LV15015B - Salt of 3-carboxy-4-(r)-phenylpyrrolidinone-2 and uses thereof - Google Patents
Salt of 3-carboxy-4-(r)-phenylpyrrolidinone-2 and uses thereof Download PDFInfo
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- LV15015B LV15015B LVP-13-209A LV130209A LV15015B LV 15015 B LV15015 B LV 15015B LV 130209 A LV130209 A LV 130209A LV 15015 B LV15015 B LV 15015B
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- Prior art keywords
- carboxy
- phenylpyrrolidin
- salt
- benzoyloxyquinuclidine
- water
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- 150000003839 salts Chemical class 0.000 title claims description 15
- 238000000034 method Methods 0.000 claims abstract description 12
- UOQRZCNCICUPJO-IENPIDJESA-N (4r)-2-oxo-4-phenylpyrrolidine-3-carboxylic acid Chemical compound C1NC(=O)C(C(=O)O)[C@@H]1C1=CC=CC=C1 UOQRZCNCICUPJO-IENPIDJESA-N 0.000 claims abstract description 7
- AHKAOMZZTQULDS-CYBMUJFWSA-N [(3s)-1-azabicyclo[2.2.2]octan-3-yl] benzoate Chemical compound O([C@H]1C2CCN(CC2)C1)C(=O)C1=CC=CC=C1 AHKAOMZZTQULDS-CYBMUJFWSA-N 0.000 claims abstract description 5
- UOQRZCNCICUPJO-UHFFFAOYSA-N 2-oxo-4-phenylpyrrolidine-3-carboxylic acid Chemical compound C1NC(=O)C(C(=O)O)C1C1=CC=CC=C1 UOQRZCNCICUPJO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 7
- WOICZUZBFJVANR-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-2-yl benzoate Chemical class C1C(CC2)CCN2C1OC(=O)C1=CC=CC=C1 WOICZUZBFJVANR-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- IVLICPVPXWEGCA-SSDOTTSWSA-N (3s)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@H](O)CN1CC2 IVLICPVPXWEGCA-SSDOTTSWSA-N 0.000 description 1
- -1 3-Carboxy-4- (3R) -phenylpyrrolidin-2-one Chemical compound 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229950006476 benzoclidine Drugs 0.000 description 1
- 238000006480 benzoylation reaction Methods 0.000 description 1
- 229940125693 central nervous system agent Drugs 0.000 description 1
- 239000003576 central nervous system agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
IZGUDROJUMA APRAKSTSDESCRIPTION OF THE INVENTION
Aprakstītais izgudrojums kopumā attiecas uz starpproduktiem medicīnisko preparātu iegūšanai, un īpaši uzjaunu procesu 3-karboksi-4-(7?)-fenilpirolidin-2-ona sintēzei.The present invention relates generally to intermediates for the preparation of medical preparations, and in particular to a novel process for the synthesis of 3-carboxy-4- (7R) -phenylpyrrolidin-2-one.
. Minētais 3-karboksi-4-(7?)-fenilpirolidin-2-ons dekarboksilēšanas ceļā viegli var tikt pārvērsts par zināmo 4-(7?)-fenilpirolidin-2-onu [Synthesis, 1023-1026 lpp. (1991)], noderīgu izejvielu N-karbamoilmetil-4-(Ā)-fenilpirolidin-2-ona sintēzei, kas ir zināms kā centrālās nervu sistēmas aģenta Karfedona (Caphedon, INN) aktīvais enantiomērs [W0/2007/l 04780],. Said 3-carboxy-4- (7R) -phenylpyrrolidin-2-one can readily be converted, via decarboxylation, to the known 4- (7R) -phenylpyrrolidin-2-one [Synthesis, pp. 1023-1026. (1991)], a useful starting material for the synthesis of N-carbamoylmethyl-4- (N) -phenylpyrrolidin-2-one known as the active enantiomer of the central nervous system agent Carfedon (Caphedon, INN) [WO / 2007 / l 04780],
Racemiskā 3-karboksi-4-fenilpirolidin-2-ona sadalīšanas metode frakcionēti kristalizējot 3karboksi-4-(R)-fenilpirolidin-2-ona cinhonidīna sāli ir jau zināma [Pol. J. Chem., 53, 435-446 lpp. (1979)]. Tomēr, šī metode nav piemērota pielietošanai rūpnieciskā mērogā, jo tajā tiek izmantots liels viegli uzliesmojošu šķīdinātāju daudzums, tā ir laika un resursu ietilpīga un dod zemus un nestabilus iznākumus.The racemic method of cleaving 3-carboxy-4-phenylpyrrolidin-2-one by fractional crystallization of the 3-carboxy-4- (R) -phenylpyrrolidin-2-one quinonidine salt is already known [Pol. J. Chem., 53, 435-446. (1979)]. However, this method is not suitable for use on an industrial scale because it uses a large amount of highly flammable solvents, is time and resource intensive and produces low and unstable results.
