CN110054580A - The preparation method of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride - Google Patents
The preparation method of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride Download PDFInfo
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- CN110054580A CN110054580A CN201910426858.7A CN201910426858A CN110054580A CN 110054580 A CN110054580 A CN 110054580A CN 201910426858 A CN201910426858 A CN 201910426858A CN 110054580 A CN110054580 A CN 110054580A
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- Prior art keywords
- butyric acid
- acid hydrazides
- maleimide phenyl
- hydrochloride
- preparing
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
Abstract
The invention discloses a kind of processes for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride, include the following steps: Step 1: using 4- (4- aminophenyl) methyl butyrate as raw material, under the catalytic action of anhydride compound and organic solvent, intermediate is obtained with maleic acid anhydride reactant;Step 2: the intermediate obtained in step 1 is obtained 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride under the action of organic solvent with hydrochloric acid hydrazine reaction.The present invention has that easy to operate, reaction condition is mild, and the yield of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride is higher, and operation is easy, can sufficiently meet the beneficial effect of product ommercialization production requirement.
Description
Technical field
The invention belongs to a kind of protein cross agent preparation technical fields, and in particular to a kind of to prepare the 4- (Malaysia 4-N- acyl
Imines phenyl) butyric acid hydrazides hydrochloride process.
Background technique
Protein cross agent is small molecule compound, have 2 or more for specific groups (- NH2 ,-
COOH ,-HS etc.) reactive terminal, can be coupled respectively with 2 or more molecule, so that these molecules be made to be incorporated in
Together, conjugation albumen is ultimately formed.
Contain maleimide base group, Ke Yiyu in 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloric acid molecules of salt one end
It is coupled containing thiol protein, the other end contains diazanyl, can be coupled with the protein of base containing aldehyde ketone, is a kind of efficient
Heterobifunctional Reagent.
4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride has company at present and carries out commercialization offer, but temporarily
When there are no open source literatures to report its synthetic method.Therefore, it if domestic manufacturers attempt to go to be synthesized, will spend big
Amount time and efforts goes to grope its technique, and the uncertain tricks of the trade that can find out its synthetic method.
In order to solve the problems, such as that 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride cannot be effectively synthesized, one is found
Kind highway route design is reasonable, and the controllable 4- of cost (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride synthetic method has very
Important meaning.
In view of the above-mentioned process for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride there are costs not
Controllably, synthesis step needs such as grope at the technical problems.Therefore, there is an urgent need in the art to find, a kind of synthesis cycle is short, high income
And the industrialized preparing process of synthesis 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride that cost is controllable is with non-
Often important meaning.
Summary of the invention
It is an object of the present invention to provide a kind of technique for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
Method, be able to solve during the preparation process design route needs grope, the technical problem that cost is uncontrollable and yield is unknown.
In order to solve the above technical problems, the present invention provides and a kind of prepares 4- (4-N- maleimide phenyl) butyric acid hydrazides salt
The process of hydrochlorate, wherein include the following steps: Step 1: methyl butyrate is raw material using 4- (4- aminophenyl), in acid anhydrides
Under the catalytic action of class compound and organic solvent, intermediate is obtained with maleic acid anhydride reactant;
Step 2: the intermediate obtained in step 1 is obtained under the action of organic solvent with hydrochloric acid hydrazine reaction
4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride.
Preferably, the anhydride compound in step 1 is one of acetic anhydride, phthalic anhydride, succinic anhydride or more
Kind.
Preferably, the organic solvent in step 1 is methylene chloride, chloroform, acetonitrile, toluene, dimethylbenzene, tetrahydro furan
It mutters, one of 2- methyltetrahydrofuran, glycol dimethyl ether, ethylene glycol diethyl ether or diethylene glycol dimethyl ether or a variety of.
Preferably, the dosage of the maleic anhydride in step 1 is 0.5-5 equivalent.
Preferably, the dosage of the anhydride compound in step 1 is 1-10 equivalent.
Preferably, the range of reaction temperature of step 1 is -20~200 DEG C.
Preferably, the organic solvent in step 2 is methylene chloride, chloroform, acetonitrile, methanol, ethyl alcohol, acetone, acetic acid
Ethyl ester, butyl acetate, toluene, dimethylbenzene, tetrahydrofuran, 2- methyltetrahydrofuran, glycol dimethyl ether, ethylene glycol diethyl ether,
One of diethylene glycol dimethyl ether, 2- butanone or NMP or a variety of.
Preferably, the dosage of the hydrazine hydrochloride in step 2 are as follows: 0.5-10 equivalent.
Preferably, the range of reaction temperature of step 2 is -20~200 DEG C.
