CN106831445A - A kind of preparation method of indenyl amines - Google Patents

A kind of preparation method of indenyl amines Download PDF

Info

Publication number
CN106831445A
CN106831445A CN201611029193.9A CN201611029193A CN106831445A CN 106831445 A CN106831445 A CN 106831445A CN 201611029193 A CN201611029193 A CN 201611029193A CN 106831445 A CN106831445 A CN 106831445A
Authority
CN
China
Prior art keywords
compound
under
generate
action
generated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201611029193.9A
Other languages
Chinese (zh)
Other versions
CN106831445B (en
Inventor
姚庆佳
武思民
徐杨军
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sphinx Drug Development (tianjin) Ltd By Share Ltd
Original Assignee
Sphinx Drug Development (tianjin) Ltd By Share Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sphinx Drug Development (tianjin) Ltd By Share Ltd filed Critical Sphinx Drug Development (tianjin) Ltd By Share Ltd
Priority to CN201611029193.9A priority Critical patent/CN106831445B/en
Publication of CN106831445A publication Critical patent/CN106831445A/en
Application granted granted Critical
Publication of CN106831445B publication Critical patent/CN106831445B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/62Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00Preparation of halogenated hydrocarbons
    • C07C17/093Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/10Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
    • C07C17/12Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00Preparation of carboxylic acid amides
    • C07C231/02Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00Preparation of carboxylic acid amides
    • C07C231/12Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C239/00Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
    • C07C239/08Hydroxylamino compounds or their ethers or esters
    • C07C239/14Hydroxylamino compounds or their ethers or esters having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/46Friedel-Crafts reactions
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/353Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/36Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/363Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to a kind of preparation method of indenyl amines, with 1,2 diethylbenzenes are initiation material to the compound, and compound 2 is generated by the catalytic bromination of Fe and I2;Under by being acted in butyl lithium compound 3 is generated with DMF;With malonic acid reacting generating compound 4 under piperidines effect;Compound 5 is reduced under Raney's nickel effect;Compound 6 is generated by the catalytic bromination of Fe and I2;Friedel-crafts acylation generation compound 7 is carried out under AlCl3 effects;With nitrous acid straight butyl reacting generating compound 8;Compound 9 is generated under Pd/C catalysis;With trifluoroacetic acid reacting generating compound 10;Alcoholic compound 11 is reduced into sodium borohydride reaction;Hydroxyl generation compound 12 is taken off under dimethylsilane and boron trifluoride effect;Trifluoroacetyl group generation target compound 13 is taken off under potassium carbonate effect.