Ir zināma optiski aktīva šī preparāta enzimātiskā sintēze [Latv. Pat. LV13635 (2006)], taču šai metodei ir vairāki trūkumi, kā piemēram, tā ir dārga un nav pielietojama šīs vielas lielu apjomu ražošanā.Optically active enzymatic synthesis of this preparation is known [Latv. Pat. LV13635 (2006)], but this method has several disadvantages, such as being expensive and not applicable to the production of large quantities of this substance.
Ņemot vērā ka minētās metodes trūkumi nevar būt novērsti, būtu vēlams atrast jaunu pieejamu procesu, viegli pielietojamu rūpnieciskajos daudzumos, kam potenciāli var būt liels pozitīvais ekonomiskais efekts.Given that the drawbacks of this method cannot be eliminated, it would be desirable to find a new available process, readily applicable in industrial quantities, which can potentially have a large positive economic effect.
Negaidīti mēs atradām, ka 3-karboksi-4-(72)-fenilpirolidin-2-ons veido izteikti kristālisko sāli ar 3-(S)-benzoiloksihinuklidīnu, kura pielietošana enantiomēru atdalīšanā nav zināma. Minētais 3-(0)-benzoiloksihinuklidīns pieejams vai nu sadalot komerciāli pieejamā 3-(Ā,5)benzoiloksihinuklidīna (INN - Benzoclidine) enantiomērus, vai nu benzoilējot komerciāli pieejamo 3-(S)-hidroksihinuklidīnu, kā tas ir aprakstīts racemāta sintēzei [Bioorg. & Med. Chem. Lett., 14, 3781 - 3784 lpp.].Unexpectedly, we found that 3-carboxy-4- (72) -phenylpyrrolidin-2-one forms a highly crystalline salt of 3- (S) -benzoyloxyquinuclidine, the use of which in enantiomeric separation is unknown. Said 3- (O) -benzoyloxyquinuclidine is available either by cleavage of the enantiomers of commercially available 3- (α, 5) benzoyloxyquinuclidine (INN-Benzoclidine), or by benzoylation of commercially available 3- (S) -hydroxyquinuclidine as described for racemate synthesis [Bioorg . & Med. Chem. Lett., 14, pp. 3781-3784].
Saskaņā ar šo izgudrojumu, jauns izteikti kristālisks 3-karboksi-4-(7?)-fenilpirolidin-2-ona sāls ar 3-(5)-benzoiloksihinuklidīnu viegli var tikt iegūts izmantojot procesu, kas ir piemērots mēroga palielināšanai izmantošanai rūpniecībā. 3-Karboksi-4-(7?)-fenilpirolidin-2-ona sāls ar 32 (5)-benzoiloksihinuklidīnu tika iegūts ar augstu iznākumu un tīrību reaģējot racemiskajam 3karboksi-4-(7?yS)-fenilpirolidin-2-onam ar 3-(5)-benzoiloksihinuklidīnu šķīdinātājā, kam seko iegūtā tehniskā sāls pārkristalizēšana.According to the present invention, a novel crystalline 3-carboxy-4- (7R) -phenylpyrrolidin-2-one salt with 3- (5) benzoyloxyquinuclidine can be readily obtained by a process suitable for scale-up for industrial use. The 3-Carboxy-4- (7R) -phenylpyrrolidin-2-one salt with 32 (5) -benzoyloxyquinuclidine was prepared in high yield and purity by reaction of the racemic 3carboxy-4- (7S) -phenylpyrrolidin-2-one with 3 - (5) benzoyloxyquinuclidine in solvent followed by recrystallization of the resulting technical salt.
