CN110229067A - A kind of 2- amino indenes preparation method - Google Patents
A kind of 2- amino indenes preparation method Download PDFInfo
- Publication number
- CN110229067A CN110229067A CN201910494122.3A CN201910494122A CN110229067A CN 110229067 A CN110229067 A CN 110229067A CN 201910494122 A CN201910494122 A CN 201910494122A CN 110229067 A CN110229067 A CN 110229067A
- Authority
- CN
- China
- Prior art keywords
- preparation
- amino indenes
- indenes
- amino
- acid
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
- C07C209/26—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds by reduction with hydrogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Abstract
The present invention relates to a kind of synthetic routes that 2- amino indenes is new, using 2- indone as raw material, synthesize 2- amino indenes through one pot reaction high yield.2- amino indenes preparation method provided by the invention be a kind of high yield, low cost, environmental protection, it is easy to operate, be suitable for industrialized preparation method.
Description
Technical field
The present invention relates to pharmaceutical chemistry synthesis technical fields, and in particular to a kind of 2- amino indenes preparation method.
Background technique
2- amino indenes is important medicine intermediate, can be used as the intermediate and branch of the synthesis of antihypertensive Delapril
The synthesis material of trachea expanding agent datro occupys an important position in medical synthesis field.The method reported at present has
Seven kinds, analyze as follows various methods there are the problem of:
1.JP04124161 discloses the synthetic method for reporting a kind of 2- amino indenes, as shown in Fig. 2, wherein with the 1- being easy to get
Indone is raw material, introduces oxime at carbonyl ortho position, then be reduced into corresponding target product.But oxime is introduced at carbonyl ortho position
When, nitrous acid straight butyl is used, it is expensive, it is not easy to maintain, it is extremely unstable, be not suitable for industrialized production.
2.Rosen et al. is reacted using 2- indone as raw material with hydroxylamine hydrochloride in J.Org.Chem, 1963,28,2797 reports
2- indanone oxime is generated, then hydrogenating reduction produces 2- aminoidan.As shown in Fig. 3, main problem existing for the route is
Two step hydro-reduction yields are lower, and only 36.8%, product quality is poor, and purification process is difficult.
3.Masahide Yasuda et al. is original with indenes in J.Org.Chem, the synthetic method of 2003,68,7618 reports
Material, under the action of photoinitiator, one-step synthesis target product.It is light-initiated although synthetic route is shorter as described in attached drawing 4
Agent is not easy to obtain, and light reaction equipment is more difficult to seek, while there is also security risks, are not easy to industrialized production.
4.Didier Roche et al. in Org.Process.Res.Dev, 2001,5,167 reports using ninhydrin as raw material,
It reacts to obtain oxime with hydroxylamine hydrochloride in acid condition, then hydrogenation obtains target compound.As shown in Fig. 5, this conjunction
At method the problem is that ninhydrin price is higher, the disadvantages of second step oximate waste water is more, and gross production rate is lower.
5.Goksu et al. occurs using 2- indanol as raw material with hydrazoic acid in Tetrahedron, 2005,61,6801 reports
Mitsunobu reacts to obtain azido compound, and then hydro-reduction obtains target compound.As shown in Fig. 6, the synthetic method
The problem is that 2- indanol is not easy to obtain, hydrazoic acid toxicity is very big, and the intermediate azido compound of generation has risk of explosion.
6. using 1- indone as raw material, by reacting with cuprous bromide, then Cao Shenghua et al. is reported in CN104945265A
Then hydro-reduction reacts to obtain target compound with potassium phthalimide.As shown in Fig. 7, existing for the route
The disadvantages of problem higher cost, yield is low, and side reaction is more.
7. Yang Kai et al. is reported in CN109438253A generates 2- by raw material and cyan-acetic ester reaction of adjacent benzyl dichloride
Cyano indenes, then hydrolysis generates 2- indane formamide, and last Hofmann degradation reaction generates target compound.Such as 8 institute of attached drawing
Show, the disadvantages of the disadvantages of this method step is longer, and yield is lower, and wastewater flow rate is more.
Summary of the invention
In order to overcome the problems, such as that above method exists, a kind of 2- amino indenes preparation method is provided.
A kind of 2- amino indenes preparation method, comprising the following steps:
2- indone, benzylamine, solvent and acid are added in autoclave, palladium-carbon catalyst is added, is passed through hydrogen to certain pressure,
Temperature reaction, after reaction filters pressing, filtrate concentration, rectifying obtain product.
