CN115043757B - Method for continuously preparing benzamidine hydrochloride - Google Patents
Method for continuously preparing benzamidine hydrochloride Download PDFInfo
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- CN115043757B CN115043757B CN202210891543.1A CN202210891543A CN115043757B CN 115043757 B CN115043757 B CN 115043757B CN 202210891543 A CN202210891543 A CN 202210891543A CN 115043757 B CN115043757 B CN 115043757B
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- 238000000034 method Methods 0.000 title claims abstract description 15
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940125904 compound 1 Drugs 0.000 claims abstract description 9
- 229940125782 compound 2 Drugs 0.000 claims abstract description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims abstract description 3
- 238000005086 pumping Methods 0.000 claims abstract 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 238000007664 blowing Methods 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- XZHKVYYQQVEUBZ-UHFFFAOYSA-N [amino-(2-propoxyphenyl)methylidene]azanium;chloride Chemical compound Cl.CCCOC1=CC=CC=C1C(N)=N XZHKVYYQQVEUBZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000010924 continuous production Methods 0.000 claims 3
- NGMHLSBQVIXGNZ-UHFFFAOYSA-N (2-ethoxybenzenecarboximidoyl)azanium;chloride Chemical compound Cl.CCOC1=CC=CC=C1C(N)=N NGMHLSBQVIXGNZ-UHFFFAOYSA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- -1 methoxy, ethoxy Chemical group 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000012295 chemical reaction liquid Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003622 immobilized catalyst Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- ZDXKXSZWRWSJQU-UHFFFAOYSA-N n'-hydroxy-2-propoxybenzenecarboximidamide Chemical compound CCCOC1=CC=CC=C1C(N)=NO ZDXKXSZWRWSJQU-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical class CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- MXOQNVMDKHLYCZ-UHFFFAOYSA-N benzamidoxime Chemical compound ON=C(N)C1=CC=CC=C1 MXOQNVMDKHLYCZ-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical group C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
- B01J23/42—Platinum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/40—Catalysts, in general, characterised by their form or physical properties characterised by dimensions, e.g. grain size
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/50—Catalysts, in general, characterised by their form or physical properties characterised by their shape or configuration
- B01J35/51—Spheres
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/60—Catalysts, in general, characterised by their form or physical properties characterised by their surface properties or porosity
- B01J35/61—Surface area
- B01J35/615—100-500 m2/g
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to the technical field of synthesis of drug intermediates, in particular to a method for continuously preparing benzamidine hydrochloride; the method comprises the following steps:
Description
Technical Field
The invention relates to the technical field of synthesis of pharmaceutical intermediates, in particular to a method for continuously preparing benzamidine hydrochloride.
Background
Benzamidine hydrochloride is a key intermediate of vardenafil analogues, and is basically prepared by hydrogenation reduction of N-hydroxybenzamidine in an autoclave in the prior art, so that the safety risk is high, the catalyst is palladium carbon, and the catalyst is high in price.
Disclosure of Invention
The purpose of the invention is that: overcomes the technical defects of high price of the catalyst and high reaction safety coefficient in the prior art, and provides a method for continuously preparing benzamidine hydrochloride.
In order to achieve the above object, the present invention adopts the following technical scheme:
a process for the continuous preparation of benzamidine hydrochloride wherein the intermediate is 2-ethoxy (or 2-propoxybenzamidine hydrochloride comprising the steps of:
wherein: r is methoxy, ethoxy or propoxy;
the solution of the compound 1 and hydrogen are pumped into a fixed bed reactor filled with a catalyst respectively, and then react at a certain temperature and a certain pressure to generate the compound 2.
Further, the reaction temperature of the compound 1 solution in the fixed bed is 50-150 ℃, and the residence time of the reaction solution in the fixed bed is less than 15min.
Further, the solvent used in the solution of the compound 1 is one or more of methanol, ethanol, isopropanol and acetic acid.
Further, the catalyst is a supported platinum metal catalyst, and the supported catalyst carrier is SiO 2 、Al 2 O 3 Or one or more of activated carbon.
Further, the catalyst is a microsphere with the diameter of 0.5-4 mm.
Further, the catalyst is a microsphere with the diameter of 1-2 mm.
