CN102617455B - Preparation method of pyridoxal or pyridoxal hydrochloride - Google Patents

Preparation method of pyridoxal or pyridoxal hydrochloride Download PDF

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CN102617455B
CN102617455B CN201110442237.1A CN201110442237A CN102617455B CN 102617455 B CN102617455 B CN 102617455B CN 201110442237 A CN201110442237 A CN 201110442237A CN 102617455 B CN102617455 B CN 102617455B
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pyridoxal
hydrochloride
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pyridoxine
oxygen
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CN102617455A (en
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施湘君
苏为科
陈巧巧
章根宝
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Jiangxi Tianxin Pharmaceutical Ltd By Share Ltd
Zhejiang University of Technology ZJUT
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ZHEJIANG TIANXIN PHARMACEUTICAL CO Ltd
Zhejiang University of Technology ZJUT
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Abstract

The invention discloses a preparation method of pyridoxal or pyridoxal hydrochloride. The preparation method comprises: taking pyridoxine or pyridoxine hydrochloride shown in formula (III) as the starting material and water as the reaction solvent, conducting selective oxidation on the pyridoxine or pyridoxine hydrochloride in water under the effect of a catalytic oxidation system, thus obtaining the pyridoxal or pyridoxal hydrochloride shown in formula (I). The catalytic oxidation system includes an oxygen source, a catalyst, an inorganic salt and an amine ligand. The preparation method of the invention has the advantages of high conversion rate, good selectivity, mild reaction condition, easy operation, low cost, and environmental friendliness, thus boasting good industrial application value.

Description

The preparation method of a kind of pyridoxal or pyridoxal hydrochloride
(1) technical field
The present invention relates to the preparation method of a kind of pyridoxal or pyridoxal hydrochloride, especially a kind of selective oxidation pyridoxol or pyridoxine hydrochloride are prepared the method for pyridoxal or pyridoxal hydrochloride.
(2) background technology
Pyridoxal hydrochloride is vitamins B 6a kind of derivative, as shown in formula I, be the key intermediate of synthetic PLP.PLP chemistry PLP by name, is called for short PLP, is vitamins B 6a kind of activeconstituents forming under the kinase whose effect of Triphosaden in cell, structural formula is as formula II:
Figure BDA0000124941240000011
PLP is as a coenzyme, can from more than 100 different enzyme effects in body, the biochemistry of joint effect cells in vivo is movable and metabolic.It is to maintain the normal requisite material of human immune system; Be people's bulk-growth, grow, maintain the indispensable material of balance; It is the coenzyme of liver starch Phosphation.In addition, PLP, as a coenzyme, also can be assisted the synthetic of the interior nerve amines of brain cell, accelerates the recovery of impaired brain; In auxiliary nervous system, the myelin of nerve fiber forms; Helper folic acid metabolism etc.
The following several method of bibliographical information synthesizes pyridoxal:
Method one, Ahens H; Korytnyk W. (J.Heterocycl.Chem.Vol.4,1967:625-626) reported taking pyridoxine hydrochloride as starting raw material, obtains pyridoxal, yield 77% with Manganse Dioxide selective oxidation.Method two, More Ashok. (Spectrochimica Acta Part A.Vol.72,2009:204-208) has reported with H 2o 2for oxygenant, dichloro three (triphenyl phosphorus) ruthenium mixture is that catalyst selectivity oxidation pyridoxol is pyridoxal, yield 96.66%.
Above-mentioned two kinds of methods all have weak point, and it is oxygenant that first method is used Manganse Dioxide, produces a large amount of Mn-bearing waste waters, and difficult treatment is unfriendly to environment; The second weak point is used transition metal Ru, expensive, there is no at present industrial applications and is worth, and needs further exploitation of investigators.
(3) summary of the invention
Pollute the shortcomings such as large, process is complicated for overcoming in prior art reaction, the object of this invention is to provide that a kind of transformation efficiency is high, selectivity good, reaction conditions is gentle, easy to operate, with low cost, environmentally friendly, there is the method that selective oxidation pyridoxol that good industrial applications is worth or pyridoxine hydrochloride are prepared pyridoxal or pyridoxal hydrochloride.
