-28 | 2024-06-04 | 江苏中邦制药有限公司 | Preparation method of telmisartan intermediate |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1225318B (en) * | 1959-09-05 | 1966-09-22 | Bayer Ag | Process for the production of azo dyes and their metal complex compounds |
| DE19917524C2 (en) | 1999-04-17 | 2001-09-20 | Boehringer Ingelheim Pharma | Process for the nitration of aniline derivatives |
-
2002
- 2002-01-18 DE DE10201725A patent/DE10201725A1/en not_active Ceased
-
2003
- 2003-01-15 CA CA2471730A patent/CA2471730C/en not_active Expired - Fee Related
- 2003-01-15 JP JP2003559994A patent/JP5129918B2/en not_active Expired - Lifetime
- 2003-01-15 ES ES03729459T patent/ES2341235T3/en not_active Expired - Lifetime
- 2003-01-15 EP EP10157002A patent/EP2199286A1/en not_active Withdrawn
- 2003-01-15 AU AU2003235720A patent/AU2003235720A1/en not_active Abandoned
- 2003-01-15 DE DE50312660T patent/DE50312660D1/en not_active Expired - Lifetime
- 2003-01-15 EP EP03729459A patent/EP1470111B1/en not_active Expired - Lifetime
- 2003-01-15 WO PCT/EP2003/000319 patent/WO2003059890A1/en not_active Ceased
- 2003-01-15 AT AT03729459T patent/ATE465998T1/en active
- 2003-01-15 CN CNB038024470A patent/CN100436426C/en not_active Expired - Fee Related
-
2010
- 2010-07-23 JP JP2010166115A patent/JP2010241839A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110190508A1 (en) * | 2008-05-02 | 2011-08-04 | Boehringer Ingelheim International Gmbh | Preparation of 1,7'-dimethyl-2'-propyl-2,5'-bi-1h-benzimidazole |
| US8362269B2 (en) * | 2008-05-02 | 2013-01-29 | Boehringer Ingelheim International Gmbh | Preparation of 1,7′-dimethyl-2′-propyl-2,5′-bi-1H-benzimidazole |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1073844A1 (en) | 2005-10-21 |
| ATE465998T1 (en) | 2010-05-15 |
| JP5129918B2 (en) | 2013-01-30 |
| EP1470111B1 (en) | 2010-04-28 |
| WO2003059890A1 (en) | 2003-07-24 |
| EP2199286A1 (en) | 2010-06-23 |
| JP2005529064A (en) | 2005-09-29 |
| CN1620437A (en) | 2005-05-25 |
| AU2003235720A1 (en) | 2003-07-30 |
| ES2341235T3 (en) | 2010-06-17 |
| CA2471730C (en) | 2011-03-29 |
| DE50312660D1 (en) | 2010-06-10 |
| CN100436426C (en) | 2008-11-26 |
| JP2010241839A (en) | 2010-10-28 |
| DE10201725A1 (en) | 2003-08-14 |
| EP1470111A1 (en) | 2004-10-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20170116 |