Further, the preparation method of the catalyst comprises the following steps:
s1, 15g of chloroplatinic acid and 800g of 5% NaOH aqueous solution are added, 50g of spherical active carbon (with the diameter of 1-2 mm) are soaked for 3-4h, and are filtered and dried by suction, and the mixture is dried to constant weight by blowing at the temperature of 100-110 ℃;
s2, after drying by blowing, transferring to a tube furnace, heating to 300-350 ℃ for 1h under the protection of nitrogen, switching to hydrogen, reducing for 2h at 300-350 ℃, switching to nitrogen, and slowly cooling to room temperature for standby;
s3, soaking for 24 hours by using 0.5% acetic acid aqueous solution, filtering, washing twice by using deionized water, and drying by blowing air for 24 hours at 100-110 ℃ to obtain 45-50.00g of Pt/C immobilized catalyst (spherical with the diameter of 1-2 mm).
Further, the mass concentration of the solution of the compound 1 is 5-15%, the reaction temperature is 50-150 ℃, the reaction pressure is 0.5-30 Mpa, and the reaction residence time is less than 15min.
Advantageous effects
The present market available platinum catalyst (mainly produced: shanxi Ruike, siam Kai) has irregular active carbon as carrier, and has the defects of uneven specific surface area, low mechanical strength, low activity and short service life.
The method is a continuous safe and reliable synthesis method, uses an inexpensive catalyst, and is an effective method suitable for industrial production. The reaction liquid does not need special treatment, and the purity of the product can reach more than 99 percent. Is an effective method which has simple and safe operation, low cost and easy industrialized production.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications. Unless otherwise stated, the temperature is usually at room temperature, and in the present invention, the room temperature is 10 to 30 ℃.
Example 1: preparation of the catalyst
(1) 15g of chloroplatinic acid, 800g of 5% NaOH aqueous solution and 50g of spherical active carbon (1-2 mm) are added, soaked for 4 hours, filtered and dried by suction, and the mixture is dried to constant weight by blowing at 100-110 ℃.
(3) After drying by blowing, transferring to a tube furnace, heating to 300-350 ℃ for 1h under the protection of nitrogen, switching hydrogen and reducing for 2h at 300-350 ℃, and switching nitrogen to slowly cool to room temperature for standby.
(4) Soaking in 0.5% acetic acid water solution for 24 hr, suction filtering, washing with deionized water twice, and air drying at 100-110 deg.c for 24 hr to obtain 48.00g Pt/C supported catalyst.
| Catalyst producer | Specific surface area (m 2/g) | Mechanical strength (N/grain) | Reaction conversion% | Life span |
| Siam Kaili | 100-200 | 20-30 | 90.0 | For 6 days |
| Homemade | 280-360 | 50-80 | 97.5 | For 10 days |
Example 2: intermittent mode
2-propoxy-N-hydroxybenzamidine (100.0 g), acetic acid (500 mL) and 10% palladium on carbon (10 g) are added into an autoclave, nitrogen is replaced for 3 times, hydrogen is replaced for 3 times, the temperature is raised to 60 ℃ for 4 to 8 hours, after the reaction is completed, the temperature is reduced to room temperature, palladium on carbon is filtered off, concentrated hydrochloric acid (80 g) is added, toluene (100 mL) is added, concentrated dry is carried out, 500mL methyl tertiary butyl ether is added for crystallization, 104.5g 2-propoxy benzamidine hydrochloride is obtained by suction filtration and drying, LC-MS (M+1): 179.20, HPLC purity is 99.2 percent, yield: 94.5%
Example 3: continuous mode
4.5g of self-made Pt/C immobilized catalyst is added into an European full-automatic hydrogenometer (5.6 mL of a filling column), after nitrogen replacement, the back pressure of hydrogen is switched to 2.5Mpa, hydrogen starts to be introduced, 35mL/min is started, a feed pump is started at the temperature of 80 ℃, raw material liquid containing 100g of 2-propoxy-N-hydroxybenzamidine, 500g of ethanol and 100g of acetic acid is conveyed into a reactor, the flow rate is 0.35mL/min, sampling is started after the system is stable, and the reaction is qualified. Concentrated hydrochloric acid (80 g) is added into the reaction solution, concentrated and dried, 500mL of methyl tertiary butyl ether is added for crystallization, and the mixture is filtered and dried by suction to obtain 106.0g of 2-propoxybenzamidine hydrochloride, LC-MS (M+1): 179.20,1HNMR (delta ppm, DMSO-d6, 400 MHz) 9.42 (s, 2H), 9.21 (s, 2H), 7.58-7.62 (t, 1H, J=4 Hz), 7.52-7.54 (d, 1H, J=8 Hz), 7.22-7.24 (d, 1H, J=8 Hz), 7.08-7.12 (t, 1H, J=4 Hz), 4.02-4.06 (t, 2H, J=8 Hz) 1.72-1.80 (M, 2H), 0.97-1.01 (t, 3H, J=4 Hz), HPLC purity 99.3%, yield: 95.9%.