For achieving the above object, the present invention adopts following technical scheme:
The preparation method of a kind of pyridoxal or pyridoxal hydrochloride, described preparation method comprises: taking the pyridoxol shown in formula III or pyridoxine hydrochloride as initial feed, taking water as reaction solvent, described pyridoxol or pyridoxine hydrochloride in water under the effect of catalytic oxidation system selective oxidation make the pyridoxal shown in formula I or pyridoxal hydrochloride;
Figure BDA0000124941240000021
Described catalytic oxidation system comprises oxygen source, catalyzer, inorganic salt and amine part;
It is one of following that described oxygen source is selected from: air, oxygen, hydrogen peroxide;
Described catalyzer is selected from following a kind of or several combination arbitrarily: 2,2,6,6-tetramethyl piperidine-nitrogen-oxyradical, 4-hydroxyl-2,2,6,6-tetramethyl piperidine-1-oxyradical, 4-acetylaminohydroxyphenylarsonic acid 2,2,6,6-tetramethyl piperidine-1-nitroxyl free radical, 4-amino-2,2,6,6-tetramethyl piperidine-1-oxyradical;
Described inorganic salt are selected from following a kind of or several combination arbitrarily: cupric nitrate, copper sulfate, copper trifluoromethanesulfcomposite, cupric sulfide, neutralized verdigris, cupric bromide, cuprous bromide, cupric iodide, cuprous iodide, cupric chloride, cuprous chloride;
Described amine part is selected from following a kind of or several combination arbitrarily: 1，2-diaminoethane, TERTIARY BUTYL AMINE, diethylamine, triethylamine, tri-tert amine, tri-n-butylamine, 1,4-diazabicylo [2.2.2] octane, morpholine, pyridine, PA, DMAP, 4,6-dimethyl-2-pyridine amine, ammoniacal liquor, ammonium chloride, ammonium sulfate, volatile salt, bicarbonate of ammonia, 2,2 '-dipyridyl, 4-isopropyl pyridine, 4-pyridone.
The present invention is in reaction process, and pyridoxal and pyridoxal hydrochloride, in chemical equilibrium, are exactly to prepare pyridoxal therefore prepare pyridoxal hydrochloride actual.
In the present invention, described selective oxidation carries out under the effect of catalytic oxidation system, and described catalytic oxidation system is preferably made up of oxygen source, catalyzer, inorganic salt and amine part.
In the present invention, in the time that described oxygen source is air or oxygen, the pressure of described air or oxygen is 1～5 normal atmosphere, is preferably 1～2 normal atmosphere.In the time that described oxygen source is hydrogen peroxide, the consumption of described hydrogen peroxide is with H 2o 2mole number count 0.5～8 times of mole number of pyridoxol or pyridoxine hydrochloride, be preferably 1～2 times.
Catalyzer of the present invention is nitroxyl free radical, and the consumption of described catalyzer is counted 0.01～5 times of mole number of pyridoxol or pyridoxine hydrochloride with mole number, be preferably 0.05～3 times.
Inorganic salt of the present invention are mantoquita or cuprous salt, and preferably inorganic salt are one of following: cupric bromide, cupric iodide, cupric chloride, cupric nitrate.In the present invention, the consumption of described inorganic salt is counted 0.01～3 times of mole number of pyridoxol or pyridoxine hydrochloride with mole number, be preferably 0.01～1 times, more preferably 0.01～0.5 times.
Amine part of the present invention is preferably from one of following: DMAP, 4-pyridone, ammoniacal liquor, ammonium chloride, triethylamine.In the present invention, the consumption of described amine part is counted 0.01～5 times of mole number of pyridoxol or pyridoxine hydrochloride with mole number, be preferably 0.01～1 times.
In the present invention, described selective oxidation carries out under the temperature condition of 0～55 DEG C.Preferably, described selective oxidation carries out under the temperature condition of 10～30 DEG C.
The present invention can adopt ordinary method (such as liquid chromatography) monitoring reaction end, and the general reaction times is at 1～2h.
The present invention, after selective oxidation completes, can obtain pyridoxal or pyridoxal hydrochloride by column chromatography.But due to pyridoxal and pyridoxal hydrochloride unstable, difficult separation, therefore in actual applications, after selective oxidation completes, gained reaction solution adds p-ethoxyaniline reaction without separation, obtain corresponding Schiff alkali (IX), this Schiff alkali stable in properties, can supply subsequent reactions.Concrete operations can be investigated the paper ANew Synthesis of Pyridoxal-5-phosphate that Masaru Iwanami delivers, Vol.41,1968:161-165.
