CN107056756A - A kind of method for preparing high-purity Losartan - Google Patents
A kind of method for preparing high-purity Losartan Download PDFInfo
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- CN107056756A CN107056756A CN201611071298.0A CN201611071298A CN107056756A CN 107056756 A CN107056756 A CN 107056756A CN 201611071298 A CN201611071298 A CN 201611071298A CN 107056756 A CN107056756 A CN 107056756A
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- 0 *C1N(*)C*CC1 Chemical compound *C1N(*)C*CC1 0.000 description 3
- FGCNIDUBRIVYBP-UHFFFAOYSA-N CCCCc1nc(Cl)c(CO)[n]1Cc(cc1)ccc1-c1ccccc1C#N Chemical compound CCCCc1nc(Cl)c(CO)[n]1Cc(cc1)ccc1-c1ccccc1C#N FGCNIDUBRIVYBP-UHFFFAOYSA-N 0.000 description 2
- PSIFNNKUMBGKDQ-UHFFFAOYSA-N CCCCc1nc(Cl)c(CO)[n]1Cc(cc1)ccc1-c1ccccc1-c1nnn[nH]1 Chemical compound CCCCc1nc(Cl)c(CO)[n]1Cc(cc1)ccc1-c1ccccc1-c1nnn[nH]1 PSIFNNKUMBGKDQ-UHFFFAOYSA-N 0.000 description 1
- VCYVKALRJQOLPV-UHFFFAOYSA-N CCCCc1nc(Cl)c(CO)[n]1Cc(cc1)ccc1-c1ccccc1C(C)C#[N]N=N Chemical compound CCCCc1nc(Cl)c(CO)[n]1Cc(cc1)ccc1-c1ccccc1C(C)C#[N]N=N VCYVKALRJQOLPV-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N CCN1CCCCC1 Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N CN1CCCC1 Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a kind of method for preparing high-purity Losartan, and structural formula such as formula A catalyst is added organic solvent by this method, and acid is added dropwise, salt is stirred into；After compound 1, Sodium azide and TBAB, heating stirring reaction are added into the system high-purity Losartan is obtained through post processing.The Losartan obtained using the present invention, purity is high, and outward appearance is good, and purity can reach 98.4%, and list is miscellaneous can be reduced to 0.2%.Using this method, cost is relatively low, high income, while the method for the present invention is simple to operate and friendly to environment, suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of catalyst for synthesizing Losartan and its method using the catalyst preparation Losartan, belong to
Medicine and its intermediate preparing technical field.
Technical background
Losartan Potassium (Losartan Potassium) is that the non-peptides of first listing, orally active specific blood vessels are tight
Plain II (AT1) receptor antagonist is opened, has the advantages that medication is convenient, antihypertensive effect is notable, Small side effects.In recent years, Losartan
Potassium is always the key agents for being clinically used for treating hypertension.
Losartan is its free state or back intermediate, and chemistry is entitled：{ the chloro- 1- of the 2- butyl -4- [2 '-(nitrogen of 1H- tetra-
Azoles -5- bases) biphenyl -4- bases] methyl isophthalic acid H- imidazoles -5- bases } methanol.Its salt or alkali reaction with potassium hydroxide etc. containing potassium i.e. can be with
Obtain Losartan Potassium.
Catalyst used in synthesis Losartan reported in the literature is generally ammonium salt, zinc salt or triethylamine salt etc., gained chlorine
Husky smooth purity is generally 96-97%, and outward appearance is poor, and follow-up synthesis Losartan Potassium needs repeatedly to decolourize just obtain up-to-standard
Losartan Potassium.The present invention provides a kind of catalyst and its method with the catalyst preparation Losartan for preparing Losartan, should
Convenient catalyst is easy to get, and is prepared into it that Losartan purity is high, outward appearance is good, and synthesis technique is applicable industrial production and can produce warp
Ji benefit.
The content of the invention
It is an object of the invention to provide a kind of method for preparing high-purity Losartan, this method comprises the following steps：
1) structural formula such as formula A catalyst is added into organic solvent, acid is added dropwise, salt is stirred into；
2) compound 1, Sodium azide and TBAB are added into above-mentioned system, heat up stirring reaction；
3) above-mentioned reactant mixture is cooled, adds sodium hydroxide solution and water, carry out saponification；
4) stand and natrium nitrosum and water are added in a point liquid, aqueous phase, stirring；
5) cool, add hydrochloric acid and be acidified, and add ethyl acetate and disperseed, stirring and crystallizing；
6) suction filtration, dries to obtain Losartan.
