CN104262237A - Synthesis method of amlodipine free alkali - Google Patents
Synthesis method of amlodipine free alkali Download PDFInfo
- Publication number
- CN104262237A CN104262237A CN201410513655.9A CN201410513655A CN104262237A CN 104262237 A CN104262237 A CN 104262237A CN 201410513655 A CN201410513655 A CN 201410513655A CN 104262237 A CN104262237 A CN 104262237A
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- CN
- China
- Prior art keywords
- free alkali
- amlodipine
- amlodipine free
- synthesis method
- sodium hydroxide
- 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.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
The invention relates to a synthesis method of amlodipine free alkali. According to the synthesis method of the amlodipine free alkali, phthaloyl amlodipine is used as a raw material and is hydrolyzed by a sodium hydroxide aqueous solution under the condition of room temperature to prepare the amlodipine free alkali. By virtue of the synthesis method of the amlodipine free alkali, the 5% sodium hydroxide aqueous solution is used as a reaction solution, so that the economy is obviously improved; the synthesis method of the amlodipine free alkali is relatively environmental friendly and stable; the economy is improved; the yield is obviously improved.
Description
Technical field
The present invention relates to field of chemical pharmacy, especially a kind of synthetic method of amlodipine free alkali.
Background technology
Amlodipine (alkali), chemical name: (±)-2-(the amino ethoxymethyl of 2-)-4-(2-chloro-phenyl-)-3-ethoxycarboxy-5-methoxy carboxyl-6-methyl isophthalic acid, 4-dihydropyridine,
Structural formula is as follows:
Medicine after the sour salifies such as amlodipine (alkali) and Phenylsulfonic acid, hydrochloric acid, toxilic acid is dihydropyridine type calcium antagonists (calcium ion antagonist or slow channel blocking agent).Calcium antagonist is also known as calcium channel blocker, and be a line basis depressor, clinical application is extensive.Calcium antagonist has broad variety, and respective pharmacokinetics, pharmacodynamics feature are obviously different.The chemical structure of amlodipine is similar to nifedipine, but has unique pharmacological characteristics, be the 3rd generation calcium antagonist representative.Its superiority is that onset is slow, and acting duration is long, convenient drug administration, few side effects.Due to unique texture and the pharmacological property of amlodipine, treatment hypertension and stenocardia are widely used in.
The synthetic method of existing amlodipine (alkali), with phthaloyl amlodipine and 80% hydrazine hydrate aqueous solution for raw material, 40 DEG C of reactions 12 hours, obtains after centrifugal washing, yield 80 ~ 85%.
In the method for above-mentioned use phthaloyl amlodipine and the reaction of 80% hydrazine hydrate aqueous solution, use and there is toxicity and explosive hydrazine hydrate aqueous solution, significantly can increase production, safety features and environmental protection treatment cost.
Summary of the invention
The technical problem to be solved in the present invention is: in order to provide a kind of synthetic method of amlodipine free alkali, and preparation technology is simple, and cost of manufacture is low, and product content is high, pollution-free.
The technical solution adopted for the present invention to solve the technical problems is: a kind of synthetic method of amlodipine free alkali, uses phthaloyl amlodipine raw material, is hydrolyzed into amlodipine free alkali at ambient temperature through aqueous sodium hydroxide solution.
Reaction formula is as follows:
As preferably, in described aqueous sodium hydroxide solution, the content of sodium hydroxide is 5%.
As preferably, the weight ratio of described phthaloyl amlodipine and aqueous sodium hydroxide solution is 1: 2-1: 4.
As preferably, hydrolysis time is 5-8 hour.
The invention has the beneficial effects as follows:
(1) former technique uses 80% hydrazine hydrate aqueous solution now to use 5% aqueous sodium hydroxide solution instead as reaction solution, and economy significantly improves;
(2) 80% a large amount of hydrazine hydrate aqueous solutions has higher danger and toxicity, and 5% aqueous sodium hydroxide solution relative environmental protection is stablized;
(3) the by product disodium phthalate produced has certain economy;
(4) temperature of reaction can reduce in the milder reaction times, improves economy;
(5) yield significantly improves.