Figure BDA0000124941240000041
Compared with prior art, the method for preparing pyridoxal or pyridoxal hydrochloride of the present invention has following advantage: transformation efficiency is high, and selectivity is good, and reaction conditions gentleness is easy to operate, with low cost, environmentally friendly, has good industrial applications and is worth.
(4) embodiment
With specific embodiment, technical scheme of the present invention is described below, but protection scope of the present invention is not limited to this:
Embodiment 1
In the 25mL reaction flask with agitator and thermometer, add successively 0.085g (0.5mmol) 2,2,6,6-tetramethyl piperidine-nitrogen-oxyradical, 0.29g (2mmol) cupric bromide, 0.40g (5mmol) pyridine and 2.06g (10mmol) pyridoxine hydrochloride.Add water 5mL, temperature is controlled at 30 DEG C, opens and stirs.Then drip 2.0g (18mmol) 30% hydrogen peroxide, control temperature of reaction at 30～35 DEG C simultaneously.After dropwising, insulation continues to stir 1～2 hour at 30～35 DEG C, and gained reaction solution reaches 99% (liquid-phase condition: chromatographic column is XDB-G8 250 × 4.6mm 5um through Liquid Detection pyridoxol transformation efficiency.Moving phase is methyl alcohol: buffer=15: 85; Buffer:0.04% sodium pentanesulfonate is adjusted PH to 3 with Glacial acetic acid; Detection wavelength is 284nm), reaction preference is 98%.
In addition, get about 5mL reaction solution and directly go up silicagel column, eluent is methylene dichloride: methyl alcohol=20: 1, obtain final elutriant through gradient elution, and be concentrated into dryly, can obtain white solid pyridoxal hydrochloride, fusing point 164.1-164.8 DEG C, nuclear-magnetism characterizes as follows: 1hNMR (400MHz, DMSO), δ: 8.27 (s, 1H, CHO), 6.63 (d, 1H, CH), 5.00-5.16 (m, 2H, CH 2), 2.62 (s, 3H, CH 3).
Because pyridoxal hydrochloride is unstable, difficult separation, investigate in actual applications paper [the A New Synthesis of Pyridoxal-5-phosphate that Masaru Iwanami delivers, Vol.41,1968:161-165], reaction solution then adds p-ethoxyaniline 1.37g (10mmol), treated yellow Schiff alkali (IX) 2.10g that obtains without separating.The total recovery of two-step reaction is 88%.
Embodiment 2
Oxygen source changes 1 atmospheric oxygen into, and inorganic salt change 1.5g (10mmol) cupric nitrate into, and amine part changes 1.0g (10mmol) triethylamine into, and other operate with embodiment 1, obtain yellow solid 2.21g.Liquid Detection pyridoxol transformation efficiency reaches 99%, and reaction preference is 97%.The total recovery of two-step reaction is 89%.
Embodiment 3
Oxygen source changes 2 atmospheric oxygen into, and inorganic salt change 0.29g (2mmol) cuprous bromide into, and amine part changes 0.24g (4mmol) 1，2-diaminoethane into, and other operate with embodiment 1, obtain yellow solid 1.90g.Liquid Detection pyridoxol transformation efficiency reaches 87%, and reaction preference is 95%.The total recovery of two-step reaction is 74%.
Embodiment 4
Catalyzer is changed to 0.17g (1mmol) 4-amino-2,2,6,6-tetramethyl piperidine-1-oxyradical, 30% hydrogen peroxide changes 0.55g (5mmol) into, and inorganic salt change 0.095g (0.5mmol) cupric iodide into, and amine part changes 0.24g (5mmol) 35% ammoniacal liquor into, other operate with embodiment 1, obtain yellow solid 2.07g.Liquid Detection pyridoxol transformation efficiency reaches 91%, and reaction preference is 95%.The total recovery of two-step reaction is 80%.
Embodiment 5
Catalyzer is changed to 0.09g (0.5mmol) 4-amino-2,2,6,6-tetramethyl piperidine-1-oxyradical, 30% hydrogen peroxide changes 2.8g (25mmol) into, and inorganic salt change 0.20g (2mmol) cupric chloride into, and amine part changes 1.4g (16mmol) morpholine into, other operate with embodiment 1, obtain yellow solid 2.29g.Liquid Detection pyridoxol transformation efficiency reaches 98%, and reaction preference is 96%.The total recovery of two-step reaction is 86%.