R in the formula A1Base is hydrogen, C1~C4Alkyl, C6~C10Aromatic radical, R2Base is hydrogen, C1~C4Alkyl,
C6~C10Aromatic radical, n be 1 or 2.
The chemistry of compound 1 is entitled：4 '-((2- butyl -4- chloro- 5- (methylol) -1H- imidazoles -1- bases) methyl)-[1,1 ' -
Biphenyl] -2- nitriles, it can be also simply referred to as chlorine nitrile.
The step 1) in used acid can be the one kind or organic acid of inorganic acid in sulfuric acid, hydrochloric acid
One kind in acetic acid, trifluoroacetic acid, oxalic acid, sulfonic acid；
The step 1) in used catalyst and acid molar ratio be 1：1~2：1；
The step 1) in organic solvent used be aromatic hydrocarbon solvent, such as toluene, dimethylbenzene, chlorobenzene；
The step 1) in the used volume of organic solvent and the mass ratio of input compound 1 be 2：1 (V/W)~3：1
(V/W) it is preferably, 2.4：1；
The step 2) in compound 1, Sodium azide input amount molar ratio be 1：2.0~1：2.5, preferably 1：2.3；Four
The mol ratio of butylammonium bromide and Sodium azide input amount is：1：12.5~1：25, preferably 1：23；
The step 3) in cooling temperature range be 45~60 DEG C, preferably 50-55 DEG C；
The step 4) in stirring time be 10~30min, preferably 20min；
The step 5) in cooling temperature range be 20~35 DEG C, preferably 25-30 DEG C；
The step 5) in stirring and crystallizing time be 2~5h, preferably 3h；
The step 6) in drying temperature be 55~85 DEG C, preferably 65-70 DEG C, drying time is 12-24h, preferably
For 16-18h.
The preparation of chlorine nitrile：The compound 1 can refer to patent document WO2007133040A1 by biphenyl bromide and imidazoles
Aldehyde carries out condensation reaction in the presence of alkali, then adds reducing agent sodium borohydride or potassium borohydride is reduced to aldehyde radical, ties
Crystalline substance filters, is dried to obtain compound shown in formula 1.Reaction equation is as follows：
The Losartan that the catalyst provided using the present invention is obtained, purity is high, and outward appearance is good, and purity can reach 98.4%,
List is miscellaneous can be reduced to 0.2%.Using this method, cost is relatively low, high income, while the method for the present invention is simple to operate, environment
Close friend, suitable for industrialized production.
Specific embodiment
The present invention is further elaborated with reference to embodiment, but these examples do not constitute any limit to the present invention
System.
Embodiment 1：
27.2g nafoxidines and 160mL toluene are sequentially added into a 1000ml four-hole bottles, stirring is opened.Dropwise to it
The middle addition 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h.Sequentially added into gained mixed system chlorine nitrile 66.0g, Sodium azide 26.0g and
TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, 45mL hydroxides are added into reaction system
Sodium solution and 220mL drinking water, saponification 1h.Divide and go upper toluene phase, and washing is drunk with 15mL sodium hydroxide solutions and 90mL
Toluene phase is washed, merges aqueous phase, 15g natrium nitrosums is added and 25mL quotes water, stirring.25 DEG C are cooled to, is added dropwise into mixed liquor
6N salt acid for adjusting pH is 7.0, adds 230mL ethyl acetate, stirring.It is 4.0, stirring and crystallizing to continue that 6N salt acid for adjusting pH is added dropwise
3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is 90%, and purity is
98.4%.
Embodiment 2：
27.2g nafoxidines and 160mL dimethylbenzene are sequentially added into a 1000ml four-hole bottles, stirring is opened.Dropwise to
Wherein add the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h.Chlorine nitrile 66.0g, Sodium azide 26.0g are sequentially added into gained mixed system
With TBAB 0.8g, 95 DEG C, stirring reaction 42h are warming up to.50 DEG C are cooled to, 45mL hydrogen-oxygens are added into reaction system
Change sodium solution and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions and 90mL drinking water
Toluene phase is washed, merges aqueous phase, 15g natrium nitrosums is added and 25mL quotes water, stirring.25 DEG C are cooled to, is dripped into mixed liquor
Plus 6N salt acid for adjusting pH is 7.0,230mL ethyl acetate, stirring are added.It is 4.0, stirring and crystallizing to continue that 6N salt acid for adjusting pH is added dropwise
3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is 80.3%, and purity is
97.0%.
