CS216226B2 - Method of making the forms of hydrochloride 2-+l 4-+l2-furoyl+p-piperazin-1-yl+p-4-amino-6,7-dimethoxychinazoline - Google Patents
Method of making the forms of hydrochloride 2-+l 4-+l2-furoyl+p-piperazin-1-yl+p-4-amino-6,7-dimethoxychinazoline Download PDFInfo
- Publication number
- CS216226B2 CS216226B2 CS811167A CS116781A CS216226B2 CS 216226 B2 CS216226 B2 CS 216226B2 CS 811167 A CS811167 A CS 811167A CS 116781 A CS116781 A CS 116781A CS 216226 B2 CS216226 B2 CS 216226B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- hydrochloride
- furoyl
- amino
- piperazin
- water
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- WFXFYZULCQKPIP-UHFFFAOYSA-N prazosin hydrochloride Chemical compound [H+].[Cl-].N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 WFXFYZULCQKPIP-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- -1 2-furoyl Chemical group 0.000 claims 2
- 239000007858 starting material Substances 0.000 claims 1
- 229960002386 prazosin hydrochloride Drugs 0.000 description 11
- 229960001289 prazosin Drugs 0.000 description 3
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 3
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Vynález se týká způsobu výroby formy a . hydrochloridu prazosinu, tj. hydrochloridu 2- [ 4- (2-furoyl )-piperazin-l-yl ) -4-amino-6,7-dimethoxychinazolinu vzorceThe invention relates to a process for the manufacture of a mold. prazosin hydrochloride, i.e. 2- [4- (2-furoyl) -piperazin-1-yl) -4-amino-6,7-dimethoxyquinazoline hydrochloride of the formula
Podle vynálezu se forma a vyrábí tak, že se krystalová' voda z hydrátu hydrochloridu prazosinu odstraní azeotropickou destilací pomocí dichlormethanu. Po odstranění veškeré vody zůstává čistá forma a hydrochloridu prazosinu.According to the invention, form a is produced by removing crystalline water from prazosin hydrochloride hydrate by azeotropic distillation with dichloromethane. After removal of all the water, the prazosin hydrochloride form remains pure.
Prazosin je známé léčivo používané ke snížení krevního tlaku. Ve zveřejněné finské patentové přihlášce č. 77 0634, jíž je ekvivalentní americký patentový spis č. 4 092 315, je popisována krystalická forma bezvodého hydrochloridu prazosinu, která se označuje jako α-prazosinhydrochlorid. Udává se, že forma a má jisté výhody ve srovnání s jinými krystalovými formami [viz uvedenou finskou patentovou přihlášku č. 77 0634, str. 15)· ,Prazosin is a known drug used to lower blood pressure. Finnish Patent Application Publication No. 77 0634, which is equivalent to U.S. Patent No. 4,092,315, describes a crystalline form of prazosin hydrochloride anhydrous, which is referred to as α-prazosine hydrochloride. Form a is said to have certain advantages over other crystal forms (see Finnish Patent Application No. 77 0634, p. 15),
Z uvedené publikace je dále známé vyrábět formu a tím, že se některé jiné krystalové formy zahřívají při vysoké teplotě (100 až 200 °C] v organickém rozpouštědle, zejména v alkoholu s 5 až 7 atomy uhlíku.It is further known from said publication to produce a mold and in that some other crystal forms are heated at a high temperature (100 to 200 ° C) in an organic solvent, in particular in an alcohol having 5 to 7 carbon atoms.
Způsob výroby formy hydrochloridu prazosinu, popsaný v uvedené finské patentové přihlášce č. 77 0634, má některé nevýhody. Při vysoké teplotě se prazosin může již částečně rozkládat, což může v produktu tvořit nečistoty a snižovat výtěžek. Vzniká také nebezpečí, že se místo formy a získá forma χ nazývaná krystalický polymorf (viz uvedenou finskou patentovou přihlášku č. 77 0634, str. 7). Mimo to odstraňování rozpouštědel s vysokou teplotou varu z produktu může být obtížné.The process for the preparation of the form of prazosin hydrochloride described in the aforementioned Finnish Patent Application No. 77 0634 has some disadvantages. At high temperature, prazosin may already partially decompose, which may form impurities in the product and reduce the yield. There is also the danger that a form called crystalline polymorph is obtained instead of form a (see Finnish Patent Application No. 77 0634, p. 7). In addition, removal of high boiling solvents from the product can be difficult.
