CN102557964A - Synthesis method for N-Methyl-o-Phenylenediamine (salt) and isomeride thereof - Google Patents
Synthesis method for N-Methyl-o-Phenylenediamine (salt) and isomeride thereof Download PDFInfo
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- CN102557964A CN102557964A CN2010105804792A CN201010580479A CN102557964A CN 102557964 A CN102557964 A CN 102557964A CN 2010105804792 A CN2010105804792 A CN 2010105804792A CN 201010580479 A CN201010580479 A CN 201010580479A CN 102557964 A CN102557964 A CN 102557964A
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- methyl
- phenylenediamine
- salt
- isomers
- nitroaniline
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- RPKCLSMBVQLWIN-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1N RPKCLSMBVQLWIN-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 150000003839 salts Chemical class 0.000 title claims abstract description 14
- 238000001308 synthesis method Methods 0.000 title abstract 5
- ZXKXJHAOUFHNAS-FVGYRXGTSA-N (S)-fenfluramine hydrochloride Chemical compound [Cl-].CC[NH2+][C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 ZXKXJHAOUFHNAS-FVGYRXGTSA-N 0.000 title abstract 2
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 238000007069 methylation reaction Methods 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 230000001035 methylating effect Effects 0.000 claims description 10
- XIFJZJPMHNUGRA-UHFFFAOYSA-N n-methyl-4-nitroaniline Chemical compound CNC1=CC=C([N+]([O-])=O)C=C1 XIFJZJPMHNUGRA-UHFFFAOYSA-N 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001447 alkali salts Chemical class 0.000 claims description 3
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 3
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 abstract description 12
- 239000005537 C09CA07 - Telmisartan Substances 0.000 abstract description 6
- 229960005187 telmisartan Drugs 0.000 abstract description 6
- 239000006227 byproduct Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 238000010977 unit operation Methods 0.000 abstract description 2
- 230000011987 methylation Effects 0.000 abstract 3
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 3
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 2
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- DKEONVNYXODZRQ-UHFFFAOYSA-N hydron;2-n-methylbenzene-1,2-diamine;dichloride Chemical compound Cl.Cl.CNC1=CC=CC=C1N DKEONVNYXODZRQ-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- IWRJMQUPCKSBFP-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine;hydrochloride Chemical compound Cl.CNC1=CC=CC=C1N IWRJMQUPCKSBFP-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method for a telmisartan intermediate, N-Methyl-o-phenylenediamine (salt), and isomeride thereof. According to the synthesis method, o (m or p)-nitroaniline is subjected to methylation under the action of a methylation reagent and a catalyst so as to obtain N-Methyl-o (m or p)-nitroaniline; and then under the action of a reducing agent, the N-Methyl-o (m or p)-nitroaniline is used to prepare the N-Methyl-o (m or p)-phenylenediamine. According to the synthesis method, the o (m or p)-nitroaniline is adopted as an initial material and is cheap and easy to get, the selectivity of actions of the methylation reagent is strong, and by-product of N, N-dimethyl is avoided. The reaction in the two steps are all subjected to conventional unit operation, the reaction is simple and convenient, and the yield and quality are high, so that the synthesis method is applicable to mass industrial production.
Description
Technical field
The present invention relates to a kind of new preparation route of husky smooth type of treatment hypertension drug telmisartan midbody, specifically is the compound method of a kind of N-methyl-o-phenylenediamine and salt thereof.
Background technology
N-methyl-o-phenylenediamine and salt thereof are the key intermediates of synthetic telmisartan (Telmisartan).Existing manufacturing technique mainly contains:
1. being starting raw material with the O-Phenylene Diamine, is that methylating reagent reflux in methyl alcohol prepares title product with the methyl iodide,
There has been following defective in this technology:
1. being raw material with the O-Phenylene Diamine, is that first reagent carries out methylation reaction with the methyl iodide, very easily produces N in this technology, N '-dimethyl-O-Phenylene Diamine, and quality product is difficult to guarantee;
2. the raw material O-Phenylene Diamine is the high carcinogenic compound, and there is very big security risk in Workshop Production;
3. under go on foot in the pyroreaction, N-methyl-o-phenylenediamine hydrochloride one adds and promptly produces a large amount of hydrochloric acid gas, not only very easily dash material, and the sour gas of emitting is extremely strong to corrosion on Equipment;
2. be starting raw material with the o-Nitrochlorobenzene, under the heating and pressurizing condition, make N-methyl ortho-nitrophenyl, make target compound through Raney nickel catalytic reduction with the excessive methylamine reaction.
There has been following defective in this technology:
1. the o-Nitrochlorobenzene price is more expensive, has improved the production cost of this midbody with this explained hereafter;
2. must under HTHP, react, the production safety coefficient is lower.
Summary of the invention
The object of the invention provides a kind of production safety, quality product are high, production technique is easy, production cost the is low synthetic telmisartan intermediate N methyl-o-phenylenediamine (salt) and the industrial production process of isomers thereof.