Preferably, acid described in step 1 is glacial acetic acid, p-methyl benzenesulfonic acid；The solvent is methanol, ethyl alcohol, isopropyl
Alcohol, tetrahydrofuran, ethyl acetate.
Preferably, the molar equivalent of palladium-carbon catalyst described in step 1 is 5~10mol%.
Preferably, pressure limit described in step 1 is 2~4Mpa；The temperature reaction temperature is 30-900C.
The beneficial effects of the present invention are:
(1) synthetic route is redesigned, has found a kind of synthetic route that 2- amino indenes is new, using 2- indone as raw material,
2- amino indenes is synthesized through one pot reaction high yield.
(2) 2- amino indenes preparation method provided by the invention be a kind of high yield, low cost, environmental protection, it is easy to operate, be suitable for work
The preparation method of industry.
Detailed description of the invention
Fig. 1 is 2- of embodiment of the present invention amino indenes preparation method route map；
Fig. 2 is the synthetic line figure of prior art 2- amino indenes；
Fig. 3 is the synthetic line figure of prior art 2- amino indenes；
Fig. 4 is the synthetic line figure of prior art 2- amino indenes；
Fig. 5 is the synthetic line figure of prior art 2- amino indenes；
Fig. 6 is the synthetic line figure of prior art 2- amino indenes；
Fig. 7 is the synthetic line figure of prior art 2- amino indenes；
Fig. 8 is the synthetic line figure of prior art 2- amino indenes.
Specific embodiment
With reference to embodiments, the technical solution in the present invention is clearly and completely described.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
Embodiment 1
132g 2- indone, 128g benzylamine, 450ml ethyl alcohol and 5ml glacial acetic acid are added in autoclave, 15g palladium carbon is added and urges
Agent is passed through hydrogen to 3Mpa, and 80 DEG C are reacted, filters pressing after reaction, and filtrate concentration, rectifying obtains 121g product, yield:
91%.
Embodiment 2
120g 2- indone, 115g benzylamine, 420ml methanol and 3ml glacial acetic acid are added in autoclave, 12g palladium carbon is added and urges
Agent is passed through hydrogen to 2Mpa, and 80 DEG C are reacted, filters pressing after reaction, and filtrate concentration, rectifying obtains 110g product, yield:
90%.
Embodiment 3
150g 2- indone, 145g benzylamine, 600ml isopropanol and 8ml glacial acetic acid are added in autoclave, 20g palladium carbon is added
Catalyst is passed through hydrogen to 3Mpa, and 80 DEG C are reacted, filters pressing after reaction, and filtrate concentration, rectifying obtains 140g product, yield:
93%.
The above described is only a preferred embodiment of the present invention, be not intended to limit the scope of the present invention,
Therefore all technical solutions formed using equivalent substitution or equivalent transformation, it falls within the scope of protection required by the present invention.
Claims (4)
1. a kind of 2- amino indenes preparation method, which comprises the following steps:
2- indone, benzylamine, solvent and acid are added in autoclave, palladium-carbon catalyst is added, is passed through hydrogen to certain pressure, heating
Reaction, after reaction filters pressing, filtrate concentration, rectifying obtain product.
2. a kind of 2- amino indenes preparation method according to claim 1, it is characterised in that: acid described in step 1 is ice
Acetic acid, p-methyl benzenesulfonic acid；The solvent is methanol, ethyl alcohol, isopropanol, tetrahydrofuran, ethyl acetate.
3. a kind of 2- amino indenes preparation method according to claim 1, it is characterised in that: palladium carbon described in step 1 is urged
The molar equivalent of agent is 5~10mol%.
