CS272574B1 - Method of selegiline hydrochloride production - Google Patents
Method of selegiline hydrochloride production Download PDFInfo
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- CS272574B1 CS272574B1 CS370888A CS370888A CS272574B1 CS 272574 B1 CS272574 B1 CS 272574B1 CS 370888 A CS370888 A CS 370888A CS 370888 A CS370888 A CS 370888A CS 272574 B1 CS272574 B1 CS 272574B1
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- selegiline hydrochloride
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- selegiline
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- 229960003678 selegiline hydrochloride Drugs 0.000 title claims abstract description 6
- IYETZZCWLLUHIJ-UHFFFAOYSA-N methyl-(1-phenylpropan-2-yl)-prop-2-ynylazanium;chloride Chemical compound Cl.C#CCN(C)C(C)CC1=CC=CC=C1 IYETZZCWLLUHIJ-UHFFFAOYSA-N 0.000 title claims abstract description 4
- 238000000034 method Methods 0.000 title claims description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 9
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims abstract description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 7
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims abstract description 7
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 5
- -1 propargyloxy-triphenylphosphonium chloride Chemical compound 0.000 claims description 4
- 239000003495 polar organic solvent Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 abstract description 7
- 230000000648 anti-parkinson Effects 0.000 abstract 1
- 229950005499 carbon tetrachloride Drugs 0.000 abstract 1
- 231100000053 low toxicity Toxicity 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229960001252 methamphetamine Drugs 0.000 description 4
- 229960003946 selegiline Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 3
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- HTEJLXYOJZOXKM-UHFFFAOYSA-N 1,1-dibromoprop-1-ene Chemical compound CC=C(Br)Br HTEJLXYOJZOXKM-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CKWAHIDVXZGPES-UHFFFAOYSA-N 2-chloropropylbenzene Chemical compound CC(Cl)CC1=CC=CC=C1 CKWAHIDVXZGPES-UHFFFAOYSA-N 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- HQFYIDOMCULPIW-UHFFFAOYSA-N n-methylprop-2-yn-1-amine Chemical compound CNCC#C HQFYIDOMCULPIW-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- IJNJLGFTSIAHEA-UHFFFAOYSA-N prop-2-ynal Chemical compound O=CC#C IJNJLGFTSIAHEA-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Vynález se týká způsobu výroby hydrochloridu selegilinu vzorce I un-jThe invention relates to a process for the preparation of selegiline hydrochloride of formula I un-j
I 3 I 3
C,H,-CH„-CH-N-CH0-C=CH . HClC, H, -CH 2 -CH-N-CH 0 -C = CH. HCl
5 2 i 2 (I)5 2 i 2
CHCH
Sůl vzorce I je známá a zvláště ve formě (R)-(-)-enantiomeru je selektivním MAO B inhibitorem, který se používá při léěbě Parkinsonovy choroby.The salt of formula I is known and in particular in the form of the (R) - (-) - enantiomer is a selective MAO B inhibitor that is used in the treatment of Parkinson's disease.
Podle známého způsobu z literatury se selegilin vyrábí tak (britský patent č. 1 031 425, Rakouský patent č. 271 437), že se methamfetamin zahřívá na 100 °C s dibrompropenem po dobu 7 h, a produkt reakce se působením vroucího roztoku hydroxidu draselného během 16 h dehydrobromuje a isomerizuje. Nevýhodou postupu je velká pracnost výroby a technologická náročnost. Podle jiného postupu (Neth. Appl. Č. 6 605 956, Rakouský patent č. 251 560) se methamfetamin a propargylaldehyd podrobí kondenzaci a následné redukci hliníkovou amalgamou. V tomto případě je nevýhodou nutnost pracovat se silně dráždivým a nestálým aldehydem. Podle dalšího postupu (Rakouský patent S.According to the known literature method, selegiline is produced (British Patent No. 1,031,425, Austrian Patent No. 271,437) by heating methamphetamine at 100 ° C with dibromopropene for 7 hours, and the reaction product is treated with boiling potassium hydroxide solution. it dehydrobromises and isomerizes within 16 h. The disadvantage of the process is the high labor intensity and technological demands. According to another method (Neth. Appl. No. 6,605,956, Austrian Patent No. 251,560), methamphetamine and propargylaldehyde are subjected to condensation and subsequent reduction with aluminum amalgam. In this case, the disadvantage is the need to work with a strongly irritating and volatile aldehyde. According to a further procedure (Austrian patent S.
