CN111072570A - Preparation method of medicine for treating fasciolopsiasis - Google Patents
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Abstract
The invention provides a preparation method of Triclabendazole. Compared with the existing synthetic route which has more and complicated reaction steps, the preparation method of the invention has the advantages of less reaction steps, simple and convenient separation and improvement of the total yield and the operability of the reaction.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a preparation method of a medicine for treating fasciolopsiasis.
Background
Fasciolosis, also known as paragonimiasis, is a neglected tropical disease. There are approximately 240 million patients worldwide, with an additional 1.8 million people at risk.
13.2.2019, tricabendazole (also known as Triclabendazole) approved by nova by FDA is marketed in the form of dosage forms: 250mg tablet, trade name: egaten, for clinical use in treating patients with fascioliasis (fascioliasis) over 6 years of age. Egaten is currently the only recommended treatment by the World Health Organization (WHO) for fascioliasis, which is one of the drugs on the WHO's basic drug standard list.
A compound of formula I of Triclavazole:
the existing preparation method of Triclavendazole still needs to be improved.
Disclosure of Invention
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. Therefore, the invention aims to provide a drug Triclabendazole for treating fascioliasis and a preparation method thereof. Compared with the existing synthetic route, the preparation method has the advantages of more and complex reaction steps, fewer reaction steps, simple and convenient separation and improvement of the total yield and operability of the reaction.
In one aspect of the invention, the invention provides a process for preparing a compound of formula I. According to an embodiment of the invention, the method comprises:
(1) contacting a compound represented by formula 1 with a compound represented by formula 2 to obtain a compound represented by formula 3;
(2) reacting a compound represented by the formula 3 with CH3I, so as to obtain a compound shown as a formula 4;
(3) contacting a compound represented by formula 4 with a compound represented by formula 5 to obtain a compound represented by formula I, tricrabendazole,
the inventor finds that the target molecule, namely, tricrabendazole, is synthesized by performing ring closure on the obtained intermediate, namely 4, 5-diamino-2-chlorophenol (compound 1), serving as a starting material and carbon disulfide under the high-temperature condition through two halogenation reactions. The product obtained by carbon disulfide closed loop has poor solubility, can be directly separated out from a solvent, and provides convenience for product separation of the subsequent two-step reaction (column separation is not needed, and direct filtration or pulping purification is only needed). The method can be used for quickly and effectively preparing the compound shown in the formula I.
The term "contacting" as used herein is to be understood broadly and can be any means that enables a chemical reaction of at least two reactants, such as mixing the two reactants under appropriate conditions. The reactants to be contacted may be mixed with stirring as necessary, and thus, the type of stirring is not particularly limited, and may be, for example, mechanical stirring, that is, stirring under the action of a mechanical force.
Herein, a "compound of formula N" is also sometimes referred to herein as "compound N", where N is any integer from 1 to 5, e.g., "compound of formula 2" may also be referred to herein as "compound 2".
The terms "first", "second" and "first" are used herein for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
According to embodiments of the present invention, the above-described methods for preparing the compound of formula 3, the compound of formula 4, and the compound of formula I may further have at least one of the following additional features:
the chemical reactions described herein may be performed according to any method known in the art, according to embodiments of the present invention. The source of the raw materials for preparing the compound represented by formula 3, the compound represented by formula 4, and the compound represented by formula I is not particularly limited, and it may be prepared by any known method or may be commercially available.
According to an embodiment of the present invention, in step (1), the contacting manner of the compound represented by formula 1, the compound represented by formula 2, and the base is not particularly limited. Therefore, the efficiency of contacting the compound shown in the formula 1 and the compound shown in the formula 2 can be improved, the reaction speed is increased, and the efficiency of preparing the compound shown in the formula 3 by using the method is further improved.
According to an embodiment of the present invention, in the step (1), the following steps are included: and heating the compound 1, the compound 2 and the base in water at 0 ℃ until reflux reaction is carried out for 5 h. Cooling the reaction liquid to room temperature, filtering, and drying to obtain the compound shown in the formula 3.
According to an embodiment of the invention, in the step (1), the molar ratio of the compound 1, the compound 2 and the base is 1 (1.8-3) to (0.5-1.5), and preferably the molar ratio of the compound 1, the compound 2 and the base is 1:1.2: 0.7. Thus, the efficiency of preparing the compound represented by formula 3 using this method can be further improved.
