CN105017211A - 2-phenyl propionic ester derivative and preparation method and application thereof - Google Patents
2-phenyl propionic ester derivative and preparation method and application thereof Download PDFInfo
- Publication number
- CN105017211A CN105017211A CN201410181199.2A CN201410181199A CN105017211A CN 105017211 A CN105017211 A CN 105017211A CN 201410181199 A CN201410181199 A CN 201410181199A CN 105017211 A CN105017211 A CN 105017211A
- Authority
- CN
- China
- Prior art keywords
- formula
- preparation
- compound
- ethyl
- reaction
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention provides a preparation method of antihistamine medicine A. A new intermediate compound shown in a formula I is prepared and can serve as a raw material for the medicine A. A preparation method of the compound in the formula I is shown as follows: a compound in a formula II and a compound in a formula III react under the catalysis of manganese dioxide and dipyridyl nickel bromide. See the formulas in the specification.
Description
Technical field
The present invention relates to a kind of method of synthesizing antihistamine drug, and new intermediate in synthetic method and preparation method thereof.
Background technology
In the preparation of antihistamine drug A, be to adopt through dimethylated benzene derivative (formula C) and benzimidizole derivatives (formula B) as raw material traditionally, after carrying out coupling, then be hydrolyzed.
As CN1176964 adopts in this way exactly:
But the benzene feedstock derivative formula C of the method needs, in advance through di-methylation, not easily obtain, and side reaction to be more.Therefore, be necessary to study a kind of new preparation method.
Summary of the invention
Final purpose of the present invention is the defect overcoming existing preparation antihistamine drug A method, adopts and the diverse route of traditional method.Direct object of the present invention synthesizes intermediate---the 2-phenylpropionic acid ester derivative of a kind of preparation antihistamine drug A newly, then be that antihistamine drug A prepared by raw material with this intermediate.
Design and synthesis of the present invention new compound type I, can be used as Intermediate Preparation antihistamine drug A.That is: adopt unmethylated raw material to carry out linked reaction, carry out a methylation reaction more afterwards.This addresses the problem the problem that prior art Raw not easily obtains.
The new intermediate compound of formula I that contriver obtains thus.
In formula I, the group of R is not limit, as long as the group can sloughed in hydrolysing step when synthesizing antihistamine drug A.
Preferably, R is selected from the alkyl of C1-C6 straight or branched alkyl, substituted or unsubstituted C3-C6 cycloalkyl, alkoxybenzyl, benzene replacement.
The key distinction of formula I and antihistamine drug A is: in the structure of formula I, the α position of carbonyl only has a methyl, and in medicine A structure, there are two methyl the α position of carbonyl; Formula I is a kind of ester, and medicine A is a kind of acid.Thus, formula I is carried out methylate and can antihistamine drug A be obtained after Ester hydrolysis.
Medicine A is prior art, but is difficult to obtain formula I from medicine A, because be difficult to by medicine A demethylation realize.Formula I is obtained by substitution reaction in the present invention.
The preparation method of formula I is: by formula II and formula III under the catalysis of Manganse Dioxide and dipyridyl nickelous bromide, reaction production I.
In formula, R as defined above; X1 with X2 is identical or not identical, is leavings group, as halogen.
This reaction is reaction with same mole in principle.But in real reaction, the consumption of raw material is not crucial, and formula II or formula III all can be excessive, do not affect the carrying out of reaction.The consumption of such as formula III can be 0.5-6 mole times of formula II.
The existence of reacting middle catalyst is comparatively crucial, but its consumption does not play a decisive role, as long as can meet, reaction is carried out.The consumption of such as catalyzer dipyridyl nickelous bromide can be 0.01-2 mole times of formula II consumption; The consumption of Manganse Dioxide can be 0.05-10 mole times of formula II compound amount.
Reaction can be carried out in aprotic polar organic solvent.As acetonitrile, DMF, methyl-sulphoxide, benzene, toluene, tetrahydrofuran (THF), ethers etc.The wherein preferred ether of ether solvent, methyl tertiary butyl ether or glycol dimethyl ether.
Temperature of reaction is not crucial.This reaction can occur at normal temperatures.The change of temperature can affect to some extent on the reaction times.
The raw material of preparation formula I is all easy to get:
Formula III and Manganse Dioxide all can be bought conveniently by commercial sources,
Formula II can be obtained by art methods (as reference Orjales, Aurelio; Bordell, Maravillas; Rubio, Victor Journal of Heterocyclic Chemistry, the method for 1995, vol.32, #3p.707-718).