Labākajā piemērā, šķīdinātāji reakcijai un pārkristalizēšanai izvēlēti no grupas, kas ietver sevī, bet nav ierobežota ar ūdeni, metanolu, etanolu, propanolu-l, propanoIu-2 un acetonitrilu. Vislabākajā piemērā 3-karboksi-4-(7??S)-fenilpirolidin-2-ona reakcija ar 3-(5)benzoiloksihinuklidīnu ir veikta etanolā, un 3-karboksi-4-(Ā)-fenilpirolidin-2-ona sāls ar 3-(5)benzoiloksihinuklidīnu pārkristalizācija ir veikta no ūdens.In the best example, the reaction and recrystallization solvents are selected from the group consisting of, but not limited to, water, methanol, ethanol, propanol-1, propanol-2 and acetonitrile. Ideally example 3-carboxy-4- (7?? S) -fenilpirolidin-2-one with 3- (5) benzoiloksihinuklidīnu is carried out in ethanol, and 3-carboxy-4- (a) -fenilpirolidin-2-one salt of Recrystallization of 3- (5) benzoyloxyquinuclidines is from water.
Minētais sāls veido vēlamo 3-karboksi-4-(7?)-fenilpirolidin-2-onu protonēšanas laikā ar piemērotu minerālskābi ūdenī, vislabāk veicot protonēšanu ar sālsskābi. 3-Karboksi-4-(3?)fenilpirolidin-2-ons, kas kristalizējas no šķīduma, ir piemērots tālākai pielietošanai bez papildus attīrīšanas, bet var ari tikt pārkristalizēts no ūdens.Said salt forms the desired 3-carboxy-4- (7R) -phenylpyrrolidin-2-one during protonation with a suitable mineral acid in water, preferably by protonation with hydrochloric acid. 3-Carboxy-4- (3R) -phenylpyrrolidin-2-one, which crystallizes from solution, is suitable for further use without further purification, but can also be recrystallized from water.
Tātad, šis izgudrojums piedāvā jaunu ērtu metodi 3-karboksi-4-(/?)-fenilpiroIidin-2-ona ražošanai no racemāta, izmantojot jaunu sadalīšanas reaģentu rūpniecībā pieļaujamajos šķīdinātājos.Thus, the present invention provides a novel convenient method for the preparation of 3-carboxy-4- (R) -phenylpyrrolidin-2-one from a racemate using a novel cleavage reagent in industrially acceptable solvents.
Izgudrojuma sfēru neierobežo aprakstītie piemēri, kuriem ir demonstrējošs raksturs.The scope of the invention is not limited by the following examples which are illustrative.
PIEMĒRIEXAMPLES
Sekojošie piemēri ilustrē bet neierobežo doto izgudrojumu.The following examples illustrate but do not limit the invention.
Piemērs 1.Example 1.