Embodiment 6
Catalyzer is changed to 0.086g (0.5mmol) 4-hydroxyl-2,2,6,6-tetramethyl piperidine-1-oxyradical, oxygen source changes an atmospheric air into, and inorganic salt change 1.0 (5mmol) neutralized verdigris into, amine part changes 1.3g (7mmol) tri-n-butylamine into, temperature of reaction changes 0～5 DEG C into, and other operate with embodiment 1, obtain yellow solid 1.93g.Liquid Detection pyridoxol transformation efficiency reaches 85%, and reaction preference is 95%.The total recovery of two-step reaction is 72%.
Embodiment 7
Catalyzer is changed to 0.86g (5mmol) 4-hydroxyl-2,2,6,6-tetramethyl piperidine-1-oxyradical, 30% hydrogen peroxide changes 1.4g (12mmol) into, 0.15g (1mmol) cupric bromide, amine part is changed to 0.095 (1mmol) 4-pyridone, temperature of reaction changes 30～35 DEG C into, and other operate with embodiment 1, obtain yellow solid 2.05g.Liquid Detection pyridoxol transformation efficiency reaches 92%, and reaction preference is 96%.The total recovery of two-step reaction is 81%.
Embodiment 8
Catalyzer changes 0.16g (0.8mmol) 4-acetylaminohydroxyphenylarsonic acid 2 into, 2,6,6-tetramethyl piperidine-1-nitroxyl free radical, oxygen source changes 1 atmospheric oxygen into, and inorganic salt change 0.29g (2mmol) cupric nitrate into, and amine part is changed to 1.2g (12mmol) triethylamine, other operate with embodiment 1, obtain yellow solid 2.10g.Liquid Detection pyridoxol transformation efficiency reaches 99%, and reaction preference is 92%.The total recovery of two-step reaction is 84%.
Embodiment 9
Catalyzer changes 3.0g (15mmol) 4-acetylaminohydroxyphenylarsonic acid 2 into, 2,6,6-tetramethyl piperidine-1-nitroxyl free radical, 30% hydrogen peroxide changes 1.4g (12mmol) into, and inorganic salt change 2.6g (18mmol) cuprous bromide into, and amine part is changed to 0.98 (8mmol) DMAP, other operate with embodiment 1, obtain yellow solid 1.95g.Liquid Detection pyridoxol transformation efficiency reaches 86%, and reaction preference is 97%.The total recovery of two-step reaction is 75%.
Embodiment 10
Catalyzer is changed to 4.3g (25mmol) 2,2,6,6-tetramethyl piperidine-nitrogen-oxyradical, 30% hydrogen peroxide changes 2.3g (20mmol) into, and inorganic salt change 0.38g (2mmol) cupric iodide into, and amine part changes 0.009g (0.1mmol) morpholine into, other operate with embodiment 1, obtain yellow solid 2.05g.Liquid Detection pyridoxol transformation efficiency reaches 93%, and reaction preference is 99%.The total recovery of two-step reaction is 85%.
Embodiment 11
Catalyzer is changed to 4.7g (30mmol) 2,2,6,6-tetramethyl piperidine-nitrogen-oxyradical, inorganic salt change 0.20g (2mmol) cupric chloride into, and amine part changes 1.9g (10mmol) tri-n-butylamine into, other operate with embodiment 1, obtain yellow solid 2.02g.Liquid Detection pyridoxol transformation efficiency reaches 90%, and reaction preference is 95%.The total recovery of two-step reaction is 76%.