(chemical formula is NiBr to dipyridyl nickelous bromide
2(bpy)
2, wherein bpy=2,2 '-dipyridyl) also can be obtained by art methods (as with reference to Inorg.Chem.2011,50,4553 – 4558).
One of purposes of formula I is as intermediate, for the preparation of a kind of antihistamine drug formula A: formula I carried out methylating and can obtaining this antihistamine drug A after Ester hydrolysis.
In the preparation process of medicine A, by introducing new intermediate formula I, methylation reaction being delayed and carries out, solving the problem that raw material not easily obtains, and make the preparation of medicine A easier.
The preparation of medicine A is with formula I for raw material, after first carrying out methylation reaction, then is hydrolyzed and is obtained by reacting.
(1) methylation reaction: with formula I for raw material, carries out reaction with methyl iodide in the basic conditions and generates methylate;
Described alkali is selected from sodium hydride, sodium hydroxide, potassium tert.-butoxide or potassium hydroxide;
In methylation reaction, the consumption of alkali is 1.2 ~ 3.0 moles times of formula I consumption, and the consumption of methyl iodide is 0.8 ~ 1.1 mole times of formula I consumption;
The temperature of methylation reaction controls between 0 ~ 30 DEG C
(2) hydrolysis reaction: after the methylate of formula I adds solvent, carry out back flow reaction to terminal under acid or alkaline conditions;
Described solvent is selected from the mixed solvent that one or both and water in tetrahydrofuran (THF), methyl alcohol, ethanol form;
Described alkali is highly basic, such as potassium hydroxide, lithium hydroxide or sodium hydroxide etc.;
Described acid is strong acid, such as hydrochloric acid, sulfuric acid etc.
Embodiment:
In following examples, product detects and uses HPLC method, and concrete chromatographic condition is:
Chromatographic column: octadecylsilane (150mm × 4.6mm5um)
Determined wavelength: 270nm
Moving phase: methyl alcohol: water=50:50
Sample introduction concentration: 200ug/ml
Column temperature: 30 DEG C
The synthesis of embodiment 1 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-methyl propionate
8.24g4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] chlorinated benzene is joined 200mlN, in dinethylformamide, add 2.12g dipyridyl nickelous bromide and 0.09g Manganse Dioxide (activated) again, the N containing 4.18g2-bromo propionic acid A ester is dripped under 100 DEG C of conditions, dinethylformamide solution, in 100 DEG C of insulation reaction after dropwising, HPLC method detects that wherein a kind of raw material is stopped reaction after disappearing.
Reacting liquid filtering, 300ml water and 200ml ethyl acetate is added in filtrate, layering, collected organic layer, concentrated, cross silica gel column chromatography (using methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-methyl propionate 5.10g.
Product nuclear magnetic data:
1HMNR(500MHz,CD3OD)1.05(t,3H),1.44(d,3H),2.00～2.14(m,4H),2.25～2.30(m,2H),2.63～2.67(m,2H),2.82～2.86(m,2H),3.18～3.20(m,3H),3.36～3.41(m,2H),3.64(s,3H),3.72～3.76(m,3H),4.43～4.45(m,2H),7.21～7.25(m,6H),7.47(d,1H),7.61(d,1H)。
The synthesis of embodiment 2 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-ethyl propionate
9.13g4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] bromobenzene is joined in 400ml acetonitrile, add 0.11g dipyridyl nickelous bromide and 0.87g Manganse Dioxide (activated), the acetonitrile solution containing 1.37g2-chloropropionic acid ethyl ester is dripped under 50 DEG C of conditions, in 50 DEG C of insulation reaction after dropwising, HPLC method detects that wherein a kind of raw material is stopped reaction after disappearing.
Reacting liquid filtering, 400ml water and 400ml ethyl acetate is added in filtrate, layering, collected organic layer, concentrated, cross silica gel column chromatography (using methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-ethyl propionate 3.82g.
Product nuclear magnetic data:
1HMNR(500MHz,CD3OD)1.06(t,3H),1.29(t,3H),1.45(d,3H),2.00～2.14(m,4H),2.25～2.30(m,2H),2.63～2.67(m,2H),2.82～2.86(m,2H),3.18～3.20(m,3H),3.36～3.41(m,2H),3.72～3.76(m,3H),4.02～4.21(m,2H),4.42～4.45(m,2H),7.21～7.25(m,6H),7.47(d,1H),7.62(d,1H)。
The synthesis of embodiment 3 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-isopropyl propionate
10.07g4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl-iodide is joined in 300ml glycol dimethyl ether, add 0.53g dipyridyl nickelous bromide and 0.17g Manganse Dioxide (activated), the ethylene glycol dimethyl ether solution containing 12.35g2-chloropropionic acid isopropyl ester is dripped under 20 DEG C of conditions, in 20 DEG C of insulation reaction after dropwising, HPLC method detects that wherein a kind of raw material is stopped reaction after disappearing.