According to an embodiment of the present invention, in step (1), the base is an organic base or an inorganic base, preferably the base is an inorganic base.
According to an embodiment of the present invention, in step (1), the inorganic base is at least one selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and potassium phosphate, and preferably the inorganic base is selected from the group consisting of sodium carbonate. Thus, the efficiency of preparing the compound represented by formula 3 using this method can be further improved.
According to the embodiment of the invention, in the step (1), the time of the reflux reaction is 4.5-5.5 hours.
According to a specific embodiment of the present invention, in the step (1), the following steps are included: compound 1(15.9g,0.1mol), Compound 2(15.9g,0.12mol), and Na were added to water (160mL) at 0 deg.C2CO3(15.9g,0.07mol), heated to reflux for 5 h. Cooling the reaction liquid to room temperature, filtering, and drying to obtain the compound shown in the formula 3.
According to an embodiment of the present invention, in step (2), the compound represented by formula 3, Et3N、CH3The contact manner of I is not particularly limited. Thus, the compound represented by the formula 3 and CH can be promoted3The efficiency of the contact I is improved, the reaction speed is accelerated, and the efficiency of preparing the compound shown in the formula 4 by using the method is further improved.
According to an embodiment of the present invention, in the step (2), the following steps are included: addition of Compound 3 and Et to THF3N, slowly adding CH dropwise under stirring3I, stirring and reacting. Cooling the reaction liquid to room temperature, filtering and drying to obtain the formula4.
According to an embodiment of the present invention, in the step (2), the compound represented by the formula 3, Et3N、CH3The molar ratio of I is 1 (1.0-1.5) to 1.0-1.2, preferably the compound represented by the formula 3 and Et3N、CH3The molar ratio of I is 1:1.2: 1.1. Thus, the efficiency of preparing the compound represented by formula 4 using this method can be further improved.
According to an embodiment of the present invention, in the step (2), the compound represented by the formula 3, Et, may be at 20 to 30 ℃3N、CH3I, stirring and reacting for 3.5-5 hours.
According to a specific embodiment of the present invention, in the step (2), the following steps are included: to THF (100mL) at 0 deg.C was added Compound 3(20.1g,0.1mol) and Et3N (12.1g,0.12mol), stirring and slowly adding CH dropwise3I (15.9g,0.11mol), stirred and reacted for 4h while maintaining 25 ℃. Cooling the reaction liquid to room temperature, filtering and drying to obtain the compound shown in the formula 4.
According to an embodiment of the present invention, in the step (3), the compound represented by formula 4, TEBA (benzyltriethylammonium chloride), K2CO3The contact manner of the compound represented by formula 5 is not particularly limited. Preferably, the solvent of the reaction is selected from THT (sulfolane). Thus, the compound represented by the formula 4, TEBA, K can be promoted2CO3And the contact efficiency of the compound shown in the formula 5 accelerates the reaction speed, and further improves the efficiency of preparing the compound shown in the formula I by using the method.
According to an embodiment of the present invention, in the step (3), the following steps are included: adding compound 4, TEBA, K to THT at room temperature2CO3Slowly adding the compound 5 under stirring, heating and stirring for reaction, cooling the reaction liquid to room temperature after the reaction is finished, and adding H2And O, stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound shown in the formula I. Therefore, the efficiency of preparing the compound Triclabendazole shown in the formula I by using the method can be further improved.
According to embodiments of the present inventionIn the step (3), a compound represented by the formula 4, TEBA, K2CO3The molar ratio of the compound represented by the formula 5 is 1 (0.08-0.015): (1.0-1.5): 1.0-1.3), preferably the compound represented by the formula 4, TEBA, K2CO3And the molar ratio of the compound shown in the formula 5 is 1: 0.1: 1.2:1.05. Therefore, the utilization rate of the reactants is high, the waste of raw materials and reality is avoided, and the yield of the target compound is high.
According to the embodiment of the invention, in the step (3), the compound represented by the formula 4, TEBA and K can be reacted at 90-100 DEG C2CO3And the compound shown in the formula 5 is stirred to react for 3.5-5 hours.