Embodiment
Embodiment 1:
Drop in reactor after 420kg5% aqueous sodium hydroxide solution and 130kg disodium phthalate are weighed, open and stir, at room temperature react 6 hours, put into centrifuge, disodium phthalate is removed in washing, obtain amlodipine (alkali) 100kg, productive rate 93.5%, content more than 99%.
Embodiment 2:
Drop in reactor after 440kg5% aqueous sodium hydroxide solution and 120kg disodium phthalate are weighed, open and stir, at room temperature react 5 hours, put into centrifuge, disodium phthalate is removed in washing, obtain amlodipine (alkali) 95kg, productive rate 92.3%, content more than 99%.
With above-mentioned according to desirable embodiment of the present invention for enlightenment, by above-mentioned description, relevant staff in the scope not departing from this invention technological thought, can carry out various change and amendment completely.The technical scope of this invention is not limited to the content on specification sheets, must determine its technical scope according to right.
Claims (4)
1. a synthetic method for amlodipine free alkali, is characterized in that: use phthaloyl amlodipine raw material, be hydrolyzed into amlodipine free alkali at ambient temperature through aqueous sodium hydroxide solution.
2. the synthetic method of amlodipine free alkali as claimed in claim 1, is characterized in that: in described aqueous sodium hydroxide solution, the content of sodium hydroxide is 5%.
3. the synthetic method of amlodipine free alkali as claimed in claim 1, is characterized in that: the weight ratio of described phthaloyl amlodipine and aqueous sodium hydroxide solution is 1: 2-1: 4.
4. the synthetic method of amlodipine free alkali as claimed in claim 1, is characterized in that: the reaction times is 5-8 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410513655.9A CN104262237A (en) | 2014-09-28 | 2014-09-28 | Synthesis method of amlodipine free alkali |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410513655.9A CN104262237A (en) | 2014-09-28 | 2014-09-28 | Synthesis method of amlodipine free alkali |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104262237A true CN104262237A (en) | 2015-01-07 |
Family
ID=52153856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410513655.9A Pending CN104262237A (en) | 2014-09-28 | 2014-09-28 | Synthesis method of amlodipine free alkali |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104262237A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4572909A (en) * | 1982-03-11 | 1986-02-25 | Pfizer Inc. | 2-(Secondary aminoalkoxymethyl) dihydropyridine derivatives as anti-ischaemic and antihypertensive agents |
| HRP20000490A2 (en) * | 2000-07-21 | 2002-02-28 | Belupo Lijekovi I Kozmetika D | Process for the preparation of amlodipine besilate |
| CN1352634A (en) * | 1999-07-05 | 2002-06-05 | 里克特格登化工有限公司 | Process for preparing amlodipine benzenesulphonate |
| WO2004058711A1 (en) * | 2002-12-30 | 2004-07-15 | Eos Eczacibasi Ozgun Kimyasal Urunler Sanayi Ve Ticaret A.S. | Isolation of dihydropyridine derivative and preparation salts thereof |
-
2014
- 2014-09-28 CN CN201410513655.9A patent/CN104262237A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4572909A (en) * | 1982-03-11 | 1986-02-25 | Pfizer Inc. | 2-(Secondary aminoalkoxymethyl) dihydropyridine derivatives as anti-ischaemic and antihypertensive agents |
| CN1352634A (en) * | 1999-07-05 | 2002-06-05 | 里克特格登化工有限公司 | Process for preparing amlodipine benzenesulphonate |
| HRP20000490A2 (en) * | 2000-07-21 | 2002-02-28 | Belupo Lijekovi I Kozmetika D | Process for the preparation of amlodipine besilate |
| WO2004058711A1 (en) * | 2002-12-30 | 2004-07-15 | Eos Eczacibasi Ozgun Kimyasal Urunler Sanayi Ve Ticaret A.S. | Isolation of dihydropyridine derivative and preparation salts thereof |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150107 |