Reacting liquid filtering, 200ml water and 300ml ethyl acetate is added in filtrate, layering, collected organic layer, concentrated, cross silica gel column chromatography (using methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-isopropyl propionate 6.88g.
Product nuclear magnetic data:
1HMNR(500MHz,CD3OD),1.10(t,3H),1.35(d,6H),1.29(t,3H),1.48(d,3H),2.00～2.14(m,4H),2.25～2.30(m,2H),2.63～2.67(m,2H),2.82～2.86(m,2H),3.18～3.20(m,3H),3.36～3.41(m,2H),3.72～3.76(m,3H),4.42～4.45(m,2H),4.20～4.39(m,1H),7.21～7.25(m,6H),7.47(d,1H),7.62(d,1H)。
Embodiment 4 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-propionic acid is to methoxybenzyl ester
8.24g4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] chlorinated benzene is joined in 500ml benzene, add 0.74g dipyridyl nickelous bromide and 1.74g Manganse Dioxide (activated), drip containing 32.77g2-bromo acid the benzole soln of methoxybenzyl ester under 80 DEG C of conditions, in 80 DEG C of insulation reaction after dropwising, HPLC method detects that wherein a kind of raw material is stopped reaction after disappearing.
Reacting liquid filtering, 500ml water and 500ml ethyl acetate is added in filtrate, layering, collected organic layer, concentrated, cross silica gel column chromatography (using methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-propionic acid to methoxybenzyl ester 7.29g.
The synthesis of embodiment 5 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-cyclohexyl propionate
8.24g4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] chlorinated benzene is joined in 200ml methyl-sulphoxide, add 5.31g dipyridyl nickelous bromide and 17.38g Manganse Dioxide (activated), the dimethyl sulfoxide solution containing 13.17g2-bromo acid cyclohexyl is dripped under 30 DEG C of conditions, in 30 DEG C of insulation reaction after dropwising, HPLC method detects that wherein a kind of raw material is stopped reaction after disappearing.
Reacting liquid filtering, 200ml water and 500ml ethyl acetate is added in filtrate, layering, collected organic layer, concentrated, cross silica gel column chromatography (using methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-cyclohexyl propionate 5.42g.
The synthesis of embodiment 6 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-benzyl propionate
9.13g4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] bromobenzene is joined in 340ml tetrahydrofuran (THF), add 10.62g dipyridyl nickelous bromide and 10.43g Manganse Dioxide (activated), the tetrahydrofuran solution containing 8.74g2-chloropropionic acid benzyl ester is dripped under 50 DEG C of conditions, in 50 DEG C of insulation reaction after dropwising, HPLC method detects that wherein a kind of raw material is stopped reaction after disappearing.
Reacting liquid filtering, 400ml water and 200ml ethyl acetate is added in filtrate, layering, collected organic layer, concentrated, cross silica gel column chromatography (using methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-benzyl propionate 6.26g.
Product nuclear magnetic data:
1HMNR(500MHz,CD3OD)1.10(t,3H),1.54(d,3H),2.00～2.17(m,4H),2.25～2.32(m,2H),2.63～2.69(m,2H),2.82～2.87(m,2H),3.18～3.20(m,3H),3.36～3.42(m,2H),3.73～3.79(m,3H),4.44～4.47(m,2H),5.27(s,2H),7.21～7.25(m,6H),7.33～7.41(m,3H),7.46～7.51(m,3H),7.69(d,1H)。
The synthesis of embodiment 7 medicine A
The chemical name of medicine A is (2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-2-rnethyl-propanoic acid), and structural formula is as follows:
1) methylation reaction: 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] the phenyl]-methyl propionate 0.6g obtained in Example 1, join 20ml N, in dinethylformamide, add 78mg sodium hydride again, stirred at ambient temperature is after 1 hour, drip 215mg methyl iodide again, room temperature reaction is stopped reaction after 4 hours.After adding 60ml water in reaction solution, be extracted with ethyl acetate three times, each 30ml, merge organic layer, concentrated, cross silica gel column chromatography (methylene dichloride: methyl alcohol=100:1 to 5:1 gradient elution), obtain 100mg methylate.