Embodiment 3：
27.2g nafoxidines and 160mL dimethylbenzene are sequentially added into a 1000ml four-hole bottles, stirring is opened.Dropwise to
Wherein add 43.7g trifluoroacetic acids, 25 DEG C of stirring 2h.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
78.6%, purity is 96.8%.
Embodiment 4：
1- methyl nafoxidine 32.6g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.By
Drop adds the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h thereto.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
84.5%, purity is 97.8%.
Embodiment 5：
1- phenyl nafoxidine 56.3g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.By
Drop adds the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h thereto.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
82.6%, purity is 97.2%.
Embodiment 6：
2- methyl nafoxidine 32.6g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.By
Drop adds the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h thereto.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
87.0%, purity is 98.1%.
Embodiment 7：
Hexahydropyridine 32.6g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.Dropwise to it
The middle addition 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h.Sequentially added into gained mixed system chlorine nitrile 66.0g, Sodium azide 26.0g and
TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, 45mL hydroxides are added into reaction system
Sodium solution and 220mL drinking water, saponification 1h.Divide and go upper toluene phase, and washing is drunk with 15mL sodium hydroxide solutions and 90mL
Toluene phase is washed, merges aqueous phase, 15g natrium nitrosums is added and 25mL quotes water, stirring.25 DEG C are cooled to, is added dropwise into mixed liquor
6N salt acid for adjusting pH is 7.0, adds 230mL ethyl acetate, stirring.It is 4.0, stirring and crystallizing to continue that 6N salt acid for adjusting pH is added dropwise
3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is 88.2%, and purity is
97.9%.
Embodiment 8：
1- methyl piperidine 37.9g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.By
Drop adds the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h thereto.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
86.1%, purity is 97.6%.
Embodiment 9：
1- ethyl piperidine 43.3g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.By
Drop adds the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h thereto.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
84.0%, purity is 97.2%.
Embodiment 10：
1- methyl piperidine 37.9g and 160mL toluene is sequentially added into a 1000ml four-hole bottles, stirring is opened.By
Drop adds the 19.0g concentrated sulfuric acids, 25 DEG C of stirring 2h thereto.Chlorine nitrile 66.0g, Sodium azide are sequentially added into gained mixed system
26.0g and TBAB 0.8g, is warming up to 95 DEG C, stirring reaction 42h.50 DEG C are cooled to, is added into reaction system
45mL sodium hydroxide solutions and 220mL drinking water, saponification 1h.Point go upper toluene phase, and with 15mL sodium hydroxide solutions with
90mL drinks water washing toluene phase, merges aqueous phase, adds 15g natrium nitrosums and 25mL quotes water, stirring.25 DEG C are cooled to, to
It is 7.0 that 6N salt acid for adjusting pH is added dropwise in mixed liquor, adds 230mL ethyl acetate, stirring.Continuing dropwise addition 6N salt acid for adjusting pH is
4.0, stirring and crystallizing 3h.Suction filtration, filter cake is eluted with ethyl acetate.Filter cake is collected, 65 DEG C of decompression dryings obtain Losartan.Yield is
84.4%, purity is 97.3%.
Claims (10)
1. a kind of method for preparing high-purity Losartan, it is characterised in that this method comprises the following steps：
1) structural formula such as formula A catalyst is added into organic solvent, acid is added dropwise, salt is stirred into；
2) compound 1, Sodium azide and TBAB are added into above-mentioned system, heat up stirring reaction；
3) above-mentioned reactant mixture is cooled, adds liquid caustic soda and water, carry out saponification；
4) stand and natrium nitrosum and water are added in a point liquid, aqueous phase, stirring；
5) cool, add hydrochloric acid and be acidified, and add ethyl acetate and disperseed, stirring and crystallizing；
6) suction filtration, dries to obtain Losartan；
R in wherein formula A1Base is selected from hydrogen, C1~C4Alkyl, C6~C10Aromatic radical, R2Base is selected from hydrogen, C1~C4Alkyl, C6
~C10Aromatic radical, n be 1 or 2.
2. prepare the method for high-purity Losartan as claimed in claim 1, it is characterised in that step 1) in used acid can be with
For the one kind of inorganic acid in sulfuric acid, hydrochloric acid, or organic acid in acetic acid, trifluoroacetic acid, oxalic acid, sulfonic acid one
Kind.
3. as claimed in claim 1 prepare high-purity Losartan method, it is characterised in that step 1) in used catalyst and
The molar ratio of inorganic acid is 1：1~2：1.