Description

Preparation method of indenyl amine compound
Technical Field
The invention relates to the field of compound production, in particular to a preparation method of an indenyl amine compound.
Background
5,6-diethyl-2, 3-dihydro-1H-indene-2-amine hydrochloride in the indenylamine compound is an indacaterol intermediate, the English name is 5,6-diethyl-2, 3-dihydro-1H-inden-2-aminohydrochlorid, CAS 312753-53-0, the molecular formula is C13H19N.HCl, the molecular weight is 225.76, the density is 0.00285mmHg at 25 ℃, the purity is more than 99 percent of white solid, the melting point is more than 250 ℃, the intermediate is a new drug of COPD indacaterol for chronic obstructive pulmonary disease.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a preparation method of indenyl amine compound.
In order to solve the technical problems, the technical scheme of the invention is as follows:
an indenylamine compound, 4, 5-diethyl-2, 3-dihydro-1H-indene-2-amine hydrochloride, which has a structural formula shown in (I),
preferably, the NMR data of the indenyl amine compound, 4, 5-diethyl-2, 3-dihydro-1H-indene-2-amine hydrochloride, are 1.158 to 1.059(m, 6H), 2.617 to 2.503(m,4H),2.980 to 2.926(dd,2H),3.266 to 3.193(m,2H),3.972 to 3.960(b,1H),7.021(s,2H),8.382(b, 3H).
The preparation method of the indenyl amine compound takes 1, 2-diethylbenzene as a starting material, and obtains a target compound through 12 steps of reactions, and comprises the following specific steps:
(1) compound 1 is catalyzed by bromination of Fe and I2 to produce compound 2;
(2) compound 2 is reacted with DMF under the action of butyl lithium to generate compound 3;
(3) reacting the compound 3 with malonic acid under the action of piperidine to generate a compound 4;
(4) reducing the compound 4 into a compound 5 under the action of Raney nickel;
(5) compound 5 is catalytically brominated by Fe and I2 to produce compound 6;
(6) carrying out Friedel-crafts acylation reaction on the compound 6 under the action of AlCl3 to generate a compound 7;
(7) reacting the compound 7 with n-butyl nitrite to generate a compound 8;
(8) the compound 8 is catalyzed by Pd/C to generate a compound 9;
(9) reacting the compound 9 with trifluoroacetic acid to generate a compound 10;
(10) the compound 10 reacts with sodium borohydride and is reduced into an alcohol compound 11;
(11) removing hydroxyl from the compound 11 under the action of dimethylsilane and boron trifluoride to generate a compound 12;
(12) removing trifluoroacetyl from the compound 12 under the action of potassium carbonate to generate a target compound 13; wherein,
the specific reaction equation of the above-mentioned preparation method of the indenyl amine compound is as follows:
the invention has the beneficial effects that:
the indenyl amine compound 4, 5-diethyl-2, 3-dihydro-1H-indene-2-amine hydrochloride has application value in the aspect of preventing and treating respiratory diseases; the preparation method has the advantages of cheap and easily-obtained raw materials and simple synthesis method, is a brand new method for synthesizing the indenyl amine compound, and is suitable for the requirement of large-scale industrial production.
Drawings
FIG. 1 is a HNMR spectrum of 4, 5-diethyl-2, 3-dihydro-1H-inden-2-amine hydrochloride. The hydrogen spectrum data are as follows: 1.158-1.059(m, 6H), 2.617-2.503(m,4H),2.980-2.926(dd,2H),3.266-3.193(m,2H),3.972-3.960(b,1H),7.021(s,2H),8.382(b, 3H).
Detailed Description
In order to make those skilled in the art better understand the technical solution of the present invention, the following detailed description will be given with reference to specific embodiments.
Example 1
The preparation method of the 4, 5-diethyl-2, 3-dihydro-1H-indene-2-amine hydrochloride comprises the following specific steps:
(1) compound 1 was charged into a 5L three-necked flask, and 2.3g Fe and 0.1g I were added2126.3g Br were slowly added dropwise with stirring at 0 deg.C2The mixture was stirred at room temperature overnight. Detecting the reaction solution, confirming reaction completion by crude nuclear magnetic resonance (HNMR), adding appropriate amount of water into the system, extracting with ethyl acetate for 2 times, washing the organic phase with saturated sodium bisulfite aqueous solution and saturated sodium chloride aqueous solution twice, respectively, and adding anhydrous Na2SO4Drying and concentration gave 173g of a yellowish brown oily liquid (Compound 2). The yield thereof was found to be 90%.
