CN103408450A - Method for catalytically synthesizing tamibarotene through acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound - Google Patents
Method for catalytically synthesizing tamibarotene through acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound Download PDFInfo
- Publication number
- CN103408450A CN103408450A CN2013102611679A CN201310261167A CN103408450A CN 103408450 A CN103408450 A CN 103408450A CN 2013102611679 A CN2013102611679 A CN 2013102611679A CN 201310261167 A CN201310261167 A CN 201310261167A CN 103408450 A CN103408450 A CN 103408450A
- Authority
- CN
- China
- Prior art keywords
- tamibarotene
- palladium chloride
- acenaphthene
- allyl palladium
- heterocyclic carbine
- 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
Links
Images
Abstract
The invention belongs to the technical field of medicine pharmaceutical synthesis, and particularly relates to a method for catalytically synthesizing tamibarotene through an acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound, aiming at providing a novel synthesis method of tamibarotene. The method comprises the following steps of: by taking a novel acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound with high catalytic activity as a catalyst; performing amide carbonylation coupled reaction under carbon monoxide in order to directly synthesize a key precursor of tamibarotene by such one step; and then simply hydrolyzing to obtain the target compound, namely, tamibarotene. According to the method, the catalyst adopted has high catalytic performance, so that the catalytic coupling reaction brings high yield; and the catalyst is naturally easily synthesized, the raw materials adopted in the synthetic line are easily available, so that such synthetic line has high competitive advantages and high utility value in industrial production.
Description
Technical field
The invention belongs to technical field of medicine synthesis, be specifically related to the novel acenaphthene of a kind of use imidazoles N-heterocyclic carbine allyl palladium chloride compound as catalyzer, the novel method that the catalysis Tamibarotene is synthetic.
Background technology
Tamibarotene, English name: tamibarotene, (structural formula
1); chemistry 4-[(5 by name, 6,7; 8-tetrahydrochysene-5; 5,8,8-tetramethyl--2-naphthyl) carbamyl] phenylformic acid; a kind of new Retinoic Acid Receptor Alpha (retinoic acid receptor α; RAR α) agonist, as the treatment relapsed or stubborn new drug of impatient property promyelocytic leukemia (APL) of healing, and have certain potential antitumour activity by Nippon Shinyaku Co., Ltd. (JP) Tokyo To, Japan (Nippon Shinyaku) exploitation.In Japanese Initial Public Offering, commodity are called Amnolake in June, 2005.This product show ATRA is alleviated after the APL of recurrence have remarkable validity, this medical instrument effective in cure good, be difficult for developing immunity to drugs, the advantage such as untoward reaction is little.
The synthetic route of Tamibarotene mainly contains at present:
Route one be take the route be published in " Chinese Journal of Pharmaceuticals " the 1st phase of 40 volumes in 2009 one piece of document and is representative: with 2,5-dimethyl-2, the 5-hexylene glycol is initial feed, through chloro; Friedel-Crafts closes ring, obtains 1,2,3; 4-tetrahydrochysene-1, Isosorbide-5-Nitrae, 4-tetramethyl-naphthalene; nitrated through nitric acid, sulfuric acid, then hydro-reduction obtains 5,6,7; 8-tetrahydrochysene-5,5,8; 8-tetramethyl--2-naphthylamines, then with to the chloroformyl methyl benzoate react, and obtains Tamibarotene finally by hydrolysis.
Route two be take the synthetic route that patent documentation WO9114673 announces and is representative: equally with 2,5-dimethyl-2, the 5-hexylene glycol is initial feed; through chloro, with the Acetanilide Friedel-Crafts, close ring, obtain 2-kharophen 5; 5; 8,8-tetramethyl--5,6; 7; the 8-naphthane, then with to the chloroformyl methyl benzoate carry out the acyl permutoid reaction under five phosphonium chlorides exist, obtain Tamibarotene finally by hydrolysis.
Route three is thought the synthetic route that patent documentation CN101121675 announces: take aniline and the chloroformyl methyl benzoate is to initial feed; through esterification, obtain the aniline acyl radical methyl benzoate; then with 2; 5-bis-chloro-2; the 5-dimethyl carries out Friedel-Crafts and closes ring, obtains Tamibarotene finally by hydrolysis.
Route four is synthetic routes that patent documentation CN102633673 announces; it and route three are very similar; its difference is take that aniline and terephthalic acid monomethyl ester are starting raw material; under the effect of the condensing agents such as DCC/HOBt, generate the aniline acyl radical methyl benzoate; then with 2; 5-dimethyl-2,5-hexylene glycol are carried out Friedel-Crafts and are closed ring, obtain Tamibarotene finally by hydrolysis.