252 901, Neth. Appl, č. 6 605 956) se methamfetamin podrobí reakci s acetylenem v přítomnosti formaldehydu a chloridu měáného v dioxanu za zvýšené teploty v průběhu 30 h. Nevýhodou je velká náročnost postupu a riziko spojené s použitím acetylenu.Neth. Appl, No. 6,605,956), methamphetamine is reacted with acetylene in the presence of formaldehyde and cuprous chloride in dioxane at elevated temperature for 30 h. The disadvantage is the high process complexity and the risk associated with the use of acetylene.
Podle dalšího postupu-(Britský patent č. 1 031 425 a NSR patent č. 1 227 447) se N-methylpropargylamin alkyluje l-fenyl-2-chlorpropanem. V tomto případě nevýhoda postupu spočívá v nízkých výtěžcích a vysoké ceně výchozího aminu.According to a further procedure (British Patent No. 1,031,425 and German Patent No. 1,227,447), N-methylpropargylamine is alkylated with 1-phenyl-2-chloropropane. In this case, the disadvantage of the process lies in the low yields and high cost of the starting amine.
Podle dalšího postupu se selegilin vyrábí alkylací methamfetaminu propargylbromidem za vysokých teplot v toluenu (Neth. Appl. č. 6 605 956, US patent č. 3 496 195, Britský patent č. 1 031 425 a Rakouský patent č. 271 437) nebo v toluenu v přítomnosti lithium-amidu (švýcarský patent č. 393 306) nebo v dvojfázové směsi benzenu a vodného roztoku hydroxidu sodného při teplotě kolem 65 °C (Evropský patent č. 99 302, MaSarský patent č. 35 630). Společnou nevýhodou v .těchto postupech je technologická náročnost spojená s prací za vysokých teplot a zvláště thermická nestálost - polymerizace propargylbromidu, zvláště v přítomnosti silných basí, Selegilin se převádí na sůl vzorce I působením chlorovodíku v ethanolu (Rakouský patent č, 271 437) nebo ve směsi benzenu a ethanolu (Evropský patent Č. 99 302), nebo v etheru (Powler J. S.t J. Org. Chem. 42, 2637 (1977)).According to another method, selegiline is produced by alkylating methamphetamine with propargyl bromide at high temperatures in toluene (Neth. Appl. No. 6,605,956, U.S. Patent No. 3,496,195, British Patent No. 1,031,425 and Austrian Patent No. 271,437) or in toluene in the presence of lithium amide (Swiss Patent No. 393,306) or in a biphasic mixture of benzene and aqueous sodium hydroxide solution at a temperature of about 65 ° C (European Patent No. 99,302, Hungarian Patent No. 35,630). A common disadvantage in these processes is the technological complexity associated with high temperature work and, in particular, the thermal instability - polymerization of propargyl bromide, especially in the presence of strong bases. Selegiline is converted to the salt of formula I by treatment with hydrogen chloride in ethanol (Austrian Patent No. 271 437). a mixture of benzene and ethanol (European Patent No. 99,302), or in ether (Powler JSt J. Org. Chem. 42, 2637 (1977)).
Podstata způsobu výroby podle vynálezu spočívá vtom, že se l-fenyl-2-methylaminopropan vzorce IIThe process according to the invention is characterized in that 1-phenyl-2-methylaminopropane of the formula II is used
CaHc-CHo-CH-NHCH,C and Hc-CH o -CH-NHCH,
5 2 | 3 (H) 5 2 | 3 (H)
CH^ nechá reagovat s propargyloxy-trifenylfosfonium chloridem v množství minimálně 1 ekvivalentu, v přítomnosti triethylaminu, v polárním organickém rozpouštědle, např. v dimethylformamidu nebo acetonitrilu, v rozmezí teplot 5 až 60 °C, a potom s chlorovodíkem v isopropylalkoholu.CH 2 is reacted with propargyloxy-triphenylphosphonium chloride in an amount of at least 1 equivalent, in the presence of triethylamine, in a polar organic solvent such as dimethylformamide or acetonitrile, at temperatures ranging from 5 to 60 ° C, and then with hydrogen chloride in isopropanol.