(2) 360ml of n-BuLi was slowly added dropwise to a solution of 2173g of Compound 2 in 1L of THF at-80 ℃ and, after completion of the addition, stirred for 30min, DMF was added dropwise at-80 ℃ and, after completion of the addition, gradually returned to room temperature. Dot-panel detection (PE: EA: 30:1, R)fA value equal to about 0.5). Adding a proper amount of saturated aqueous ammonium chloride solution into the reaction solution, adding methyl tert-butyl ether, separating, extracting the aqueous phase for several times by using methyl tert-butyl ether until the aqueous phase has no ultraviolet point, combining the organic phases, washing the organic phases for three times by using saturated salt, drying and spin-drying to obtain 150g of yellow solid (compound 3) in total. Yield 114% (crude).
(3) 165.4g malonic acid, 450ml piperidineAdding 150g of compound 3 in pyridine solution in turn, heating and refluxing overnight, and detecting by spotting (PE: EA is 3:1, one drop of glacial acetic acid, RfValue about 0.5) after the reaction is finished, directly distilling and concentrating the reaction liquid under reduced pressure. And adding a 2M hydrochloric acid solution into the concentrated solution to separate out a large amount of yellow solid, adjusting the pH value to be less than 1, adding enough DCM to dissolve and separate the solid, extracting the water phase by DCM for several times until the water phase does not contain the target product, combining the organic phases, drying, spinning, mixing the sample, separating by a column (when the PE: DCM is 10:1, impurities come out, when the PE: DCM is 5:1, the raw material comes out, when the PE: DCM is 3:1, the product comes out, washing the product by pure DCM with 10mL of anhydrous formic acid added into each liter) to obtain 138.8g of yellow solid (compound 4) in total, wherein the yield is 70%.
(4) 26.5g of Raney nickel are taken out under argon protection, washed three times with 2.5L of methanol, 138.8g of compound 4 are added, hydrogen is introduced and stirring is carried out overnight at room temperature. The next day the crude product was taken for nmr detection, after reaction was complete, filtered and the filtrate was spin dried to give 135g of solid (compound 5) in 100% yield.
(5) 2.2g Fe, 0.1g I2 were added to 135g of Compound 5 in Dichloromethane (DCM) and 125.6g Br were added under ice water2Stirred at room temperature overnight. The next day plate detection (PE: EA ═ 5:1 with a drop of glacial acetic acid, RfValue equal to about 0.4), the reaction is complete, ice is added and a saturated aqueous solution of sodium bisulfite is added, the phases are separated, the aqueous phase is extracted twice with DCM, the organic phases are combined, dried, spun dry, sample-mixed, column-separated (PE: EA 50:1 → 30:1 → 10:1 → 5:1), and finally 140g of oily liquid (compound 6) was obtained in a total yield of 75%.
(6) 280ml of thionyl chloride were added to 140g of compound 6, heated to reflux and the reaction detected on a dot plate after one hour (PE: EA: 3:1, R)fValue about 0.4), the reaction solution was concentrated, 1.2L of DCM was added under ice bath, 72g of aluminum trichloride was added at 0 ℃ or lower, and the reaction was allowed to gradually rise to room temperature with stirring. Detection reaction (PE: EA: 20:1, R)fApproximately equal to 0.6), and after the reaction is completed, the reaction solution is started to be treated. Reacting the reaction solutionPouring into a hydrochloric acid solution with ice, extracting twice with DCM, combining the organic phases, drying, spin-drying, stirring with silica gel, and separating with a column (the product can be washed off directly with petroleum ether, and then the product can be washed off completely with increasing polarity step by step) to obtain 106g of a yellow solid (compound 7) with a yield of 80%.
(7) 21g n-BuONO, 19ml of concentrated hydrochloric acid, were added to a solution of 50g of Compound 7 in 800ml of MeOH under argon. Heating and stirring at the external temperature of 5 ℃. After four hours, spot plate detection (PE: EA 20:1, raw material R)fApproximately equal to 0.6), the starting materials were substantially reacted and filtered to obtain a total of 26g of a white solid (Compound 8). The yield thereof was found to be 47%.
(8) 10g of palladium on carbon and 26g of Compound 8 were put in a reaction flask containing 1L of methanol, 100ml of concentrated hydrochloric acid was added, and after replacing the air with a hydrogen balloon three times, the mixture was stirred at room temperature overnight. And (3) sending the crude product to nuclear magnetic detection, and directly spin-drying the reaction solution after the reaction is finished to obtain 26g of white solid (compound 9). The yield thereof was found to be 100%.
