- Preparation method of vinpocetine
-
The invention provides a preparation method of vinpocetine, which relates to the technical field of synthesis of medical intermediates, and comprises the following steps: (1) respectively feeding an ethanol solution of vincamine and an ethanol solution of sodium ethoxide into a premixer for premixing to form a mixed solution 1; (2) sending the mixed solution 1 obtained in the step (1) to a micro-channel module for complete reaction, and outputting the generated reaction solution to a transfer storage tank; (3) respectively feeding the solution and the mixed acid in the transfer storage tank obtained in the step (2) into a premixer for premixing to form a mixed solution 2; (4) sending the mixed solution 2 obtained in the step (3) to a micro-channel module for complete reaction, and outputting the generated reaction solution to a neutralization kettle; and (5) after the reaction is finished, carrying out post-treatment on the material in the neutralization kettle obtained in the step (4) to obtain the target product vinpocetine. The method has the advantages of high atom utilization rate, high selectivity, high yield and less solid waste, is beneficial to environmental protection, and is convenient for industrial production and utilization.
- -
-
Paragraph 0051; 0055-0058; 0061-0064; 0067-0070; 0073-0086
(2021/04/10)
-
- Method for preparing vinpocetine
-
The invention relates to a method for preparing a compound, specifically to a method for preparing vinpocetine. The method comprises the following steps: 1) preparation of a vinpocetine crude product, including, mixing an apovincamine ethanol solution and a sodium ethoxide ethanol solution for a reflux reaction, removing the solvent, adding ethanol, carrying out a reflux reaction of the sodium ethoxide ethanol solution, when the residual content of apovincamine is less than 0.3% of the added apovincamine raw material, performing hot filtration, removing a part of solvent of the filtered liquid, and performing cooling crystallization, solid-liquid separation, washing and drying to obtain the vinpocetine crude product; and 2) refining of vinpocetine, including adding active carbon, performing hot filtration, and performing recrystallization with ethanol for refining to obtain vinpocetine. The method is short and simple in process. The prepared vinpocetine is high in yield and purity, meets the standard of the European Pharmacopoeia (EP) 6.0, and is easy for industrial production.
- -
-
Paragraph 0018; 0141; 0147-0153
(2017/08/29)
-
- A semi-synthetic synthesis process of vinpocetine
-
The invention provides a vinpocetine semisynthesis process. The vinpocetine is obtained through hydrolysis, dehydration and esterification reactions by a one-pot method, and after the reactions are finished, extraction separation, purification and crystallization are performed, and finally, the high-content and high-purity product can be obtained. The method is few in reaction steps, simple in process flow, high in vinpocetine yield, simple in equipment, and green and environment-friendly in production procedure, and has tremendous economic and social benefits.
- -
-
Paragraph 0012; 0013
(2017/03/14)
-
- Process for the preparation of vinpocetine and apovincamine
-
A process for the preparation of vinpocetine and apovincamine, wherein said process comprises the steps of: (1) preparing a solution of the compound of formula (II) below and an organic or inorganic base in a polar aprotic solvent, and (2) adding an alkyl haloacetate to the solution of step (1) under controlled temperature conditions.
- -
-
Page/Page column 8
(2010/04/25)
-
- Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of pain, inflammation or inflammation mediated disorders
-
The present invention provides compositions and methods for the treatment of pain, inflammation or inflammation-mediated disorders in a subject. More particularly, the invention provides a combination therapy for the treatment of pain, inflammation or inflammation mediated disorders comprising the administration to a subject of a sodium ion channel blocker in combination with a cyclooxygenase-2 selective inhibitor.
- -
-
-
- APOVINCAMINIC ACID DERIVATIVE AND MEDICINE CONTAINING THE SAME
-
This invention relates to an apovincaminic acid derivative represented by the following formula (1): wherein R1represents a lower alkyl group, and R2represents an aryl group, which may be substituted by 1 to 5 substituents selected from halogen atoms and lower alkyl, lower alkoxy, lower alkoxycarbonyl, acylamino and nitro groups, a benzyl group, a quinolyl group or a thienyl group, or an acid addition salt thereof; and also to a drug containing the same. This compound has excellent vasodilating activity and platelet aggregation inhibiting activity, and can be used for the treatment of cerebrovascular disorder, thromboembolism and chronic arterial occlusive diseases and also for the improvement of blood flow disturbances.
- -
-
-
- A facile one-pot synthesis of vinpocetine
-
A one-pot synthesis of vinpocetine from vincamine was established. Lewis acids caused transesterification and/or dehydration of vincamine in EtOH. FeCl3 catalyzed both transesterification and dehydration while Ti(OEt)4 selectively catalyzed transesterification.