Propargyloxy-trifenylfosfonium chlorid, který je vlastním alkylačním činidlem, vzniká in šitu působením propargylalkoholu na produkt reakce tetrachlormethanu sPropargyloxy-triphenylphosphonium chloride, which is the actual alkylating agent, is formed in situ by the action of propargyl alcohol on the reaction product of carbon tetrachloride with
4· ¥4 · ¥
CS 272 574 Bl trifenylfosfinem. Jeho reakcí s aminem vzorce II vzniká trifenylfosfinoxid, který je možno způsoby známými z literatury převést zpětně na výchozí fosfin, Celý postup je tedy formálně alkylaoí aminu vzorce II propargylalkoholem.CS 272 574 B1 with triphenylphosphine. Its reaction with an amine of formula II produces a triphenylphosphine oxide which can be converted back to the starting phosphine by methods known in the literature. Thus, the process is formally an alkylalamine of the amine of formula II with propargyl alcohol.
Reakce probíhá stejně dobře s racemickýni i opticky.aktivním aminem vzorce II.The reaction proceeds equally well with the racemic and optically active amine of formula II.
Zjistili jsme, že sůl vzorce I je možno vyrábět za mírných podmínek a ve vysoké čistotě postupem, který nevyžaduje použití silně dráždivého a při práci nebezpečného propargylbromidu.We have found that the salt of formula I can be produced under mild conditions and in high purity by a process that does not require the use of highly irritating and hazardous to propargyl bromide.
Následující příklady objasňují, avšak nikterak neomezují obecnost způsobu výroby podle vynálezu.The following examples illustrate but do not limit the generality of the inventive process.
Příklad 1Example 1
Směe 14,9 g (0,1 mol) (R)-(-)-desoxyefedrinu vzorce II, 6,2 g (0,11 mol) propargylalkoholu, 28,85 g (0,11 mol) trifenylfosfinu, 11,6 ml (0,12 mol) tetrachlormethanu, a 16,7 ml (0,12 mol) triethylaminu v 80 ml acetonitrilu se míchá při 25 °C po dobu 10 h a odpaří se ve vakuu vodní vývěvy. Odparek se opakovaně rozmíchá s toluenem (ICO a 2 x 40 ml), oddělené toluenové fáze se spojí, promyjí vodou (30 ml) a extrahují 2 x zředěnou kyselinou chlorovodíkovou (100 a 30 ml). Spoj.ené kyselé výtřepy se extrahují 30 ml toluenu, potom se zalkalizují konc. amoniakem (pH cca 9) a vyloučená base se vyjme do toluenu (70 a 30 ml). Spojené výtřepy se odpaří ve vakuu a odparek se rozpustí v 20 ml isopropylalkoholu. Do roztoku se za chlazení a míchání uvádí plynný chlorovodík do pH cca 3, a potom se přidá 0,05 g karborafinu. Po krátkém povaření a filtraci se roztok nechá krystalovat nejprve při teplotě 25 °C (eventuálně se naočkuje) a potom 10 h při 5 °C. Vyloučená sůl se odsaje a promyje 5 ml isopropylalkoholu a rekrystaluje se opět z isopropylalkoholu. Získá se 8,2 g, tj. 36,7 % hydrochloridů (R)-(A-selegilinu vzorce I. Sůl má teplotu tání 139,5 až 141 °C a specifickou otáčivost ///^-11,98° (c 6.4; voda).A mixture of 14.9 g (0.1 mol) of (R) - (-) - desoxyephedrine of formula II, 6.2 g (0.11 mol) of propargyl alcohol, 28.85 g (0.11 mol) of triphenylphosphine, 11.6 ml (0.12 mol) of carbon tetrachloride, and 16.7 ml (0.12 mol) of triethylamine in 80 ml of acetonitrile are stirred at 25 ° C for 10 h and evaporated in a water-jet vacuum. The residue was repeatedly stirred with toluene (10CO and 2 x 40 mL), the combined toluene phases were combined, washed with water (30 mL), and extracted twice with dilute hydrochloric acid (100 and 30 mL). The combined acidic shakes were extracted with 30 ml of toluene, then basified with conc. ammonia (pH ca. 9) and the precipitated base was taken up in toluene (70 and 30 ml). The combined shakes were evaporated in vacuo and the residue was dissolved in 20 ml of isopropyl alcohol. Hydrogen chloride gas is added to the solution while cooling and stirring to a pH of about 3, and then 0.05 g of carboraffin is added. After brief boiling and filtration, the solution is first crystallized at 25 ° C (eventually seeded) and then at 5 ° C for 10 h. The precipitated salt is filtered off with suction and washed with 5 ml of isopropanol and recrystallized again from isopropanol. 8.2 g (36.7%) of (R) - (A-selegiline hydrochloride of formula I) are obtained. The salt has a melting point of 139.5-141 ° C and a specific rotation of .alpha. 6.4; water).