(9) 36.8g of TEA, 36.7g of trifluoroacetic acid (TFAA) were added slowly, in succession, dropwise to 21g of Compound 9 in a solvent of 1LTHF under argon Ar, the temperature being controlled at-10 ℃ and the mixture was stirred overnight at room temperature. The next day of plate detection (PE: EA: 5:1, rf value about 0.6), after completion of the reaction, 200mL of water and 200mL of EA were added to the reaction mixture, and the mixture was separated. The aqueous phase is then extracted three times with EA, the organic phases are combined, dried, stirred and separated by column separation (PE/THF system 10:1 product off) to give 26g of a pale yellow solid (compound 10). The yield thereof was found to be 99%.
(10) 4.3g of sodium borohydride were added to a solution of 25g of Compound 10 in 500ml of ethanol and stirred at room temperature. After one hour, dot plate detection (color development with phosphomolybdic acid, PE: EA: 5:1, R)fValue about 0.3), the starting material has not reacted completely, 1.1g of sodium borohydride are added and stirring is continued at room temperature. After half an hour, the reaction was completed by spotting and detection. To the reaction solution, 200mL of water and 3000mL of lea were added, followed by liquid separation, extraction of the aqueous phase twice with 100mL of EA, and the organic phases were combined, dried, spun-dried, and column-separated (PE: EA ═ 20:1 for impurities and 10:1 for product) to obtain 10g of a white solid (compound 11). The yield thereof was found to be 39.5%.
(11) 8ml of triethylsilane and 6.5ml of boron trifluoride diethyl etherate were added to a solution of 8.2g of Compound 11 in 1, 2-dichloroethane, respectively, and the mixture was refluxed at 80 ℃ and stirred with heating. After one hour, dot plate detection (phosphomolybdic acid color development, PE: EA: 5:1, R)fValue about 0.9), the starting material was reacted, and 100mL of water and 100mL of methylene chloride were added to the reaction mixture. The phases were separated and the aqueous phase was extracted twice with 50mL dichloromethane, the organic phases combined, dried, spun and column separated (petroleum ether washes away impurities and 80:1 washes out product) to give 4.5g white solid (Compound 12) in 58% yield.
(12) 4.5g of Compound 12 and 4.2g of potassium carbonate were added to a mixed solution of 100ml of methanol and 50ml of water, respectively, heated to 85 ℃ and stirred. After half an hour, dot panel detection (PE: EA: 10:1, R)fThe value is equal to about 0.7), and the hydrolysis reaction of the raw materials is finished. To the reaction solution were added 50mL of Ethyl Acetate (EA) and 50mL of water, followed by liquid separation, drying of the organic phase, and concentration to obtain a product. And continuously adding a small amount of methyl tert-butyl ether to dissolve, adding 2mL of concentrated hydrochloric acid to separate out a large amount of solid, adding 50mL of n-hexane, and washing the solid. The solid was filtered off and dried under reduced pressure to give the desired product compound 13 in a total of 3.1g, yield 86.9%. As shown in FIG. 1, HNMR spectrum (CDCl) of 4, 5-diethyl-2, 3-dihydro-1H-indene-2-amine hydrochloride3) The hydrogen spectrum data is as follows: 1.158-1.059(m, 6H), 2.617-2.503(m,4H),2.980-2.926(dd,2H),3.266-3.193(m,2H),3.972-3.960(b,1H),7.021(s,2H),8.382(b, 3H).
The specific reaction equation is as follows:
application test example
Male SD rats, aged 4-6 weeks for months, weighing 130-.
First group-asthmatic group, each largeMouse intraperitoneal injection of antigen solution 1ml (containing egg protein 100mg, inactivated Bordetella pertussis vaccine 5 x 10)9And 100mg of aluminum hydroxide dry powder) sensitization;
the second group, asthma treatment group, was a group in which each rat was gavaged with 1.2. mu.g/kg of the compound obtained in example 1, 1 time every 12 hours, and three days later, each rat was intraperitoneally injected with 1ml of antigen solution (containing 100mg of egg protein, inactivated Bordetella pertussis vaccine 5. about.10)9And 100mg of aluminum hydroxide dry powder).
The results showed that the first group, asthma-group antigen challenge, immediately exhibited shortness of breath, flaccidity of limbs, sluggish movement or pronation, while the second group, asthma-treated group showed no significant response. The compound of the invention has certain inhibition effect on asthma.
The above detailed description of the process for the preparation of an indenyl amine compound with reference to specific embodiments is illustrative and not restrictive, and several examples are set forth within the limits of the invention, and therefore variations and modifications may be made without departing from the general inventive concept within the scope of the present invention.