The process for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride of the invention is compared to existing
Technology has the advantages that
1, process reaction route of the present invention is short, it is only necessary to which the reaction of 2 steps can synthesize, i.e. operating process letter
Just, strong applicability.
2, process of the invention is easy to operate, reaction condition is mild, and 4- (4-N- maleimide phenyl) butyric acid
The yield of hydrazides hydrochloride is higher, and operation is easy, can sufficiently meet the needs of product ommercialization production.
Detailed description of the invention
It, below will be to example or existing skill in order to illustrate more clearly of example of the present invention or technical solution in the prior art
Attached drawing needed in art description is briefly described, it should be apparent that, the accompanying drawings in the following description is only the present invention
Some examples for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other attached drawings.
Fig. 1 is the process of the process for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride of the invention
Structural schematic diagram.
Specific embodiment
To keep the objectives, technical solutions, and advantages of the present invention more clear, With reference to embodiment and join
According to attached drawing, the present invention is described in more detail.It should be understood that these descriptions are merely illustrative, and it is not intended to limit this hair
Bright range.In addition, in the following description, the description to known features and technology is omitted, to avoid this is unnecessarily obscured
The concept of invention.
Fig. 1 is the process of the process for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride of the invention
Structural schematic diagram, as shown in Figure 1, preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride the present invention provides a kind of
Process, wherein include the following steps:
Step 1: using 4- (4- aminophenyl) methyl butyrate as raw material, in the catalysis of anhydride compound and organic solvent
Under effect, intermediate is obtained with maleic acid anhydride reactant;
Step 2: the intermediate obtained in step 1 is obtained under the action of organic solvent with hydrochloric acid hydrazine reaction
4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride.
In further embodiment of the present invention, the anhydride compound in step 1 is acetic anhydride, phthalic anhydride, succinic anhydride
One of or it is a variety of.
In further embodiment of the present invention, organic solvent in step 1 be methylene chloride, chloroform, acetonitrile, toluene,
In dimethylbenzene, tetrahydrofuran, 2- methyltetrahydrofuran, glycol dimethyl ether, ethylene glycol diethyl ether or diethylene glycol dimethyl ether
It is one or more.
In further embodiment of the present invention, the dosage of the maleic anhydride in step 1 is 0.5-5 equivalent, step
The dosage of anhydride compound in one is 1-10 equivalent.It is reacted using above-mentioned dosage, not only reaction is mild, and obtains
Reaction product yield it is higher.
In further embodiment of the present invention, organic solvent in step 2 be methylene chloride, chloroform, acetonitrile, methanol,
Ethyl alcohol, acetone, ethyl acetate, butyl acetate, toluene, dimethylbenzene, tetrahydrofuran, 2- methyltetrahydrofuran, glycol dimethyl ether,
One of ethylene glycol diethyl ether, diethylene glycol dimethyl ether, 2- butanone or NMP or a variety of.
In further embodiment of the present invention, the dosage of the hydrazine hydrochloride in step 2 are as follows: 0.5-10 equivalent, using the use
Amount is reacted with intermediate, and not only reaction is mild, and its reaction product yield obtained is higher.
In further embodiment of the present invention, the range of reaction temperature of step 1 is -20~200 DEG C, step 2 it is anti-
Answering temperature range is -20~200 DEG C.The reaction yield carried out under the conditions of the reaction temperature is higher, and the reaction time is faster.
Below in conjunction with specific example, the present invention will be further described, certain specific example be for illustrate the present invention without
It is for limiting the scope of the invention.
Example 1 prepares the process of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
This example is to prepare the process of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride, including walk as follows
It is rapid:
Step 1: the preparation of intermediate
500mL toluene, 193g 4- (4- aminophenyl) methyl butyrate, 105g maleic are sequentially added into 2L reaction flask
Dicarboxylic anhydride and 300mL acetic anhydride, stir evenly, and are slowly heated to 80 DEG C, and insulated and stirred is reacted 6 hours, and reaction is completed.
Most of solvent is recycled in vacuum distillation.Residue is poured into 1L ice water, with sodium bicarbonate tune pH to alkalescent,
A large amount of faint yellow solids are precipitated.Decompression filters, and collects filter cake, obtains 249g faint yellow solid, yield with re-crystallizing in ethyl acetate
91.2%.
The preparation of step 2:4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
It is stirred at room temperature down, intermediate obtained by 1L toluene and 249g previous step is sequentially added into 2L reaction flask, stirring is equal
It is even, then 62.5g hydrazine hydrochloride is added thereto, it stirs evenly, is heated to 60 DEG C and reacts 8 hours, reaction is completed.