- Kuge,Nakazawa,Kometani,Sugaya,Mochida,Tomioka
-
p. 759 - 766
(2007/10/02)
-
- Syntheses and Cardiovascular Activity of Stereoisomers and Derivatives of Eburnane Alkaloids
-
The synthesis of all the possible isomers of the eburnamenine-vincamine type alkaloids 1b, 2a*, 3a and derivatives 4, 8, 9, 10 is described.Structures were determined by 1H- and 13C-NMR spectroscopy including special techniques such as DR, DEPT, DNOE, and 2D-HSC.In contrast to the known cerebrovascular effects of cis-(3S,16S) compounds, trans-(3S,16R) derivatives show a significant peripheral vasodilator effect. Key Word: Eburnanes / Alkaloids / Cardiovascular effects / Indoloquinolizines
- Czibula, Laszlo,Nemes, Andras,Visky, Gyoergy,Farkas, Maria,Szombathelyi, Zsolt,et al.
-
p. 221 - 230
(2007/10/02)
-
- Synthesis of vinca alkaloids and related compounds, XV. A new synthetic route to (+)-vincaminic and (+)-apovincaminic esters
-
Esters of types 7 and 8, possessing excellent vasodilating effects, have been prepared. A method has been found for the resolution of methyl ester 7c. A new method is described for the preparation of the lactam (+)-10 and its conversion to the oxime (+)-11, from which (+)-vincamine (1a) and the (+)-apovincaminic esters 2a,b were synthesized.
- Szabo,Kalaus,Szantay
-
p. 629 - 638
(2007/10/02)
-
- Synthesis of vinca alkaloids and related compounds. XVI. New route to the stereoselective synthesis of (+)-vincamine, (-)-vincamone and (+)-apovincaminic acid esters
-
A stereoselective methods has been elaborated for the synthesis of oxime esters, from which, as common intermediates, (+)-apovincaminic acid esters, (+)-vincamine and (-)-vincamone can be prepared.
- Szabo,Sapi,Kalaus,et al.
-
p. 3737 - 3747
(2007/10/02)
-
- Process for the synthesis of vincamine and related indole alkaloids
-
A process is taught for the synthesis of vincamine and related indole alkaloids, according to which, through only two steps and through a novel synthesis intermediate, namely the glycidic ester, having the formula STR1 wherein R represents --COOCH3 or --COOCH2 CH3, 1-ethyl-1,2,3,4,5,6,7,12b-octahydroindole[2,3-a]quinolizine-1-carboxaldehyde is reacted with a haloester in the presence of a base and the glycidic ester is converted to vincamine or apovincamine or like esters by reaction with a Lewis acid or a mineral acid, the reaction products being subsequently separated by chromatography.
- -
-
-
- Process for producing eburnane derivatives
-
A compound of the formula: STR1 wherein R1 is a C1 -C6 alkyl group and R is a hydrogen atom or a C1 -C6 alkyl group, and their salts, which are useful as cerebral vasodilator; and a compound of the formula: STR2 wherein R2 is a hydrogen atom or a C1 -C6 alkyl group, R3 is a hydrogen atom or the formula: --CO2 R1 (R1 is a C1 -C6 alkyl group) and W is an oxygen atom, an imino group or STR3 but not an imino group in case that R3 is a hydrogen atom, which are intermediates of the compound (I), useful per se as cerebral vasodilator and/or antihypertensive agents.
- -
-
-
- Synthesis of vincaminic acid derivatives
-
Vincaminic acid derivatives of formula (A) STR1 useful in treating cerebral insufficiency, are prepared by reacting 1-ethyl-2,3,4,6,7,12-hexahydroindolo[2,3-a]quinolizine with the 2,4-DNP hydrazone of ethyl or methyl bromopyruvate followed by (i) reduction of the C=N bond and (ii) simultaneous cyclization with removal of the ketone-protecting group in either order.
- -
-
-
- A NEW APPROACH TO (+/-)-APOVINCAMINE
-
A new approach to (+/-)-apovincamine, 2, is reported which bypasses the formation of (+/-)-vincamine, 1, and includes the dehydration of the β-hydroxy ester 7, obtained by regio-controlled alkylation of the stereochemically suitable aldehyde 6 with methyl chloroacetate.Using ethyl chloroacetate, the clinically useful apovincamine analogue, (+/-)-Cavinton, 3, is obtained. (+/-)-Apovincamine is then converted to (+/-)-vincamine, 1, by base-catalyzed oxygenation of the mixture of (+/-)-dihydroapovincamines 8 and 9.
- Danieli, Bruno,Lesma, Giordano,Palmisano, Giovanni
-
p. 257 - 268
(2007/10/02)
-
- Synthesis of Some Isotype Analogs of Vincamine, Eburnamonine and Eburnamine, and an Alternative Approach to Ethyl Apovincaminate
-
New synthetic analogs of Vinca minor alkaloids were described, together with a new total synthesis of ethyl apovincaminate.
- Ono, Keiichi,Kawakami, Hajime,Katsube, Junki
-
p. 411 - 414
(2007/10/02)
-