For reaching the foregoing invention purpose, concrete scheme of the present invention is: the compound method of a kind of telmisartan intermediate N methyl-o-phenylenediamine (salt) and isomers thereof, and its reaction scheme is following:
Reactions step (1): adjacent (, to) N-methyl-p-nitroaniline carries out methylation reaction and obtains product N-methyl neighbour (, to) N-methyl-p-nitroaniline under methylating reagent and catalyst action.
Reactions step (2): product N-methyl that step (1) obtains adjacent (, to) N-methyl-p-nitroaniline obtains N-methyl adjacent (, to) phenylenediamine under the effect of reductive agent.
The used methylating reagent of step (1) is wherein a kind of of methyl iodide, monobromethane, methyl-sulfate, methylcarbonate, formic acid, formaldehyde.
The used solvent that methylation reaction adopted of step (1) is: water, N, dinethylformamide, DMSO 99.8MIN., THF, acetone one or more mixture wherein.
The used catalyzer of step (1) is: wherein a kind of of yellow soda ash, salt of wormwood, sodium hydroxide, Pottasium Hydroxide.
The described reductive agent of step (2) is palladium carbon, metallic nickel and mixture thereof, iron powder, sulfide, wherein a kind of of tin and basic salt, zinc and its esters.
The described said solvent of step (2) is: water, methyl alcohol, ethanol, THF one or more mixture wherein.
The present invention has following advantage:
With adjacent (, to) N-methyl-p-nitroaniline is starting raw material, and raw material is cheap and easy to get, and is strong with methylating reagent effect selectivity, no N, N-dimethyl-by product.
Two-step reaction is conventional unit operation, reacts easy, and yield is high, and quality is high, is suitable for the big production of industry.
Embodiment
Principle of the present invention is following:
The compound method of a kind of N-methyl-o-phenylenediamine (salt) and isomers thereof, reaction scheme is:
Step (1): adjacent (, to) N-methyl-p-nitroaniline carries out methylation reaction and obtains product N-methyl neighbour (, to) N-methyl-p-nitroaniline under methylating reagent and catalyst action;
Step (2): product N-methyl that step (1) obtains adjacent (, to) N-methyl-p-nitroaniline obtains N-methyl adjacent (, to) phenylenediamine under the effect of reductive agent.
Wherein the described methylating reagent of step (1) is wherein a kind of of methyl iodide, monobromethane, methyl-sulfate, methylcarbonate, formic acid or formaldehyde.
Wherein step (1) solvent that described methylation reaction adopted is: water, N, dinethylformamide, DMSO 99.8MIN., THF, acetone one or more mixture wherein.
Wherein the described catalyzer of step (1) is: a kind of in yellow soda ash, salt of wormwood, sodium hydroxide, the Pottasium Hydroxide.
Wherein the described reductive agent of step (2) is palladium carbon, metallic nickel and mixture thereof, iron powder, sulfide, wherein a kind of of tin and basic salt, zinc and its esters.
Wherein the described said solvent of step (2) is: water, methyl alcohol, ethanol, THF one or more mixture wherein.
Example I
1, N-methyl o-Nitraniline is synthetic
With o-Nitraniline 40.0g, 0.29mol mixes with acetone 200ml, adds KOH32g, 0.57mol again; Drip methylating reagent methyl-sulfate 46g, 0.37mol behind the no raw material point of TLC monitoring, adds ammoniacal liquor 20.0ml; Normal pressure reclaims acetone to doing, and adds entry 200.0ml again, stirred crystallization, filtering separation; Oven dry gets N-methyl o-Nitraniline 42.0g, yield 95.3%.Purity＞99%.
2, the N-methyl-o-phenylenediamine is synthetic
With N-methyl o-Nitraniline 20.0g, 0.13mol and 100ml methanol mixed add 10%Pd/C 0.05g again and are added in the hydrogenation still, under 0.2-0.5MPa, feed hydrogen about 3 hours at 30-35 ℃.Filter, be added dropwise to thionyl chloride 17.8g in the filtrating, 0.15mol, cooling is filtered, and gets N-methyl-o-phenylenediamine dihydrochloride 25g, yield 98.4%.
Example II
1, N-methyl o-Nitraniline is synthetic
With 40.0g, the o-Nitraniline of 0.29mol and N, N-dimethyl-methylamine acyl 200ml mixes, and adds NaOH22.8g again; 0.57mol, dripping methylating reagent methyl iodide 52.5g, 0.37mol is behind the no raw material point of TLC monitoring; Add entry 200.0ml again, stirred crystallization, filtering separation; Oven dry gets N-methyl o-Nitraniline 42.0g, yield 95.3%.Purity＞99%.
2, the N-methyl-o-phenylenediamine is synthetic
In the 500ml reaction flask, add 100ml ethanol, the 5ml Glacial acetic acid min. 99.5, reduced iron powder 21.8g, 0.39mol adds N-methyl o-Nitraniline 20.0g again in 50-55 ℃ of stir-activating 30 minutes, and 0.13mol was warming up to back flow reaction about 2 hours.Filtered while hot is added dropwise to thionyl chloride 17.8g in the filtrating, 0.15mol, and cooling is filtered, and gets N-methyl-o-phenylenediamine dihydrochloride 22.8g, yield 90.0%.