3-Karboksi-4-(R)-fenilpirolidin-2-ona sāls ar 3-(S)-benzoiloksihinuklidīnu3-Carboxy-4- (R) -phenylpyrrolidin-2-one salt with 3- (S) -benzoyloxyquinuclidine
210 g 3-karboksi-4-(7?A)-fenilpirolidin-2-ona suspendē 570 ml etanola. Suspensiju uzsilda līdz apmēram 60 °C un, maisot, pievieno 240 g 3-(5)-benzoiloksihinuklidīna šķīdumu 240 ml etanola. Reakcijas maisījumu maisa pie šīs temperatūras apmēram 20 min, un tad ļauj atdzist līdz istabas temperatūrai. Kristāliskas nogulsnes filtrē un mazgā ar 300 ml etanola. Iegūto sāli žāvē, pēc tam izšķīdina 750 ml karstā ūdens, filtrē un ļauj kristalizēties istabas temperatūrā 2 stundu laikā. Kristāliskās nogulsnes nofiltrē, mazgā ar 200 ml ūdens un žāvē. Balta kristāliskā sāls iznākums 160 g. [a]D 20 (metanols, c = 2) = -55.7°; kuš. temp. 170-172 °C (sadal.).; C25H28N2O5, aprēķināts %: C 68.79; H 6.47; N 6.42, atrasts %: C 68.94; H 6.46; N 6.42.210 g of 3-carboxy-4- (7?) -Phenylpyrrolidin-2-one are suspended in 570 ml of ethanol. The suspension is heated to about 60 ° C and 240 g of a solution of 3- (5) benzoyloxyquinuclidine in 240 ml of ethanol are added with stirring. The reaction mixture is stirred at this temperature for about 20 min and then allowed to cool to room temperature. The crystalline precipitate is filtered off and washed with 300 ml of ethanol. The resulting salt is dried, then dissolved in 750 ml of hot water, filtered and allowed to crystallize at room temperature for 2 hours. The crystalline precipitate is filtered off, washed with 200 ml of water and dried. White crystalline salt yield 160 g. [α] D 20 (methanol, c = 2) = -55.7 °; kuš. temp. 170-172 ° C (dec.); For C25H28N2O5, calculated%: C 68.79; H, 6.47; N, 6.42. Found:% C, 68.94; H, 6.46; N, 6.42.
Piemērs 2.Example 2.
3-Karboksi-4-(7?)-fenilpirolidin-2-ona sāls ar 3-6S)-benzoiloksihinukIidīnu3-Carboxy-4- (7R) -phenylpyrrolidin-2-one salt with 3-6S) -benzoyloxyquinucidine
210 g 3-karboksi-4-(7?A)-fenilpirolidin-2-ona suspendē 520 ml acetonitriia. Suspensiju uzsilda līdz apmēram 60 °C un, maisot, pievieno 240 g 3-(S)-benzoiloksihinuklidīna šķīdumu 320 ml acetonitriia. Reakcijas maisījumu maisa pie šīs temperatūras apmēram 20 min, un tad ļauj atdzist līdz istabas temperatūrai. Kristāliskas nogulsnes nofiltrē un mazgā ar 170 ml acetonitriia. Iegūto sāli žāvē, pēc tam izšķīdina 750 ml karstā ūdens, filtrē un ļauj kristalizēties istabas temperatūrā 2 stundu laikā. Kristāliskās nogulsnes nofiltrē, mazgā ar 200 ml ūdens un žāvē. Balta kristāliskā sāls iznākums 152 g. [a]o20 (metanols, c = 2) = -56.2°; kuš. temp. 170172 °C (sadal.).210 g of 3-carboxy-4- (7?) -Phenylpyrrolidin-2-one are suspended in 520 ml of acetonitrile. The suspension is heated to about 60 ° C and 240 g of a solution of 3- (S) -benzoyloxyquinuclidine in 320 ml of acetonitrile are added with stirring. The reaction mixture is stirred at this temperature for about 20 min and then allowed to cool to room temperature. The crystalline precipitate is filtered off and washed with 170 ml of acetonitrile. The resulting salt is dried, then dissolved in 750 ml of hot water, filtered and allowed to crystallize at room temperature for 2 hours. The crystalline precipitate is filtered off, washed with 200 ml of water and dried. White crystalline salt 152 g. [α] D 20 (methanol, c = 2) = -56.2 °; kuš. temp. 170172 ° C (dec.).
Piemērs 3.Example 3.