4. a kind of 2- amino indenes preparation method according to claim 1, it is characterised in that: pressure model described in step 1
It encloses for 2~4Mpa；The temperature of the temperature reaction is 30-90 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910494122.3A CN110229067A (en) | 2019-06-05 | 2019-06-05 | A kind of 2- amino indenes preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910494122.3A CN110229067A (en) | 2019-06-05 | 2019-06-05 | A kind of 2- amino indenes preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110229067A true CN110229067A (en) | 2019-09-13 |
Family
ID=67859385
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910494122.3A Pending CN110229067A (en) | 2019-06-05 | 2019-06-05 | A kind of 2- amino indenes preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110229067A (en) |
Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995018617A1 (en) * | 1994-01-10 | 1995-07-13 | Teva Pharmaceutical Industries Ltd. | 1-aminoindan derivatives and compositions thereof |
| CN101260048A (en) * | 2008-04-15 | 2008-09-10 | 苏州凯达生物医药技术有限公司 | Method for preparing rasagiline |
| US20080287676A1 (en) * | 2003-06-12 | 2008-11-20 | Abbott Laboratories | Fused compounds that inhibit vanilloid receptor subtype 1 (vr1) receptor |
| CN101379061A (en) * | 2006-02-02 | 2009-03-04 | 千禧药品公司 | Inhibitors of E1 activating enzyme |
| CN101516850A (en) * | 2006-08-08 | 2009-08-26 | 米伦纽姆医药公司 | Heteroaryl compounds useful as inhibitors of E1 activating enzymes |
| CN102718663A (en) * | 2012-06-21 | 2012-10-10 | 台州市华南医化有限公司 | Synthesis method of 5-chloro-1-indene amine |
| CN103608347A (en) * | 2011-05-30 | 2014-02-26 | 安斯泰来制药株式会社 | Imidazopyridine compound |
| CN104349775A (en) * | 2012-06-14 | 2015-02-11 | 伊莱利利公司 | Inhibitor of jak1 and jak2 |
| CN104395310A (en) * | 2012-05-09 | 2015-03-04 | 拜耳药业股份公司 | Bicyclically substituted uracils and the use thereof |
| CN104628575A (en) * | 2015-02-09 | 2015-05-20 | 许昌豪丰化学科技有限公司 | Preparation method of 2-aminoindan |
| CN104945265A (en) * | 2015-06-09 | 2015-09-30 | 成都大学 | Synthetic method for indan-2-amine |
| CN105175270A (en) * | 2015-08-31 | 2015-12-23 | 吴玲 | Preparation method for R-5-trifluoromethyl-1-aminoindane |
| CN105884626A (en) * | 2016-05-04 | 2016-08-24 | 龙曦宁（上海）医药科技有限公司 | Synthesis method of 2-aminoindane derivative and product of 2-aminoindane derivative |
| CN106431939A (en) * | 2016-09-11 | 2017-02-22 | 陈永军 | Method for synthesizing R type aminoindane |
| CN109369417A (en) * | 2018-10-19 | 2019-02-22 | 诚达药业股份有限公司 | A kind of preparation method of 2- aminoidan derivatives |
| CN109438253A (en) * | 2018-10-08 | 2019-03-08 | 江苏苏利精细化工股份有限公司 | A kind of method of novel synthesis 2- amino indenes |
| WO2019058290A1 (en) * | 2017-09-20 | 2019-03-28 | Suven Life Sciences Limited | Improved process for the preparation of ozanimod α-amino compound |
-
2019
- 2019-06-05 CN CN201910494122.3A patent/CN110229067A/en active Pending
Patent Citations (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995018617A1 (en) * | 1994-01-10 | 1995-07-13 | Teva Pharmaceutical Industries Ltd. | 1-aminoindan derivatives and compositions thereof |
| EP0738149A1 (en) * | 1994-01-10 | 1996-10-23 | Teva Pharmaceutical Industries, Ltd. | 1-aminoindan derivatives and compositions thereof |
| US20080287676A1 (en) * | 2003-06-12 | 2008-11-20 | Abbott Laboratories | Fused compounds that inhibit vanilloid receptor subtype 1 (vr1) receptor |
| CN101379061A (en) * | 2006-02-02 | 2009-03-04 | 千禧药品公司 | Inhibitors of E1 activating enzyme |
| CN101516850A (en) * | 2006-08-08 | 2009-08-26 | 米伦纽姆医药公司 | Heteroaryl compounds useful as inhibitors of E1 activating enzymes |
| CN101260048A (en) * | 2008-04-15 | 2008-09-10 | 苏州凯达生物医药技术有限公司 | Method for preparing rasagiline |
| CN103608347A (en) * | 2011-05-30 | 2014-02-26 | 安斯泰来制药株式会社 | Imidazopyridine compound |
| CN104395310A (en) * | 2012-05-09 | 2015-03-04 | 拜耳药业股份公司 | Bicyclically substituted uracils and the use thereof |