Claims (6)
1. the compound method of a N-methyl-o-phenylenediamine (salt) and isomers thereof, it is characterized in that: reaction scheme is:
Step (1): adjacent (, to) N-methyl-p-nitroaniline carries out methylation reaction and obtains product N-methyl neighbour (, to) N-methyl-p-nitroaniline under methylating reagent and catalyst action;
Step (2): product N-methyl that step (1) obtains adjacent (, to) N-methyl-p-nitroaniline obtains N-methyl adjacent (, to) phenylenediamine under the effect of reductive agent.
2. the compound method of N-methyl-o-phenylenediamine as claimed in claim 1 (salt) and isomers thereof is characterized in that: wherein the described methylating reagent of step (1) is wherein a kind of of methyl iodide, monobromethane, methyl-sulfate, methylcarbonate, formic acid or formaldehyde.
3. the compound method of N-methyl-o-phenylenediamine as claimed in claim 1 (salt) and isomers thereof; It is characterized in that; Wherein step (1) solvent that described methylation reaction adopted is: water, N, dinethylformamide, DMSO 99.8MIN., THF, acetone one or more mixture wherein.
4. the compound method of N-methyl-o-phenylenediamine as claimed in claim 1 (salt) and isomers thereof is characterized in that: wherein the described catalyzer of step (1) is: a kind of in yellow soda ash, salt of wormwood, sodium hydroxide, the Pottasium Hydroxide.
5. the compound method of N-methyl-o-phenylenediamine as claimed in claim 1 (salt) and isomers thereof; It is characterized in that: wherein the described reductive agent of step (2) is palladium carbon, metallic nickel and mixture thereof, iron powder, sulfide, wherein a kind of of tin and basic salt, zinc and its esters.
6. the compound method of N-methyl-o-phenylenediamine as claimed in claim 1 (salt) and isomers thereof is characterized in that: wherein the described said solvent of step (2) is: water, methyl alcohol, ethanol, THF one or more mixture wherein.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2010105804792A CN102557964A (en) | 2010-12-09 | 2010-12-09 | Synthesis method for N-Methyl-o-Phenylenediamine (salt) and isomeride thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105804792A CN102557964A (en) | 2010-12-09 | 2010-12-09 | Synthesis method for N-Methyl-o-Phenylenediamine (salt) and isomeride thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102942496A (en) * | 2012-11-28 | 2013-02-27 | 扬州工业职业技术学院 | Method for preparing (S)-N, N-dimethyl-3-(naphthol-1-oxygroup)-1- phenyl propyl group-1-amine |
| CN103626665A (en) * | 2013-11-08 | 2014-03-12 | 浙江工业大学 | Method for synthesizing N,N-dialkyl p-phenylenediamine |
| CN104892459A (en) * | 2015-06-16 | 2015-09-09 | 苏州明锐医药科技有限公司 | Riociguat intermediate and preparation method thereof |
| CN106631881A (en) * | 2016-09-08 | 2017-05-10 | 南京工业大学 | 2- (3-benzyl-2- (dimethylamino) phenyl) acetamide and its synthesis method and use |
| CN110272347A (en) * | 2019-07-18 | 2019-09-24 | 武汉本杰明医药股份有限公司 | A kind of synthetic method of N- methyl-o-phenylenediamine hydrochloride |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102942496A (en) * | 2012-11-28 | 2013-02-27 | 扬州工业职业技术学院 | Method for preparing (S)-N, N-dimethyl-3-(naphthol-1-oxygroup)-1- phenyl propyl group-1-amine |
| CN102942496B (en) * | 2012-11-28 | 2014-06-11 | 扬州工业职业技术学院 | Method for preparing (S)-N, N-dimethyl-3-(naphthol-1-oxygroup)-1- phenyl propyl group-1-amine |
| CN103626665A (en) * | 2013-11-08 | 2014-03-12 | 浙江工业大学 | Method for synthesizing N,N-dialkyl p-phenylenediamine |
| CN103626665B (en) * | 2013-11-08 | 2015-07-29 | 浙江工业大学 | The synthetic method of a kind of N, N-dialkyl-pphenylenediamines |
| CN104892459A (en) * | 2015-06-16 | 2015-09-09 | 苏州明锐医药科技有限公司 | Riociguat intermediate and preparation method thereof |
| CN106631881A (en) * | 2016-09-08 | 2017-05-10 | 南京工业大学 | 2- (3-benzyl-2- (dimethylamino) phenyl) acetamide and its synthesis method and use |
| CN110272347A (en) * | 2019-07-18 | 2019-09-24 | 武汉本杰明医药股份有限公司 | A kind of synthetic method of N- methyl-o-phenylenediamine hydrochloride |
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Application publication date: 20120711 |