3-Karboksi-4-(J?)-fenilpirolidin-2-ons3-Carboxy-4- (R) -phenylpyrrolidin-2-one
160 g 3-karboksi-4-(Ā)-fenilpirolidin-2-ona sāls ar 3-(S)-benzoiloksihinuklidīriu izšķīdina 700 ml ūdens pie 65 °C un pakāpeniski apstrādā ar 40 ml koncentrētās sālsskābes līdz pH <3. Novēro 3-karboksi-4-(7?)-fenilpirolidin-2-ona kristalizēšanos balto kristālu veidā. Reakcijas maisījumu atdzesē līdz istabas temperatūrai un atstāj uz 2 stundām. Nogulsnes nofiltrē, mazgā ar 200 ml ūdens istabas temperatūrā un žāvē vakuumā. Iegūst 70 g 3-karboksiA-(7?)-fenilpiroIidin-2ona balto kristālu veidā (iznākums no racemāta 34.3 %). Kuš. temp. 136.5 °C, [α]ο2θ (metanols, c = 2) = -138.6°.160 g of 3-carboxy-4- (N) -phenylpyrrolidin-2-one salt with 3- (S) -benzoyloxyquinuclide are dissolved in 700 ml of water at 65 ° C and gradually treated with 40 ml of concentrated hydrochloric acid to pH <3. Crystallization of 3-carboxy-4- (7R) -phenylpyrrolidin-2-one as white crystals is observed. The reaction mixture is cooled to room temperature and left for 2 hours. The precipitate is filtered off, washed with 200 ml of water at room temperature and vacuum dried. 70 g of white crystals of 3-carboxy-A- (7R) -phenylpyrrolidin-2-one are obtained (yield 34.3% from the racemate). Kush. temp. 136.5 ° C, [α] ο 2θ (methanol, c = 2) = -138.6 °.
Claims (4)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LVP-13-209A LV15015B (en) | 2013-12-13 | 2013-12-13 | Salt of 3-carboxy-4-(r)-phenylpyrrolidinone-2 and uses thereof |
| PCT/IB2014/066846 WO2015087291A1 (en) | 2013-12-13 | 2014-12-12 | 3-carboxy-4-(r)-phenylpyrrolydine-2-one salt and its use |
| EA201691190A EA027373B1 (en) | 2013-12-13 | 2014-12-12 | Method for separating racemic 3-carboxy-4-phenylpyrrolydine-2-one using 3-(s)-benzoyloxyquinuclidine |
| UAA201606170A UA114161C2 (en) | 2013-12-13 | 2014-12-12 | 3-CARBOXY-4- (R)-PHENYLPYROLIDINE-2-SALT SALT AND ITS USE |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LVP-13-209A LV15015B (en) | 2013-12-13 | 2013-12-13 | Salt of 3-carboxy-4-(r)-phenylpyrrolidinone-2 and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LV15015A LV15015A (en) | 2015-06-20 |
| LV15015B true LV15015B (en) | 2015-12-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| LVP-13-209A LV15015B (en) | 2013-12-13 | 2013-12-13 | Salt of 3-carboxy-4-(r)-phenylpyrrolidinone-2 and uses thereof |
Country Status (4)
| Country | Link |
|---|---|
| EA (1) | EA027373B1 (en) |
| LV (1) | LV15015B (en) |
| UA (1) | UA114161C2 (en) |
| WO (1) | WO2015087291A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LV13635B (en) | 2006-02-23 | 2008-01-20 | Olainfarm As | Enzymatic resolution of racemic 3-aryl-4-aminobutyric acids |
| LV13630B (en) | 2006-03-16 | 2007-12-20 | Olainfarm As | Method of preparation and use of pharmaceutically active n-carbamoylmethyl-4(r)-phenyl-2-pyrrolidinone |
-
2013
- 2013-12-13 LV LVP-13-209A patent/LV15015B/en unknown
-
2014
- 2014-12-12 EA EA201691190A patent/EA027373B1/en unknown
- 2014-12-12 WO PCT/IB2014/066846 patent/WO2015087291A1/en active Application Filing
- 2014-12-12 UA UAA201606170A patent/UA114161C2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| UA114161C2 (en) | 2017-04-25 |
| EA027373B1 (en) | 2017-07-31 |
| WO2015087291A1 (en) | 2015-06-18 |
| EA201691190A1 (en) | 2016-12-30 |
| LV15015A (en) | 2015-06-20 |
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