Zjistilo se, že se čistá forma a hydrochloridu prazosinu může s kvantitativním výtěžkem a velmi jednoduše vyrábět tak, že se voda z' hydrátu hydrochloridu prazosinu nebo z hydrátu ' hydrochloridu prazosinu obsahujícího vopu odstraní azeotropickou destilací pomocí dichlormethanu a uvolněná voda se ., oddělí odlučovačem vody. Bylo zjištěno, že se při tom tvoří pouze forma a hydrochloridu prazosinu. Produkt byl identifikován na základě svého IČ spektra.It has been found that the pure form a of prazosin hydrochloride can be produced in quantitative yield and very simply by removing water from prazosin hydrochloride hydrate or from prazosin hydrochloride hydrate containing azeotropic distillation with dichloromethane and separating the released water with a water separator. . It has been found that only the form a of prazosin hydrochloride is formed. The product was identified by its IR spectrum.
Způsob podle vynálezu je příznivý především pro nízkou teplotu (kolem 42 °C). Další výhodou je to, že je dichlormethan levným, snadno regenerovatelným a pro průmyslový provoz velmi vhodným rozpouštědlem. Nebylo zjištěno, že by při způsobu podle vynálezu vzpikaly nečistoty.The process of the invention is particularly favorable for low temperature (about 42 ° C). Another advantage is that dichloromethane is a low-cost, easily regenerable and highly suitable solvent for industrial operation. Impurities have not been found to leak in the process of the invention.
Vynález je blíže objasňován v následujících příkladech jeho konkrétního provedení.The invention is illustrated by the following examples.
Příklad 1Example 1
228 g (0,5 mol) dihydrátu hydrochloridu prazosinu, vyrobeného podle zveřejněné finské patentové přihlášky . č. 79 0320 (ekvivalentní je NSR patentový spis č. 3 002 553), se rozplaví ve 2200 ml dichlormethanu. Na . reakční nádobu se připojí odlučovač vody a směs se pod zpětným chladičem vaří tak dlouho, až se neodlučuje žádná voda (asi 4 až 6 hodin). Zbytek se odfiltruje a zbylý dichlormethan se odpaří při sníženém tlaku.228 g (0.5 mol) of prazosin hydrochloride dihydrate produced according to the published Finnish patent application. No. 79,020 (equivalent to German Patent No. 3,002,553), is dissolved in 2200 ml of dichloromethane. On . a water separator is connected to the reaction vessel and the mixture is refluxed until no water is separated (about 4-6 hours). The residue was filtered off and the remaining dichloromethane was evaporated under reduced pressure.
Výtěžek je 210 g (100 °/o teorie) hydrochloridu prazosinu [teplota rozkladu je 280 až 282 °C, IČ (KBr): 3319, 3226, 3077, 2857, 1634, 1597, 1481, 1468, 1425, 1280, 794, 763, 751, 721, 717, 675 cm!]. iC spektrum je stejné se spektrem formy a popsaným . ve shora uvedené finské patentové přihlášce č. ' 77 0634.Yield: 210 g (100% of theory) of prazosin hydrochloride (decomposition temperature 280-282 ° C, IR (KBr): 3319, 3226, 3077, 2857, 1634, 1597, 1481, 1468, 1425, 1280, 794, 763, 751, 721, 717, 675 cm -1]. The IC spectrum is the same as that of the form described. in the aforementioned Finnish Patent Application No. '77 0634.