Claims (9)

1.一种吡哆醛或盐酸吡哆醛的制备方法，所述制备方法包括：以式（Ⅲ）所示的吡哆醇或盐酸吡哆醇为初始原料，以水为反应溶剂，所述的吡哆醇或盐酸吡哆醇在水中在催化氧化体系的作用下选择性氧化制得式（Ⅰ）所示的吡哆醛或盐酸吡哆醛；所述的选择性氧化在0～55℃的温度条件下进行；1. a preparation method of pyridoxal or pyridoxal hydrochloride, said preparation method comprising: taking pyridoxine or pyridoxine hydrochloride shown in formula (Ⅲ) as initial raw material, taking water as reaction solvent, said Pyridoxine or pyridoxine hydrochloride are selectively oxidized in water under the action of a catalytic oxidation system to prepare pyridoxal or pyridoxal hydrochloride shown in formula (I); the selective oxidation is performed at 0-55°C under temperature conditions; 所述的催化氧化体系包括氧源、催化剂、无机盐和胺类配体；The catalytic oxidation system includes an oxygen source, a catalyst, an inorganic salt and an amine ligand; 所述的氧源选自下列之一：空气，氧气，双氧水；The oxygen source is selected from one of the following: air, oxygen, hydrogen peroxide; 所述的催化剂选自下列一种或任意几种的组合：2,2,6,6-四甲基哌啶-氮-氧自由基，4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基，4-乙酰氨基-2,2,6,6-四甲基哌啶-1-氮氧自由基，4-氨基-2,2,6,6-四甲基哌啶-1-氧自由基；The catalyst is selected from one or any combination of the following: 2,2,6,6-tetramethylpiperidine-nitrogen-oxygen free radical, 4-hydroxyl-2,2,6,6-tetramethyl Piperidin-1-oxyl radical, 4-acetamido-2,2,6,6-tetramethylpiperidin-1-nitroxyl radical, 4-amino-2,2,6,6-tetramethyl Piperidin-1-oxyl radical; 所述的无机盐选自下列一种或任意几种的组合：硝酸铜，硫酸铜，醋酸铜，溴化铜，溴化亚铜，碘化铜，碘化亚铜，氯化铜，氯化亚铜；The inorganic salt is selected from one or any combination of the following: copper nitrate, copper sulfate, copper acetate, copper bromide, cuprous bromide, copper iodide, cuprous iodide, cupric chloride, chlorinated Cuprous; 所述的胺类配体选自下列一种或任意几种的组合：1,2-乙二胺，叔丁胺，二乙胺，三乙胺，三叔丁基胺，三正丁胺，1,4-二氮杂二环[2.2.2]辛烷，吗啡啉，吡啶，2-氨基吡啶，4-二甲氨基吡啶，4,6-二甲基-2-吡啶胺，氨水，2,2'-联吡啶，4-异丙基吡啶，4-羟基吡啶。The amine ligand is selected from one or any combination of the following: 1,2-ethylenediamine, tert-butylamine, diethylamine, triethylamine, tri-tert-butylamine, tri-n-butylamine, 1, 4-diazabicyclo[2.2.2]octane, morpholine, pyridine, 2-aminopyridine, 4-dimethylaminopyridine, 4,6-dimethyl-2-pyridinamine, ammonia, 2,2 '-bipyridine, 4-isopropylpyridine, 4-hydroxypyridine. 2.如权利要求1所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述的选择性氧化在10～30℃的温度条件下进行。2. the preparation method of pyridoxal or pyridoxal hydrochloride as claimed in claim 1 is characterized in that: described selective oxidation is carried out under the temperature condition of 10～30 ℃. 3.如权利要求1所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述的催化氧化体系由氧源、催化剂、无机盐和胺类配体组成。3. the preparation method of pyridoxal or pyridoxal hydrochloride as claimed in claim 1 is characterized in that: described catalytic oxidation system is made up of oxygen source, catalyzer, inorganic salt and amine ligand. 4.如权利要求1～3之一所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述吡哆醇或盐酸吡哆醇与催化剂、无机盐、胺类配体的摩尔比为1：0.01～5：0.01～3：0.01～5；并且所述的氧源为空气或氧气，所述空气或氧气的压力为1～5个大气压，或者所述的氧源为双氧水，所述吡哆醇或盐酸吡哆醇与H2O2的摩尔比为1：0.5～8。4. the preparation method of pyridoxal or pyridoxal hydrochloride as described in one of claim 1～3, it is characterized in that: described pyridoxine or pyridoxine hydrochloride and catalyzer, inorganic salt, amine ligand The molar ratio is 1:0.01～5:0.01～3:0.01～5; and the oxygen source is air or oxygen, and the pressure of the air or oxygen is 1 to 5 atmospheres, or the oxygen source is hydrogen peroxide , the molar ratio of pyridoxine or pyridoxine hydrochloride to H2O2 is 1:0.5-8. 5.如权利要求4所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述吡哆醇或盐酸吡哆醇与催化剂、无机盐、胺类配体的摩尔比为1：0.05～3：0.01～1：0.01～1；并且所述的氧源为空气或氧气，所述空气或氧气的压力为1～2个大气压，或者所述的氧源为双氧水，所述吡哆醇或盐酸吡哆醇与H2O2的摩尔比为1：1～2。