2) hydrolysis reaction: the sodium hydroxide solution adding 40ml tetrahydrofuran (THF), 40ml methyl alcohol and 40ml4mol/L in this methylate, back flow reaction is after 9 hours, stopped reaction.After revolving the organic solvent steamed in removing reaction solution, add 40ml water again, with salt acid for adjusting pH value to weakly acidic pH, with n-butanol extraction twice, each 40ml, united extraction liquid, washing, drying, concentrated, obtain product 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-2-rnethyl-propanoic acid 60mg.
Product nuclear magnetic data:
1HMNR(500MHz,CD3OD)1.07(t,J＝7.0Hz,3H),1.51(s,6H),2.18～2.24(m,4H),2.89～2.97(m,4H),3.08～3.11(m,2H),3.37～3.42(m,2H),3.59(d,J＝12.8Hz,2H),3.76(t,J＝4.8Hz,2H),4.49(t,J＝4.8Hz,2H),7.16(t,J＝8.0Hz,2H),7.24～7.29(m,2H),7.38(d,J＝8.0Hz,2H),7.50～7.63(m,2H)。
Claims (10)
1. the preparation method of antihistaminic class medicine A, is characterized in that, with formula I for raw material, first carrying out methylation reaction, then the reaction that is hydrolyzed, and obtains medicine A;
In formula, R is selected from C1-C6 straight or branched alkyl, substituted or unsubstituted C3-C6 cycloalkyl, alkoxybenzyl, or the alkyl that benzene replaces.
2. preparation method according to claim 1, described methylation reaction is that formula I carries out being obtained by reacting methylate with methyl iodide in the basic conditions, and described alkali is selected from sodium hydride, sodium hydroxide, potassium tert.-butoxide or potassium hydroxide; Described hydrolysis reaction is by above-mentioned methylate under acid or alkaline conditions, carries out back flow reaction.
3. preparation method according to claim 1, the preparation method of described formula I is: formula II compound and formula III compound react under the catalysis of Manganse Dioxide and dipyridyl nickelous bromide;
In formula, R is selected from C1-C6 straight or branched alkyl, substituted or unsubstituted C3-C6 cycloalkyl, alkoxybenzyl, or the alkyl that benzene replaces; X1 and X2 is leavings group, X1 with X2 is identical or not identical.
4. the preparation method described in claim 1 or 3, X1 and X2 is halogen.
5. the preparation method described in claim 1 or 3, the consumption of described formula III compound is 0.5-6 mole times of formula II compound amount.
6. the preparation method described in claim 1 or 3, the consumption of described dipyridyl nickelous bromide is 0.01-2 mole times of formula II compound amount.
7. the preparation method described in claim 1 or 3, the consumption of described Manganse Dioxide is 0.05-10 mole times of formula II compound amount.
8. compound shown in formula I:
In formula I, R is selected from C1-C6 straight or branched alkyl, substituted or unsubstituted C3-C6 cycloalkyl, alkoxybenzyl, or the alkyl that benzene replaces.
9. compound according to claim 8 is following arbitrary compound:
2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-methyl propionate,
2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-ethyl propionate,
2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-isopropyl propionate, or,
2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazolyl-2 radicals-Ji]-piperidino] ethyl] phenyl]-benzyl propionate.