Example 4: continuous mode
A55 mL packed column (with a jacket) was charged with 40.00g of a self-made Pt/C supported catalyst, the nitrogen back pressure was brought to 2.5MPa, hydrogen was switched in, hydrogen was introduced for 10min, and the flow rate was 250mL/min.
The jacket circulation oil temperature is set at 80 ℃, a feed pump is started after the temperature is constant, raw material liquid containing 500g of 2-propoxy-N-hydroxybenzylamide, 2500g of ethanol and 500g of acetic acid is conveyed into the reactor, the flow rate is 3.5mL/min, sampling is started after the system is stable, and the reaction is qualified. Concentrated hydrochloric acid (400 g) is added into the reaction solution, concentrated to dryness, 2.5L methyl tertiary butyl ether is added for crystallization, and 525.0g of 2-propoxybenzamidine hydrochloride is obtained after suction filtration and drying, the HPLC purity is 98.9%, and the yield is: 94.9%.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of the invention should be assessed as that of the appended claims.
Claims (4)
1. A process for the continuous preparation of benzamidine hydrochloride, either 2-ethoxybenzamidine hydrochloride or 2-propoxybenzamidine hydrochloride, characterized in that: the method comprises the following steps:
；
wherein: r is ethoxy or propoxy;
firstly, respectively pumping a solution of the compound 1 and hydrogen into a fixed bed reactor filled with a catalyst, and then, reacting at a certain temperature and a certain pressure to generate a compound 2;
the preparation method of the catalyst comprises the following steps:
s1, 15g of chloroplatinic acid and 800g of 5% NaOH aqueous solution are added, 50g of spherical active carbon with the diameter of 1-2mm is soaked for 3-4 hours, and is filtered and dried by suction, and the mixture is dried to constant weight by blowing at 100-110 ℃;
s2, after drying by blowing, transferring to a tube furnace, heating to 300-350 ℃ for 1h under the protection of nitrogen, switching to hydrogen, reducing for 2h at 300-350 ℃, switching to nitrogen, and slowly cooling to room temperature for standby;
s3, soaking for 24 hours by using 0.5% acetic acid aqueous solution, filtering, washing twice by using deionized water, and drying for 24 hours by blowing at 100-110 ℃ to obtain 45-50.00g of Pt/C supported catalyst, wherein the diameter of the supported catalyst is 1-2mm spherical.
2. A continuous process for the preparation of benzamidine hydrochloride as claimed in claim 1, wherein: the reaction temperature of the compound 1 solution in the fixed bed is 50-150 ℃, and the residence time of the reaction solution in the fixed bed is less than 15min.
3. A continuous process for the preparation of benzamidine hydrochloride as claimed in claim 1, wherein: the solvent used in the solution of the compound 1 is one or more of methanol, ethanol, isopropanol and acetic acid.
4. A continuous process for the preparation of benzamidine hydrochloride as claimed in claim 1, wherein: the mass concentration of the solution of the compound 1 is 5% -15%, the reaction temperature is 50-150 ℃, the reaction pressure is 0.5-30 mpa, and the reaction residence time is less than 15min.