Claims (1)

1. A process for the preparation of an indenylamine compound which is 4, 5-diethyl-2, 3-dihydro-1H-inden-2-amine hydrochloride, characterized in that: 1, 2-diethylbenzene is used as a starting material, and a target compound is obtained through 12 steps of reaction, and the method comprises the following specific steps:
(1) compound 1 is catalyzed by bromination of Fe and I2 to produce compound 2;
(2) compound 2 is reacted with DMF under the action of butyl lithium to generate compound 3;
(3) reacting the compound 3 with malonic acid under the action of piperidine to generate a compound 4;
(4) reducing the compound 4 into a compound 5 under the action of Raney nickel;
(5) compound 5 is catalytically brominated by Fe and I2 to produce compound 6;
(6) carrying out Friedel-crafts acylation reaction on the compound 6 under the action of AlCl3 to generate a compound 7;
(7) reacting the compound 7 with n-butyl nitrite to generate a compound 8;
(8) the compound 8 is catalyzed by Pd/C to generate a compound 9;
(9) reacting the compound 9 with trifluoroacetic acid to generate a compound 10;
(10) the compound 10 reacts with sodium borohydride and is reduced into an alcohol compound 11;
(11) removing hydroxyl from the compound 11 under the action of dimethylsilane and boron trifluoride to generate a compound 12;
(12) removing trifluoroacetyl from the compound 12 under the action of potassium carbonate to generate a target compound 13; wherein,
CN201611029193.9A 2016-11-22 2016-11-22 A kind of preparation method of indenyl amine compounds Active CN106831445B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201611029193.9A CN106831445B (en) 2016-11-22 2016-11-22 A kind of preparation method of indenyl amine compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201611029193.9A CN106831445B (en) 2016-11-22 2016-11-22 A kind of preparation method of indenyl amine compounds

Publications (2)

Publication Number Publication Date
CN106831445A true CN106831445A (en) 2017-06-13
CN106831445B CN106831445B (en) 2019-01-22

Family

ID=59145882

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201611029193.9A Active CN106831445B (en) 2016-11-22 2016-11-22 A kind of preparation method of indenyl amine compounds

Country Status (1)

Country Link
CN (1) CN106831445B (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5708018A (en) * 1993-08-06 1998-01-13 Pharmacia & Upjohn Company 2-aminoindans as selective dopamine D3 ligands
WO2000026173A1 (en) * 1998-11-03 2000-05-11 Ligand Pharmaceuticals Incorporated Novel retinoids, methods for their production and use
CN1212119C (en) * 2000-12-04 2005-07-27 诺瓦提斯公司 Organic compounds
CN103360264A (en) * 2013-07-18 2013-10-23 武汉恒和达生物医药有限公司 Synthesizing method of indacaterol amino fragment 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride
CN103539677A (en) * 2012-07-16 2014-01-29 武汉万知生物医药有限公司 Preparation method of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5708018A (en) * 1993-08-06 1998-01-13 Pharmacia & Upjohn Company 2-aminoindans as selective dopamine D3 ligands
WO2000026173A1 (en) * 1998-11-03 2000-05-11 Ligand Pharmaceuticals Incorporated Novel retinoids, methods for their production and use
CN1212119C (en) * 2000-12-04 2005-07-27 诺瓦提斯公司 Organic compounds
CN103539677A (en) * 2012-07-16 2014-01-29 武汉万知生物医药有限公司 Preparation method of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride
CN103360264A (en) * 2013-07-18 2013-10-23 武汉恒和达生物医药有限公司 Synthesizing method of indacaterol amino fragment 5,6-diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SYLVAIN RAULT: "Une Synthese simple des premieres amino-3 indanones-1", 《BULLETIN DE LA SOCIETE CHIMIQUE DE FRANCE》 *