According to a specific embodiment of the present invention, in the step (3), the following steps are included: to THT (180mL) was added compound 4(21.5g,0.1mol), TEBA (2.28g,0.01mol), K at room temperature2CO3(16.56g,0.12mol), compound 5(19.05g,0.105mol) was slowly added with stirring, and after the addition, the reaction was stirred for 3 hours while the temperature was raised to 100 ℃. The reaction solution was cooled to room temperature, and H was added2O (180mL), stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound Triclabendazole shown in the formula I.
According to an embodiment of the present invention, the synthesis route of the compound Triclabendazole of formula I can be as follows:
compared with the prior art, the preparation method of Triclabendazole has the following beneficial effects: the preparation method adopts an available intermediate 4, 5-diamino-2-chlorophenol (compound 1) as an initial raw material, and the intermediate and carbon disulfide are subjected to ring closure under a high temperature condition, and a target molecule, namely Triclabendazole, is synthesized through two halogenation reactions. The product obtained by carbon disulfide closed loop has poor solubility, can be directly separated out from a solvent, and provides convenience for product separation of the subsequent two-step reaction (column separation is not needed, and direct filtration or pulping purification is only needed). Compared with the existing synthetic route, the synthetic method has the advantages of more and complex reaction steps, fewer reaction steps, simple and convenient separation and improvement of the total yield and operability of the reaction.
Detailed Description
The following describes embodiments of the present invention in detail. The following examples are illustrative only and are not to be construed as limiting the invention. The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
EXAMPLE 1 Synthesis of Compound represented by formula 3
Compound 1(15.9g,0.1mol), Compound 2(9.13g,0.12mol), and Na were added to purified water (160mL) at 0 deg.C2CO3(7.42g,0.07mol), heated to reflux for 5 h. The reaction solution was cooled to room temperature, filtered and dried to obtain 18.6g of the compound represented by formula 3 in 92.7% yield, which was used in the next reaction without purification of the compound represented by formula 3.
LC-MS(APCI):m/z＝201.2(M+1)+。
EXAMPLE 2 Synthesis of Compound represented by formula 3
Compound 1(15.9g,0.1mol), Compound 2(8.37g,0.11mol), and Na were added to purified water (160mL) at 0 deg.C2CO3(5.3g,0.05mol), heated to reflux for 4.5 h. The reaction solution was cooled to room temperature, filtered and dried to obtain 17.4g of the compound represented by formula 3, with a yield of 86.7%, which was used in the next reaction without purification.
EXAMPLE 3 Synthesis of Compound represented by formula 3
Compound 1(15.9g,0.1mol), Compound 2(10.66g,0.14mol), and Na were added to purified water (160mL) at 0 deg.C2CO3(15.9g,0.15mol), heated to reflux for 5.5 h. The reaction solution was cooled to room temperature, filtered and dried to obtain 17.6g of the compound represented by formula 3, with a yield of 87.7%, which was used in the next reaction without purification.
Example 4 Synthesis of Compound represented by formula 4
Compound (II) was added to THF (100mL) at 0 deg.CSubstance 3(20.1g,0.1mol) and Et3N (12.1g,0.12mol), stirring and slowly adding CH dropwise3I (15.9g,0.11mol), stirred and reacted for 4h while maintaining 25 ℃. The reaction solution was cooled to room temperature, filtered and dried to obtain 19.6g of a compound represented by formula 4 in a yield of 91.3%.
LC-MS(APCI):m/z＝215.2(M+1)+。
EXAMPLE 5 Synthesis of Compound represented by formula 4
To THF (100mL) at 0 deg.C was added Compound 3(15.9g,0.1mol) and Et3N (10.1g,0.1mol), stirring and slowly adding CH dropwise3I (14.2g,0.1mol), stirred and reacted for 3.5h while maintaining at 30 ℃. The reaction solution was cooled to room temperature, filtered and dried to obtain 19.5g of the compound represented by formula 4 with a yield of 90.8%.
EXAMPLE 6 Synthesis of Compound represented by formula 4
To THF (100mL) at 0 deg.C was added Compound 3(15.9g,0.1mol) and Et3N (15.2g,0.15mol), stirring and slowly adding CH dropwise3I (17.0g,0.12mol), stirred and reacted for 5h while maintaining 20 ℃. The reaction solution was cooled to room temperature, filtered and dried to obtain 19.0g of the compound represented by formula 4 in 88.5% yield.