Reaction solution filters while hot, and filtrate ice-water bath cooling crystallization obtains the powdered sterling of 244g faint yellow solid, HPLC
Purity 96.3%, yield 86.4%.
Nuclear magnetic data: 1H NMR (400MHz, DMSO-d6): δ 8.6 (bs, 4H), 7.65 (d, 2H), 7.13 (d, 2H),
6.97 (s, 2H), 2.58 (t, 2H), 2.19 (t, 2H), 1.92 (m, 2H).
Example 2 prepares the process of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
This example is to prepare the process of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride, including walk as follows
It is rapid:
Step 1: the preparation of intermediate
600mL toluene, 212g 4- (4- aminophenyl) methyl butyrate, 126g maleic are sequentially added into 3L reaction flask
Dicarboxylic anhydride and 360mL acetic anhydride, stir evenly, and are slowly heated to 80 DEG C, and insulated and stirred is reacted 7 hours, and reaction is completed.
Most of solvent is recycled in vacuum distillation.Residue is poured into 1.2L ice water, with sodium bicarbonate tune pH to weak base
Property, a large amount of faint yellow solids are precipitated.Decompression filters, and collects filter cake, obtains 289g faint yellow solid with re-crystallizing in ethyl acetate, receives
Rate 91.8%.
The preparation of step 2:4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
It is stirred at room temperature down, intermediate obtained by 1.2L toluene and 289g previous step is sequentially added into 3L reaction flask, stir
Uniformly, then thereto 68g hydrazine hydrochloride is added, stirs evenly, is heated to 60 DEG C and reacts 8 hours, reaction is completed.
Reaction solution filters while hot, and filtrate ice-water bath cooling crystallization obtains the powdered sterling of 282g faint yellow solid, HPLC
Purity 97.3%, yield 82.8%.
Nuclear magnetic data: 1H NMR (400MHz, DMSO-d6): δ 8.7 (bs, 4H), 7.55 (d, 2H), 7.23 (d, 2H),
6.95 (s, 2H), 2.68 (t, 2H), 2.29 (t, 2H), 1.95 (m, 2H).
Example 3 prepares the process of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
This example is to prepare the process of 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride, including walk as follows
It is rapid:
Step 1: the preparation of intermediate
It is suitable that 500mL methylene chloride, 193g 4- (4- aminophenyl) methyl butyrate, 105g are sequentially added into 2L reaction flask
Anhydride maleique and 300mL phthalic anhydride, stir evenly, and are slowly heated to 100 DEG C, and insulated and stirred is reacted 6 hours, and reaction is completed.
Most of solvent is recycled in vacuum distillation.Residue is poured into 1L ice water, with sodium bicarbonate tune pH to alkalescent,
A large amount of faint yellow solids are precipitated.Decompression filters, and collects filter cake, obtains 252g faint yellow solid, yield with re-crystallizing in ethyl acetate
92.3%.
The preparation of step 2:4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride
It is stirred at room temperature down, intermediate obtained by 1L dimethylbenzene and 252g previous step is sequentially added into 2L reaction flask, stir
Uniformly, then thereto 65g hydrazine hydrochloride is added, stirs evenly, is heated to 80 DEG C and reacts 8 hours, reaction is completed.
Reaction solution filters while hot, and filtrate ice-water bath cooling crystallization obtains the powdered sterling of 248g faint yellow solid, HPLC
Purity 98.3%, yield 88.2%.
Nuclear magnetic data: 1H NMR (400MHz, DMSO-d6): δ 8.7 (bs, 4H), 7.85 (d, 2H), 7.23 (d, 2H),
6.97 (s, 2H), 2.88 (t, 2H), 2.29 (t, 2H), 1.82 (m, 2H).
It should be understood that above-mentioned specific embodiment of the invention is used only for embodiment explanation or explains the present invention
Principle, but not to limit the present invention.Therefore, that is done without departing from spirit and scope of the present invention appoints
What modification, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.In addition, appended claims of the present invention
Whole variations for being intended to cover to fall into attached claim scope and boundary or this range and the equivalent form on boundary and
Modification.
Claims (9)
1. a kind of process for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride, wherein including walking as follows
It is rapid:
Step 1: using 4- (4- aminophenyl) methyl butyrate as raw material, in the catalytic action of anhydride compound and organic solvent
Under, intermediate is obtained with maleic acid anhydride reactant;
Step 2: the intermediate obtained in step 1 is obtained 4- (4- with hydrochloric acid hydrazine reaction under the action of organic solvent
N- maleimide phenyl) butyric acid hydrazides hydrochloride.
2. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the anhydride compound in step 1 is one of acetic anhydride, phthalic anhydride, succinic anhydride or a variety of.
3. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the organic solvent in step 1 is methylene chloride, chloroform, acetonitrile, toluene, dimethylbenzene, tetrahydrofuran, 2- methyl four
One of hydrogen furans, glycol dimethyl ether, ethylene glycol diethyl ether or diethylene glycol dimethyl ether are a variety of.
4. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the dosage of the maleic anhydride in step 1 is 0.5-5 equivalent.
5. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the dosage of the anhydride compound in step 1 is 1-10 equivalent.
6. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the range of reaction temperature of step 1 is -20~200 DEG C.
7. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the organic solvent in step 2 is methylene chloride, chloroform, acetonitrile, methanol, ethyl alcohol, acetone, ethyl acetate, acetic acid
Butyl ester, toluene, dimethylbenzene, tetrahydrofuran, 2- methyltetrahydrofuran, glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol two
One of methyl ether, 2- butanone or NMP or a variety of.
8. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the dosage of the hydrazine hydrochloride in step 2 are as follows: 0.5-10 equivalent.
9. the process according to claim 1 for preparing 4- (4-N- maleimide phenyl) butyric acid hydrazides hydrochloride,
Wherein, the range of reaction temperature of step 2 is -20~200 DEG C.
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4604396A (en) * | 1985-09-26 | 1986-08-05 | Merck & Co., Inc. | [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]ethanimidamides and [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]ethanimidic acid hydrazides, their derivatives and their salts |
US20020019343A1 (en) * | 1996-09-11 | 2002-02-14 | Felix Kratz | Antineoplastic conjugates of transferrin, albumin and polyethylene glycol |
US6582928B1 (en) * | 1992-08-05 | 2003-06-24 | Genentech, Inc. | Carbohydrate-directed cross-linking reagents |
CN1772730A (en) * | 2004-11-08 | 2006-05-17 | 株式会社上野制药应用研究所 | Hydroxynaphthoic acid hydrazide compounds and method for preparing the same |
CN101180280A (en) * | 2005-03-24 | 2008-05-14 | 弗·哈夫曼-拉罗切有限公司 | 1,2,4-triazole-5-one compounds as heterocyclic reverse transcriptase inhibitors |
CN102898345A (en) * | 2012-10-19 | 2013-01-30 | 上海化学试剂研究所 | Preparation method of N-(2, 4, 6-trichlorophenyl) maleimide |
CN110621673A (en) * | 2017-04-06 | 2019-12-27 | 杭州多禧生物科技有限公司 | Double-stranded linked cytotoxic drug conjugates |
-
2019
- 2019-05-22 CN CN201910426858.7A patent/CN110054580A/en active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4604396A (en) * | 1985-09-26 | 1986-08-05 | Merck & Co., Inc. | [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]ethanimidamides and [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]ethanimidic acid hydrazides, their derivatives and their salts |
US6582928B1 (en) * | 1992-08-05 | 2003-06-24 | Genentech, Inc. | Carbohydrate-directed cross-linking reagents |
US20020019343A1 (en) * | 1996-09-11 | 2002-02-14 | Felix Kratz | Antineoplastic conjugates of transferrin, albumin and polyethylene glycol |
CN1772730A (en) * | 2004-11-08 | 2006-05-17 | 株式会社上野制药应用研究所 | Hydroxynaphthoic acid hydrazide compounds and method for preparing the same |
CN101180280A (en) * | 2005-03-24 | 2008-05-14 | 弗·哈夫曼-拉罗切有限公司 | 1,2,4-triazole-5-one compounds as heterocyclic reverse transcriptase inhibitors |
CN102898345A (en) * | 2012-10-19 | 2013-01-30 | 上海化学试剂研究所 | Preparation method of N-(2, 4, 6-trichlorophenyl) maleimide |
CN110621673A (en) * | 2017-04-06 | 2019-12-27 | 杭州多禧生物科技有限公司 | Double-stranded linked cytotoxic drug conjugates |
Non-Patent Citations (4)
Title |
---|
A.H.BEDAIR等: "Synthesis and spectral studies on some 2-N-substituted phthalimides and phthaloyl p-aminophenyloxazolin-5-ones as possible antimicrobials", 《 JOURNAL OF THE SERBIAN CHEMICAL SOCIETY》 * |
PETR VLASAK等: "Synthesis of ring-substituted phenyl hydrazinecarboxylates and study of their protonation in dimethyl sulfoxide solutions", 《 COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS》 * |
崔岩等: "N - 苯基马来酰亚胺合成方法研究进展", 《山东化工》 * |
李志富等: "N-苯基马来酰亚胺合成工艺的改进", 《化学世界》 * |
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