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| CN115043757B true CN115043757B (en) | 2023-08-08 |
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Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481386A (en) * | 2000-12-18 | 2004-03-10 | Method for producing sulfonamide-substituted imidazotriazinones | |
| CN1489575A (en) * | 2001-01-29 | 2004-04-14 | ������������ʽ���� | Benzamidine derivatives and process for producing same |
| CN1830955A (en) * | 2005-11-07 | 2006-09-13 | 山东师范大学 | Method for synthesizing O-ethoxy phenyl formamidine acetate |
| CN1846852A (en) * | 2005-04-15 | 2006-10-18 | 北京有色金属研究总院 | Prepn process of carbon supported platinum catalyst |
| CN1894235A (en) * | 2003-12-19 | 2007-01-10 | 弗·哈夫曼-拉罗切有限公司 | N-(4-carbamimidoyl-benzyl) -2-alkoxy-2-heterocyclyl acetamides as inhibitors of the formation of coagulation factors xa, ixa and thrombin induced by factor viia |
| CN101029023A (en) * | 2007-02-02 | 2007-09-05 | 广东东阳光药业有限公司 | Production of picolyl ether and its salt |
| CN101502797A (en) * | 2008-12-30 | 2009-08-12 | 西安凯立化工有限公司 | Platinum-based selective hydrogenation catalyst as well as preparation method and use thereof |
| CN103349983A (en) * | 2013-07-27 | 2013-10-16 | 西安凯立化工有限公司 | Catalyst for preparing halogenated aniline through catalytic hydrogenation of halogenated nitrobenzene and application thereof |
| CN104549235A (en) * | 2014-12-19 | 2015-04-29 | 上海交通大学 | Preparation method of carbon supported nano platinum catalyst |
| CN106252677A (en) * | 2016-08-03 | 2016-12-21 | 陕西瑞科新材料股份有限公司 | A kind of preparation method of charcoal platinum catalyst |
| CN106565539A (en) * | 2016-11-05 | 2017-04-19 | 王密治 | Method for synthesizing benzamidine derivative |
| CN110878032A (en) * | 2019-10-31 | 2020-03-13 | 苏州诚和医药化学有限公司 | Synthesis method of N-benzylacetamidine hydrochloride |
| CN112934218A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | Platinum-carbon catalyst, preparation and application thereof |
-
2022
- 2022-07-27 CN CN202210891543.1A patent/CN115043757B/en active Active
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1481386A (en) * | 2000-12-18 | 2004-03-10 | Method for producing sulfonamide-substituted imidazotriazinones | |
| CN1489575A (en) * | 2001-01-29 | 2004-04-14 | ������������ʽ���� | Benzamidine derivatives and process for producing same |
| CN1894235A (en) * | 2003-12-19 | 2007-01-10 | 弗·哈夫曼-拉罗切有限公司 | N-(4-carbamimidoyl-benzyl) -2-alkoxy-2-heterocyclyl acetamides as inhibitors of the formation of coagulation factors xa, ixa and thrombin induced by factor viia |
| CN1846852A (en) * | 2005-04-15 | 2006-10-18 | 北京有色金属研究总院 | Prepn process of carbon supported platinum catalyst |
| CN1830955A (en) * | 2005-11-07 | 2006-09-13 | 山东师范大学 | Method for synthesizing O-ethoxy phenyl formamidine acetate |
| CN101029023A (en) * | 2007-02-02 | 2007-09-05 | 广东东阳光药业有限公司 | Production of picolyl ether and its salt |
| CN101502797A (en) * | 2008-12-30 | 2009-08-12 | 西安凯立化工有限公司 | Platinum-based selective hydrogenation catalyst as well as preparation method and use thereof |
| CN103349983A (en) * | 2013-07-27 | 2013-10-16 | 西安凯立化工有限公司 | Catalyst for preparing halogenated aniline through catalytic hydrogenation of halogenated nitrobenzene and application thereof |
| CN104549235A (en) * | 2014-12-19 | 2015-04-29 | 上海交通大学 | Preparation method of carbon supported nano platinum catalyst |
| CN106252677A (en) * | 2016-08-03 | 2016-12-21 | 陕西瑞科新材料股份有限公司 | A kind of preparation method of charcoal platinum catalyst |
| CN106565539A (en) * | 2016-11-05 | 2017-04-19 | 王密治 | Method for synthesizing benzamidine derivative |
| CN110878032A (en) * | 2019-10-31 | 2020-03-13 | 苏州诚和医药化学有限公司 | Synthesis method of N-benzylacetamidine hydrochloride |
| CN112934218A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | Platinum-carbon catalyst, preparation and application thereof |
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