4. prepare the method for high-purity Losartan as described in claim 1, it is characterised in that step 1) in it is used organic molten
Agent is aromatic hydrocarbon solvent, preferably toluene, dimethylbenzene, chlorobenzene.
5. prepare the method for high-purity Losartan as described in claim 1, it is characterised in that step 1) in it is used organic
The mass ratio of the volume of solvent and input compound 1 is 2：1 (V/W)~3：1 (V/W), preferably 2.4：1.
6. as described in claim 1 prepare high-purity Losartan method, it is characterised in that the step 2) in compound
1st, Sodium azide input amount molar ratio is 1：2.0~1：2.5, preferably 1：2.3；TBAB and Sodium azide input amount
Mol ratio is 1：12.5~1：25, preferably 1：23.
7. the temperature range of cooling is 45~60 DEG C according to the method described in claim 1, it is characterised in that the step 3),
Preferably 50-55 DEG C.
8. the method for high-purity Losartan is prepared as described in claim 1, it is characterised in that the step 4) middle stirring
Time is 10~30min, preferably 20min.
9. the method for high-purity Losartan is prepared as described in claim 1, it is characterised in that the step 5) middle cooling
Temperature range is 20~35 DEG C, preferably 25-30 DEG C；The time of stirring and crystallizing is 2~5h, preferably 3h.
10. the method for high-purity Losartan is prepared as described in claim 1, it is characterised in that the step 6) middle drying
Temperature is 55~85 DEG C, and preferably 65-70 DEG C, drying time is 12-24h, preferably 16-18h.
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Cited By (4)
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| CN110467604A (en) * | 2019-08-29 | 2019-11-19 | 浙江天宇药业股份有限公司 | A kind of preparation method of Losartan |
| CN113372338A (en) * | 2021-07-03 | 2021-09-10 | 润都制药(荆门)有限公司 | Preparation method of losartan impurity |
| WO2023116514A1 (en) * | 2021-12-22 | 2023-06-29 | 浙江华海药业股份有限公司 | High-purity losartan potassium and preparation method therefor |
| WO2023116515A1 (en) * | 2021-12-22 | 2023-06-29 | 浙江华海药业股份有限公司 | Method for preparing high-purity losartan |
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| WO2010029457A2 (en) * | 2008-09-09 | 2010-03-18 | Alembic Limited | An improved process for preparing losartan potassium |
| CN102675294A (en) * | 2012-05-17 | 2012-09-19 | 浙江天宇药业股份有限公司 | Method of synthesizing losartan and losartan intermediates |
| CN105198863A (en) * | 2015-10-30 | 2015-12-30 | 浙江华海药业股份有限公司 | Method for preparing high-purity losartan |
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| WO2010029457A2 (en) * | 2008-09-09 | 2010-03-18 | Alembic Limited | An improved process for preparing losartan potassium |
| CN102675294A (en) * | 2012-05-17 | 2012-09-19 | 浙江天宇药业股份有限公司 | Method of synthesizing losartan and losartan intermediates |
| CN105198863A (en) * | 2015-10-30 | 2015-12-30 | 浙江华海药业股份有限公司 | Method for preparing high-purity losartan |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110467604A (en) * | 2019-08-29 | 2019-11-19 | 浙江天宇药业股份有限公司 | A kind of preparation method of Losartan |
| CN110467604B (en) * | 2019-08-29 | 2020-09-08 | 浙江天宇药业股份有限公司 | Preparation method of losartan |
| WO2021036193A1 (en) * | 2019-08-29 | 2021-03-04 | 浙江天宇药业股份有限公司 | Preparation method for losartan |
| JP2022545581A (en) * | 2019-08-29 | 2022-10-27 | 浙江天宇薬業股▲ふん▼有限公司 | Manufacturing method of losartan |
| JP7267508B2 (en) | 2019-08-29 | 2023-05-01 | 浙江天宇薬業股▲ふん▼有限公司 | Manufacturing method of losartan |
| CN113372338A (en) * | 2021-07-03 | 2021-09-10 | 润都制药(荆门)有限公司 | Preparation method of losartan impurity |
| WO2023116514A1 (en) * | 2021-12-22 | 2023-06-29 | 浙江华海药业股份有限公司 | High-purity losartan potassium and preparation method therefor |
| WO2023116515A1 (en) * | 2021-12-22 | 2023-06-29 | 浙江华海药业股份有限公司 | Method for preparing high-purity losartan |
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| CN107056756B (en) | 2021-01-05 |
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