10. compound described in claim 8 or 9 is preparing the application in antihistaminic class medicine A,
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410181199.2A CN105017211A (en) | 2014-04-30 | 2014-04-30 | 2-phenyl propionic ester derivative and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410181199.2A CN105017211A (en) | 2014-04-30 | 2014-04-30 | 2-phenyl propionic ester derivative and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105017211A true CN105017211A (en) | 2015-11-04 |
Family
ID=54407561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410181199.2A Pending CN105017211A (en) | 2014-04-30 | 2014-04-30 | 2-phenyl propionic ester derivative and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105017211A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017167949A1 (en) * | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
| CN111454150A (en) * | 2019-12-25 | 2020-07-28 | 南京工业大学 | Synthesis method of (S) -2-aryl propionate compound |
| CN113292534A (en) * | 2021-05-27 | 2021-08-24 | 常州大学 | Preparation method of bilastine key intermediate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1753670A (en) * | 2003-02-26 | 2006-03-29 | 科学研究和应用咨询公司 | Novel derivatives of benzimidazole and imidazo-pyridine and their use as medicaments |
| CN103351380A (en) * | 2013-06-30 | 2013-10-16 | 北京万全德众医药生物技术有限公司 | Preparation method of Bilastine |
| WO2014026657A2 (en) * | 2012-08-15 | 2014-02-20 | Zentiva, K.S | A process for the preparation of a derivative of 2-methyl-2'-phenylpropionic acid using new intermediates |
-
2014
- 2014-04-30 CN CN201410181199.2A patent/CN105017211A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1753670A (en) * | 2003-02-26 | 2006-03-29 | 科学研究和应用咨询公司 | Novel derivatives of benzimidazole and imidazo-pyridine and their use as medicaments |
| WO2014026657A2 (en) * | 2012-08-15 | 2014-02-20 | Zentiva, K.S | A process for the preparation of a derivative of 2-methyl-2'-phenylpropionic acid using new intermediates |
| CN103351380A (en) * | 2013-06-30 | 2013-10-16 | 北京万全德众医药生物技术有限公司 | Preparation method of Bilastine |
Non-Patent Citations (1)
| Title |
|---|
| MURIEL DURANDETTI ET AL.: "Ni-catalyzed activation of α-chloroesters: a simple method for the synthesis of α-arylesters and β-hydroxyesters", 《TETRAHEDRON》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017167949A1 (en) * | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
| CN111454150A (en) * | 2019-12-25 | 2020-07-28 | 南京工业大学 | Synthesis method of (S) -2-aryl propionate compound |
| CN111454150B (en) * | 2019-12-25 | 2023-03-28 | 南京工业大学 | Synthesis method of (S) -2-aryl propionate compound |
| CN113292534A (en) * | 2021-05-27 | 2021-08-24 | 常州大学 | Preparation method of bilastine key intermediate |
| CN113292534B (en) * | 2021-05-27 | 2022-04-26 | 常州大学 | Preparation method of bilastine key intermediate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Regioselective and stereoselective sulfonylation of alkynylcarbonyl compounds in water | |
| Jin et al. | Copper-catalysed addition of α-alkyl azaarenes to ethyl glyoxylate via direct C (sp 3)–H activation | |
| Zhao et al. | Rhodium (I)-catalyzed C6-selective C–H alkenylation and polyenylation of 2-pyridones with alkenyl and conjugated polyenyl carboxylic acids | |
| Krasovskiy et al. | Cross-couplings of alkyl halides with heteroaromatic halides, in water at room temperature | |
| Wang et al. | Room temperature, open-flask C–H arylation of electron-deficient heteroarenes with triazenes: rapid synthesis of heterobiaryls | |
| CN110204486B (en) | Synthesis method of quinoline derivative | |
| CN105017211A (en) | 2-phenyl propionic ester derivative and preparation method and application thereof | |
| CN110357842A (en) | A kind of fluoroalkyl substituted furan class compound and preparation method thereof | |
| Meshram et al. | Bismuthtriflate-catalyzed Reaction of N-Alkylisatins with Allyltrimethylsilane | |
| CN105272997B (en) | The compound of the propargyl containing difluoro, preparation method and application | |
| WO2016141840A1 (en) | Method synthesizing pharmaceutical intermediate phenanthrene compound in sodium hydroxide environment | |
| JP6096465B2 (en) | Method for preparing 2-alkoxy-5- (pyridin-2-yl) pyridine, an intermediate of peranpanel | |
| CN112645871B (en) | N-CF 2 H-1, 2-dihydroSynthesis method of pyridine-2-ketone compound | |
| CN102863371A (en) | Fluoro dihydropyrrole or fluoro pyrrole | |
| CN105693696A (en) | Aminopyrazolyldipyridine and preparation method thereof | |
| Chen et al. | Transition-metal-free highly efficient synthesis of 2-pyridones from β-keto amides and ynals | |
| CN105753725A (en) | Preparation method of enaminone compounds | |
| CN106938985A (en) | A kind of 5 amide groups quinolines of alkenyl 8 and its one-pot preparation thereof | |
| CN114957097B (en) | Preparation method of indoline compound | |
| CN102675204B (en) | Intermediate for synthesizing (I)-huperzine A, synthesis method and usage thereof | |
| CN109096181B (en) | Method for green synthesis of 2-sulfonylpyridine derivative under assistance of ultrasonic waves | |
| CN109336929A (en) | A kind of asymmetric P^N^P type ligand and preparation method thereof based on 2- amino tetrahydronaphthalenand pyridine | |
| Prater | Remote Enantioselective Functionalization of Alkenes via a Redox-Relay Strategy | |
| Huang et al. | Rapid modular synthesis of indole ethers via dehydrogenative cross-coupling reaction of indoles and alcohols | |
| CN103483337B (en) | Fluorinated isoquinoline [a] pyrrole compounds and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | 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: 20151104 |