Also Published As

Publication number Publication date
CN106831445B (en) 2019-01-22

Similar Documents

Publication Publication Date Title
CN107827816B (en) Method for synthesizing formamide derivative through graphene oxide catalytic formylation reaction
CN114315776B (en) Method for preparing 2, 4-disubstituted tetrahydropyran compound through hydrogenolysis reaction
CN114213360A (en) Preparation method of trimetazidine
CN106831445B (en) A kind of preparation method of indenyl amine compounds
CN102911160A (en) Method for preparing and purifying dabigatran etexilate intermediate
Engelbrech et al. Stereoselective palladium catalyzed cyclization on carbohydrate templates-a route to chiral cyclopentanes and some heterocyclic analogs
CN109251138A (en) A kind of preparation method of all natural carbon source raspberry ketone
CN115160148A (en) High-selectivity method for synthesizing N-allylbenzylamine
CN108484451A (en) A kind of method that one kettle way prepares 1,2- alkamine compounds
CN104610218A (en) Xanthene-1,8-diketone derivatives as well as preparation method and application thereof
CN101481333A (en) Novel rivastigmine preparation
CN111269128B (en) Synthesis method of 1,1' - (hexa-2, 4-diyne-1, 6-diyl) bis (3-alkyl urea) compound
CN110294768B (en) Method for synthesizing pinoxaden through 2, 6-diethyl-4-methyl phenylmalonate
CN109232222B (en) Preparation method of (E) -octyl-4-ene-1, 8-diacid
CN107879967B (en) Preparation method of 1-azaspiro [4.4] nonane-6-ketone
CN111348992A (en) Novel method for synthesizing 1-bromo-2, 2-dimethoxypropane
CN111848423A (en) Preparation method of tert-butyl 3-oxocyclobutylcarbamate
CN101481334A (en) Rivastigmine preparation suitable for industrial production
CN113024479A (en) Preparation method of clomazone
CN108658845B (en) Preparation method of deuterated intermediate
CN110407902B (en) Method for removing 17-acetoxyl group from steroid compound
CN109851518A (en) The preparation method of the aceted intermediate of the fluoro- 3- methyl isobenzofuran -3- ketone of one kind (S) -5-
CN105272905B (en) A kind of piperidine compounds and preparation method thereof
CN114478407B (en) Preparation method and application of chiral homopiperazine and derivatives thereof
CN114315494B (en) Preparation method of (S) -2-methylazetidine hydrochloride

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB03 Change of inventor or designer information

Inventor after: Wu Simin

Inventor after: Tan Wenfei

Inventor after: Yao Qingjia

Inventor after: Xu Yangjun

Inventor before: Yao Qingjia

Inventor before: Wu Simin

Inventor before: Xu Yangjun

CB03 Change of inventor or designer information
GR01 Patent grant
GR01 Patent grant
PE01 Entry into force of the registration of the contract for pledge of patent right

Denomination of invention: Preparation method of indenyl amine compound

Effective date of registration: 20190926

Granted publication date: 20190122

Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd.

Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD.

Registration number: Y2019120000007

PE01 Entry into force of the registration of the contract for pledge of patent right
PC01 Cancellation of the registration of the contract for pledge of patent right

Date of cancellation: 20200910

Granted publication date: 20190122

Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd.

Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) Co.,Ltd.

Registration number: Y2019120000007

PC01 Cancellation of the registration of the contract for pledge of patent right
PE01 Entry into force of the registration of the contract for pledge of patent right

Denomination of invention: A preparation method of indenyl amine compound

Effective date of registration: 20201026

Granted publication date: 20190122

Pledgee: Tianjin SME Credit Financing Guarantee Center

Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) Co.,Ltd.

Registration number: Y2020120000021

PE01 Entry into force of the registration of the contract for pledge of patent right
PC01 Cancellation of the registration of the contract for pledge of patent right

Granted publication date: 20190122

Pledgee: Tianjin SME Credit Financing Guarantee Center

Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD.

Registration number: Y2020120000021

PC01 Cancellation of the registration of the contract for pledge of patent right