EXAMPLE 7 Synthesis of Triclabendazole, a Compound of formula I
To THT (180mL) was added compound 4(21.5g,0.1mol), TEBA (2.28g,0.01mol), K at room temperature2CO3(16.56g,0.12mol), compound 5(19.05g,0.105mol) was slowly added with stirring, and after the addition, the reaction was stirred for 3 hours while the temperature was raised to 100 ℃. The reaction solution was cooled to room temperature, and H was added2O (180mL), stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound Triclabendazole shown in the formula I, wherein the yield is 27.8g, the yield is 77.3%, and the HPLC purity is 99.8%.
LC-MS(APCI):m/z＝359.2(M+1)+。
EXAMPLE 8 Synthesis of Triclabendazole, a Compound of formula I
To THT (180mL) was added compound 4(21.5g,0.1mol), TEBA (1.82g,0.008mol), K at room temperature2CO3(15.2g,0.11mol), slowly adding while stirringAfter the addition of compound 5(18.1g,0.1mol), the reaction mixture was heated to 90 ℃ and stirred for 5 hours. The reaction solution was cooled to room temperature, and H was added2O (180mL), stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound Triclabendazole shown in the formula I, wherein the yield is 26.5g, the yield is 73.7%, and the HPLC purity is 99.5%.
EXAMPLE 9 Synthesis of Triclabendazole, a Compound of formula I
To THT (180mL) was added compound 4(21.5g,0.1mol), TEBA (3.42g,0.015mol), K at room temperature2CO3(20.7g,0.15mol), compound 5(23.6g,0.13mol) was slowly added with stirring, and after the addition, the temperature was raised to 98 ℃ and the reaction was stirred for 4 hours. The reaction solution was cooled to room temperature, and H was added2O (180mL), stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound Triclabendazole shown in the formula I, wherein the yield is 25.7g, the yield is 71.5%, and the HPLC purity is 99.6%.
EXAMPLE 10 Synthesis of Triclabendazole, a Compound of formula I
To THT (180mL) was added compound 4(21.5g,0.1mol), TEBA (4.56g,0.02mol), K at room temperature2CO3(24.84g,0.18mol), compound 5(27.2g,0.15mol) was slowly added with stirring, and after the addition, the temperature was raised to 95 ℃ and the reaction was stirred for 3 hours. The reaction solution was cooled to room temperature, and H was added2O (180mL), stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound Triclabendazole shown in the formula I, wherein the yield is 24.2g, the yield is 67.3%, and the HPLC purity is 97.3%.
EXAMPLE 11 Synthesis of Triclabendazole, a Compound of formula I
To THT (180mL) was added compound 4(21.5g,0.1mol), TEBA (1.14g,0.005mol), K at room temperature2CO3(13.1g,0.095mol), compound 5(17.8g,0.098mol) was slowly added with stirring, and after the addition, the temperature was raised to 95 ℃ and the reaction was stirred for 3.5 hours. The reaction solution was cooled to room temperature, and H was added2O (180mL), stirring for 10min, vacuum filtering, drying, dissolving the obtained solid with acetone, decolorizing with activated carbon, adding purified water, and crystallizing to obtain the compound shown in formula IThe compound, Triclabendazole, was obtained in an amount of 14.0g, yield 38.9% and HPLC purity 98.0%.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.
Claims (10)
1. A method for preparing a compound tricrabendazole of formula I, comprising:
(1) contacting a compound represented by formula 1 with a compound represented by formula 2 to obtain a compound represented by formula 3;
(2) reacting a compound represented by the formula 3 with CH3I, so as to obtain a compound shown as a formula 4;
(3) contacting a compound represented by formula 4 with a compound represented by formula 5 to obtain a compound represented by formula I,
2. the method according to claim 1, wherein in step (1), the following steps are included: and heating the compound 1, the compound 2 and the base in water at 0 ℃ until reflux reaction is carried out for 5 h. Cooling the reaction liquid to room temperature, filtering, and drying to obtain the compound shown in the formula 3.
3. The method according to claim 2, wherein in the step (1), the molar ratio of the compound 1 to the compound 2 to the base is 1 (1.8-3) to (0.5-1.5), and preferably the molar ratio of the compound 1 to the compound 2 to the base is 1:1.2: 0.7.
Optionally, in step (1), the base is an organic base or an inorganic base, preferably the base is an inorganic base;
optionally, the inorganic base is at least one selected from sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium phosphate;
optionally, the inorganic base is selected from sodium carbonate.