5. the preparation method of pyridoxal as claimed in claim 4 or pyridoxal hydrochloride is characterized in that: the mol ratio of described pyridoxine or pyridoxine hydrochloride and catalyzer, inorganic salt, amine ligand is 1 : 0.05～3: 0.01～1: 0.01～1; and the oxygen source is air or oxygen, and the pressure of the air or oxygen is 1 to 2 atmospheres, or the oxygen source is hydrogen peroxide, and the pyridine The molar ratio of pyridoxine or pyridoxine hydrochloride to H2O2 is 1:1~2. 6.如权利要求4所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述无机盐选自下列一种：溴化铜，碘化铜，氯化铜，硝酸铜。6. the preparation method of pyridoxal as claimed in claim 4 or pyridoxal hydrochloride is characterized in that: described inorganic salt is selected from following one: copper bromide, copper iodide, cupric chloride, cupric nitrate. 7.如权利要求5所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述无机盐选自下列一种：溴化铜，碘化铜，氯化铜，硝酸铜。7. the preparation method of pyridoxal as claimed in claim 5 or pyridoxal hydrochloride is characterized in that: described inorganic salt is selected from following one: copper bromide, copper iodide, cupric chloride, cupric nitrate. 8.如权利要求6或7所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述的胺类配体选自下列之一：4-二甲氨基吡啶，4-羟基吡啶，氨水，三乙胺。8. The preparation method of pyridoxal or pyridoxal hydrochloride as claimed in claim 6 or 7, is characterized in that: described amine ligand is selected from one of following: 4-dimethylaminopyridine, 4-hydroxyl Pyridine, ammonia, triethylamine. 9.如权利要求1所述的吡哆醛或盐酸吡哆醛的制备方法，其特征在于：所述制备方法还包括如下步骤：在选择性氧化完成后，所得反应液不经分离直接加入对乙氧基苯胺，反应得到式（Ⅸ）所示的Schiff碱，所述吡哆醛或盐酸吡哆醛以Schiff碱的形式保存，9. the preparation method of pyridoxal as claimed in claim 1 or pyridoxal hydrochloride is characterized in that: described preparation method also comprises the steps: after selective oxidation is finished, gained reaction solution directly adds to Ethoxyaniline, reaction obtains the Schiff base shown in formula (IX), and described pyridoxal or pyridoxal hydrochloride are preserved with the form of Schiff base,
Figure FDA0000460216460000021
Figure FDA0000460216460000021
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001072309A2 (en) * 2000-03-28 2001-10-04 Medicure International Inc. Treatment of cerebrovascular disease
WO2002004421A2 (en) * 2000-07-07 2002-01-17 Medicure International Inc. Pyridoxine and pyridoxal analogues: cardiovascular therapeutics
US6548519B1 (en) * 2001-07-06 2003-04-15 Medicure International Inc. Pyridoxine and pyridoxal analogues: novel uses
CN101628892A (en) * 2009-08-09 2010-01-20 常熟富士莱医药化工有限公司 Preparation method of pyridoxamine dihydrochloride

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001072309A2 (en) * 2000-03-28 2001-10-04 Medicure International Inc. Treatment of cerebrovascular disease
WO2002004421A2 (en) * 2000-07-07 2002-01-17 Medicure International Inc. Pyridoxine and pyridoxal analogues: cardiovascular therapeutics
US6548519B1 (en) * 2001-07-06 2003-04-15 Medicure International Inc. Pyridoxine and pyridoxal analogues: novel uses
CN101628892A (en) * 2009-08-09 2010-01-20 常熟富士莱医药化工有限公司 Preparation method of pyridoxamine dihydrochloride

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Ru(III)-catalyzed oxidation of pyridoxine and albuterol in pharmaceuticals;More Ashok，等;《Spectrochimica Acta Part A: Molecular andBiomolecular Spectroscopy》;20080803;第72卷(第1期);第204-208页 *
超声波催化二氧化锰氧化吡哆醇为吡哆醛的简便方法;何地平，等;《陕西师范大学学报自然科学版》;20040630;第32卷(第2期);第61-63页 *

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