Příklad 2Example 2
Směs 14,9 g (0,1 mol) (S)-(+)-desoxyefedrinu vzorce II, 5,61 g (0,1 mol) propargylalkoholu, 26,23 g (0,1 mol) trifenylfosfinu, 15,4 g (0,1 mol) tetrachlormethanu a 10,3 (0,1 mol) triethylaminu v 70 ml dimethylformamidu se míchá při 60 °C po dobu 4 h. K reakční směsi se přidá 200 ml benzenu a 100 ml vody a promíchá se. Organické fáze se oddělí, promyje ještě 2 χ 40 ml vody a dále zpracuje postupem podle příkladu 1. Získá se 7,8 g (34,8%) hydrochloridů (S)-(+)-selegilinu vzorce I, který má t. t. 138,5 až 141 °C a otáčivost /(//p2 + 12° (c 6.5; voda).A mixture of 14.9 g (0.1 mol) of (S) - (+) - desoxyephedrine of formula II, 5.61 g (0.1 mol) of propargyl alcohol, 26.23 g (0.1 mol) of triphenylphosphine, 15.4 g (0.1 mol) of carbon tetrachloride and 10.3 (0.1 mol) of triethylamine in 70 ml of dimethylformamide are stirred at 60 DEG C. for 4 hours. 200 ml of benzene and 100 ml of water are added to the reaction mixture and mixed. The organic phases are separated, washed with a further 2 ml of 40 ml of water and further treated as in Example 1. 7.8 g (34.8%) of (S) - (+) - selegiline hydrochloride of formula I are obtained, m.p. 5-141 ° C and a rotation / (// p 2 + 12 ° (c 6.5, H₂O).
Příklad 3Example 3
Postupem podle příkladu 1, s tím rozdílem, že se reakce provádí při teplotě +5 °C (cca 24 až 30 h), a k rekrystalizaci soli se použije acetonu místo isopropylalkoholu, se z (+)-de-soxyefedrinu vzorce II připraví hydrochlorid (+)-selegilinu(I) ve výtěžku 34,1 %. Teplota tání leží v rozmezí 129,5 až 132 °C.Using the procedure of Example 1, except that the reaction is carried out at a temperature of + 5 ° C (about 24 to 30 h) and to recrystallize the salt using acetone instead of isopropyl alcohol, the hydrochloride is prepared from (+) - de-soxyephedrine II. +) - selegiline (I) in 34.1% yield. Melting point: 129.5 - 132 ° C.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS370888A CS272574B1 (en) | 1988-05-30 | 1988-05-30 | Method of selegiline hydrochloride production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS370888A CS272574B1 (en) | 1988-05-30 | 1988-05-30 | Method of selegiline hydrochloride production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS370888A1 CS370888A1 (en) | 1990-05-14 |
| CS272574B1 true CS272574B1 (en) | 1991-02-12 |
Family
ID=5377925
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS370888A CS272574B1 (en) | 1988-05-30 | 1988-05-30 | Method of selegiline hydrochloride production |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS272574B1 (en) |
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1988
- 1988-05-30 CS CS370888A patent/CS272574B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS370888A1 (en) | 1990-05-14 |
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