Optionally, in the step (1), the reflux reaction time is 4.5-5.5 hours.
4. The method of claim 1, wherein in step (2), the following steps are included: addition of Compound 3 and Et to THF3N, slowly adding CH dropwise under stirring3I, stirring and reacting. Cooling the reaction liquid to room temperature, filtering and drying to obtain the compound shown in the formula 4.
5. A process according to claim 4, wherein in step (2), the compound represented by formula 3, Et3N、CH3The molar ratio of I is 1 (1.0-1.5) to 1.0-1.2, preferably the compound represented by the formula 3 and Et3N、CH3The molar ratio of I is 1:1.2: 1.1.
6. The method according to claim 4, wherein in the step (2), the compound represented by the formula 3 and Et are allowed to stand at 20 to 30 ℃3N、CH3I, stirring and reacting for 3.5-5 hours.
7. The method of claim 1, wherein in step (3), the following steps are included: adding compound 4, TEBA, K to THT at room temperature2CO3Slowly adding the compound 5 under stirring, heating and stirring for reaction, cooling the reaction liquid to room temperature after the reaction is finished, and adding H2And O, stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound shown in the formula I.
8. The method according to claim 7, wherein in the step (3), the compound represented by the formula 4, TEBA, K2CO3The molar ratio of the compound represented by the formula 5 is 1 (0.08-0.015): (1.0-1.5): 1.0-1.3), preferably the compound represented by the formula 4, TEBA, K2CO3And the molar ratio of the compound shown in the formula 5 is 1: 0.1: 1.2:1.05.
9. The method according to claim 7, wherein the compound of formula 4, TEBA, K, in step (2) can be reacted at 90-100 ℃2CO3And the compound shown in the formula 5 is stirred to react for 3.5-5 hours.
10. The method according to claims 1-9, wherein in step (1), the following steps are included: compound 1(15.9g,0.1mol), Compound 2(15.9g,0.12mol), and Na were added to water (160mL) at 0 deg.C2CO3(15.9g,0.07mol), heating to reflux reaction for 5h, cooling the reaction liquid to room temperature, filtering, and drying to obtain a compound shown in a formula 3;
the step (2) comprises the following steps: to THF (100mL) at 0 deg.C was added Compound 3(20.1g,0.1mol) and Et3N (12.1g,0.12mol), stirring and slowly adding CH dropwise3I (15.9g,0.11mol), keeping at 25 ℃, stirring and reacting for 4 hours, cooling the reaction liquid to room temperature, filtering, and drying to obtain a compound shown in a formula 4;
in the step (3), the method comprises the following steps: to THT (180mL) was added the combination at room temperatureSubstance 4(21.5g,0.1mol), TEBA (2.28g,0.01mol), K2CO3(16.56g,0.12mol), slowly adding compound 5(19.05g,0.105mol) under stirring, heating to 100 deg.C, stirring for reaction for 3H, cooling the reaction solution to room temperature, adding H2O (180mL), stirring for 10min, then carrying out suction filtration and drying, dissolving the obtained solid with acetone, decoloring with activated carbon, and adding purified water for crystallization to obtain the compound Triclabendazole shown in the formula I.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450939A (en) * | 2007-12-05 | 2009-06-10 | 沈阳药科大学 | Novel benzimidazoles compounds |
| CN106632067A (en) * | 2016-12-22 | 2017-05-10 | 杭州洪桥生物技术有限公司 | Method for preparing triclabendazole serving as medicine for animal distomiasis |
-
2019
- 2019-12-26 CN CN201911372946.XA patent/CN111072570A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450939A (en) * | 2007-12-05 | 2009-06-10 | 沈阳药科大学 | Novel benzimidazoles compounds |
| CN106632067A (en) * | 2016-12-22 | 2017-05-10 | 杭州洪桥生物技术有限公司 | Method for preparing triclabendazole serving as medicine for animal distomiasis |
Non-Patent Citations (2)
| Title |
|---|
| BRIAN IDDON等: "2H-Benzimidazoles (Isobenzimidazoles).Part 7.1 A New Route to Triclabendazole [5-Chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1H-benzimidazole] and Congeneric Benzimidazoles", 《J. CHEM. SOC》 * |
| 吴范宏 等: "抗肝吸虫药三氯苯达唑的合成", 《中国医药工业杂志》 * |
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Application publication date: 20200428 |