| CN104349775A (en) * | 2012-06-14 | 2015-02-11 | 伊莱利利公司 | Inhibitor of jak1 and jak2 |
| CN102718663A (en) * | 2012-06-21 | 2012-10-10 | 台州市华南医化有限公司 | Synthesis method of 5-chloro-1-indene amine |
| CN104628575A (en) * | 2015-02-09 | 2015-05-20 | 许昌豪丰化学科技有限公司 | Preparation method of 2-aminoindan |
| CN104945265A (en) * | 2015-06-09 | 2015-09-30 | 成都大学 | Synthetic method for indan-2-amine |
| CN105175270A (en) * | 2015-08-31 | 2015-12-23 | 吴玲 | Preparation method for R-5-trifluoromethyl-1-aminoindane |
| CN105884626A (en) * | 2016-05-04 | 2016-08-24 | 龙曦宁（上海）医药科技有限公司 | Synthesis method of 2-aminoindane derivative and product of 2-aminoindane derivative |
| CN106431939A (en) * | 2016-09-11 | 2017-02-22 | 陈永军 | Method for synthesizing R type aminoindane |
| WO2019058290A1 (en) * | 2017-09-20 | 2019-03-28 | Suven Life Sciences Limited | Improved process for the preparation of ozanimod α-amino compound |
| CN109438253A (en) * | 2018-10-08 | 2019-03-08 | 江苏苏利精细化工股份有限公司 | A kind of method of novel synthesis 2- amino indenes |
| CN109369417A (en) * | 2018-10-19 | 2019-02-22 | 诚达药业股份有限公司 | A kind of preparation method of 2- aminoidan derivatives |
Non-Patent Citations (6)
| Title |
|---|
| ARIE L. GUTMAN等: "Stereo- and regioselectivity in asymmetric synthesis of a-amino substituted benzocyclic compounds", 《TETRAHEDRON: ASYMMETRY》 * |
| MARIA LAURA PATI等: "Deconstruction of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety to separate P-glycoprotein (P-gp) activity from s2 receptor affinity in mixed P-gp/s2 receptor agents", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| YAACOV HERZIG等: "Hydroxy-1-aminoindans and Derivatives: Preparation, Stability,and Reactivity", 《J. ORG. CHEM.》 * |
| 唐家邓等: "甲磺酸雷沙吉兰的合成", 《中国医药工业杂志》 * |
| 李磊等: "抗帕金森新药雷莎吉兰盐酸盐合成的改进", 《徐州师范大学学报(自然科学版)》 * |
| 沈宗旋等: "甲磺酸雷莎吉兰的合成", 《苏州大学学报(自然科学版)》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104447445A (en) | Preparation method for synthesizing apremilast intermediate | |
| CN102070575A (en) | New synthesis method of caronic anhydride | |
| CN100404497C (en) | Nitrile reducing process to prepare amine | |
| CN106432040B (en) | A kind of green synthesis method of medicine intermediate 5- bromo indole | |
| CN113024385B (en) | Preparation method of 2,2 '-bis (trifluoromethyl) -4, 4' -diaminobiphenyl | |
| CN110229067A (en) | A kind of 2- amino indenes preparation method | |
| CN102653517A (en) | Method for preparing isocyanate from carbamate | |
| CN102746161A (en) | Method for synthesizing 1,8-terpene diamine | |
| CN1683326A (en) | Process for producing methyl carbamate | |
| CN103497157B (en) | 2-imidazolidone synthesis method | |
| CN108530301B (en) | Synthetic method of 2,4, 6-trifluorobenzylamine | |
| CN104151183B (en) | A kind of preparation method of 4-acetyl aminomethyl methyl cyclohexanecarboxylaand | |
| CN101863777B (en) | Preparation method for solvent-free 2, 4-dimethylaniline and 2, 6-dimethylaniline | |
| CN111807968B (en) | Synthetic method of 2- (1-cyclohexenyl) ethylamine | |
| JPS5822100B2 (en) | Method for producing O-phenylenediamine | |
| CN112794803A (en) | Preparation method of cyclopropylamine intermediate methyl cyclopropanecarboxylate | |
| CN112500355A (en) | Preparation method of substituted uracil benzaldehyde | |
| CN103896903A (en) | Method for preparing and purifying 2,3-O-isopropylidene threitol | |
| CN112209839A (en) | Method for synthesizing 2, 2-difluoroethylamine by using high-boiling-point substance in R142b as raw material | |
| CN104672093B (en) | A kind of preparation method of bicyclo-propyl methylamine | |
| CN101492348A (en) | Method for producing 1-adamantane ethanol | |
| CN108947849A (en) | A kind of method of solvent-free catalytic hydrogenation production 2,4 difluorobenzene amine | |
| CN112521265B (en) | Method for continuously producing glycollic acid | |
| CN112441935B (en) | Synthesis method of beta-aminoketone compound | |
| CN112521350B (en) | Synthetic method of 3-methylamino tetrahydrofuran |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190913 |