P-ř-íkla'd 2P-i-2
300 g nesušeného, z vodného prostředí filtrovaného a vodou promytého hydrochloridu prazosinu (obsahuje 30 % vody — stanoveno postupem podle Karla Fischera) - se rozplaví ve 2200 ml dichlormethanu a postupuje se podle příkladu č. 1. Výtěžek je 210 g (100 - % teorie) α-hydrochloridu. prazosinu.300 g of dried, aqueous filtered and water-washed prazosin hydrochloride (containing 30% water - determined by Karl Fischer method) - are dissolved in 2200 ml of dichloromethane and proceeded as in Example 1. Yield 210 g (100% of theory). ) α-hydrochloride. prazosin.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI800556A FI64367C (en) | 1980-02-26 | 1980-02-26 | OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS216226B2 true CS216226B2 (en) | 1982-10-29 |
Family
ID=8513276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS811167A CS216226B2 (en) | 1980-02-26 | 1981-02-18 | Method of making the forms of hydrochloride 2-+l 4-+l2-furoyl+p-piperazin-1-yl+p-4-amino-6,7-dimethoxychinazoline |
Country Status (11)
| Country | Link |
|---|---|
| CS (1) | CS216226B2 (en) |
| DD (1) | DD156532A5 (en) |
| DK (1) | DK157548C (en) |
| ES (1) | ES8201577A1 (en) |
| FI (1) | FI64367C (en) |
| HU (1) | HU182297B (en) |
| NO (1) | NO154461C (en) |
| PL (1) | PL128350B1 (en) |
| PT (1) | PT72511B (en) |
| SE (1) | SE431873B (en) |
| SU (1) | SU980621A3 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI79107C (en) * | 1984-06-25 | 1989-11-10 | Orion Yhtymae Oy | Process for the preparation of stable form of prazosin hydrochloride. |
| ES2210384T3 (en) * | 1995-09-06 | 2004-07-01 | Kowa Co. Ltd. | DERIVATIVES OF PYRIMIDINE. |
-
1980
- 1980-02-26 FI FI800556A patent/FI64367C/en not_active IP Right Cessation
-
1981
- 1981-02-16 PT PT72511A patent/PT72511B/en not_active IP Right Cessation
- 1981-02-18 CS CS811167A patent/CS216226B2/en unknown
- 1981-02-20 NO NO810590A patent/NO154461C/en unknown
- 1981-02-23 DD DD81227817A patent/DD156532A5/en not_active IP Right Cessation
- 1981-02-25 DK DK084581A patent/DK157548C/en not_active IP Right Cessation
- 1981-02-25 PL PL1981229865A patent/PL128350B1/en unknown
- 1981-02-25 SU SU813247560A patent/SU980621A3/en active
- 1981-02-25 ES ES499796A patent/ES8201577A1/en not_active Expired
- 1981-02-25 HU HU81460A patent/HU182297B/en not_active IP Right Cessation
- 1981-02-26 SE SE8101265A patent/SE431873B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DK84581A (en) | 1981-08-27 |
| ES499796A0 (en) | 1981-12-16 |
| PL229865A1 (en) | 1981-10-30 |
| PT72511A (en) | 1981-03-01 |
| HU182297B (en) | 1983-12-28 |
| DK157548C (en) | 1990-06-11 |
| DD156532A5 (en) | 1982-09-01 |
| FI800556A7 (en) | 1981-08-27 |
| NO810590L (en) | 1981-08-27 |
| ES8201577A1 (en) | 1981-12-16 |
| FI64367C (en) | 1986-08-05 |
| NO154461C (en) | 1986-09-24 |
| FI64367B (en) | 1983-07-29 |
| DK157548B (en) | 1990-01-22 |
| SU980621A3 (en) | 1982-12-07 |
| PT72511B (en) | 1983-02-01 |
| SE431873B (en) | 1984-03-05 |
| SE8101265L (en) | 1981-08-27 |
| PL128350B1 (en) | 1984-01-31 |
| NO154461B (en) | 1986-06-16 |
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