All there is certain shortcoming in above synthetic route:
1) synthetic route is longer, generally needs the reaction of four to five steps just can obtain the ultimate aim compound;
2) in synthetic, need repeatedly to use the strategy of protection and deprotection, Atom economy is poor;
3) the synthetic middle operations such as low temperature of using make synthesis step complicated, are unfavorable for industrial production;
4) in synthetic, repeatedly use concentrated hydrochloric acid, the reagent such as five phosphonium chlorides, by product is more, larger to the pollution of environment, does not meet the concept of environmental protection;
5) yield of some reaction is lower, and raw material (as to the chloroformyl methyl benzoate) is somewhat expensive and more difficult synthetic, has increased the Financial cost of synthetic route.
Above these shortcomings have all limited the application of existing synthetic route in industry to a certain extent.Therefore the method for existing synthetic Tamibarotene requires further improvement.
Summary of the invention
The objective of the invention is to propose a kind of new synthetic method of Tamibarotene, namely use a kind of novel acenaphthene of high catalytic activity imidazoles N-heterocyclic carbine allyl palladium chloride compound as catalyzer, aminocarboxyl linked reaction by carbon monoxide, one step is the key precursor of synthetic Tamibarotene directly, then can obtain the target compound Tamibarotene through simple hydrolysis.
The catalyzer that the aminocarboxyl linked reaction proposed in the present invention is used is a kind of novel acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride compound of high catalytic activity, and its chemical formula is C
40H
45ClN
2Pd, its concrete structure formula is as follows:
Novel acenaphthene used in the present invention imidazoles N-heterocyclic carbine allyl palladium chloride compound
1The preparation synthetic method specific as follows:
Under condition of nitrogen gas, add acenaphthene benzimidazole salt hydrochlorate (2.1 mmol, 2.1 eq.) in the bottle of 50 mL, allyl palladium chloride dimer (1.0 mmol, 1.0 eq.), potassium tert.-butoxide (2.5 mmol, 2.5 eq.) and tetrahydrofuran (THF) (24 mL, 0.042 mol/L).At room temperature stirring reaction is 24 hours, and removal of solvent under reduced pressure, by column chromatography for separation, obtains novel acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer after vacuum-drying
1.Its reaction formula is as follows:
。
Wherein, corresponding acenaphthene benzimidazole salt hydrochlorate structural formula is shown in upper reaction formula, [Pd (allyl) Cl]
2The allyl palladium chloride dimer, KO
t-Bu is potassium tert.-butoxide, and THF is tetrahydrofuran (THF), and r.t. is room temperature.
It is as follows that the present invention proposes the new synthetic method route of Tamibarotene, and concrete steps are:
1) under condition of nitrogen gas, acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1Catalysis 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine and the reaction of 4-Iodobenzoic acid ethyl ester generation aminocarboxyl, obtain 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] ethyl benzoate, specific operation process is as follows,
Under condition of nitrogen gas, in the round-bottomed flask of 50 mL, add potassiumphosphate (3.5 mmol) successively, acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1(1 mol%), 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine (2.61 mmol), 4-Iodobenzoic acid ethyl ester (0.87 mmol) and toluene (6 mL).Logical CO (carbon monoxide converter) gas, in reaction mixture 30 seconds, is put into reaction flask in oil bath, is heated to 90 degree reaction 19 hours.In reaction process, with the carbon monoxide balloon, keeping the gaseous tension in reaction flask is a normal atmosphere.After reaction finishes, removal of solvent under reduced pressure, column chromatography for separation, after vacuum-drying, obtain white solid;
2) 4-[(5,6,7,8-tetrahydrochysene-5,5,8; 8-tetramethyl--2-naphthyl) carbamyl] ethyl benzoate carries out an one-step hydrolysis, obtains 4-[(5,6,7,8-tetrahydrochysene-5,5; 8,8-tetramethyl--2-naphthyl) carbamyl] phenylformic acid, i.e. Tamibarotene, specific operation process is as follows
In reaction flask, add 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] ethyl benzoate (1 mmol), sodium hydroxide (2.5 mmol), methyl alcohol 2.5 mL and water 1.0 mL.Heating reflux reaction 3 hours, the TLC monitoring reaction finishes.To react cool to room temperature, under agitation, with salt acid for adjusting pH to 3 left and right of 1 mole, the adularescent solid generates, and suction filtration goes out solid, obtains white powder by washed with dichloromethane, is Tamibarotene.
The advantage of the new synthetic method of the Tamibarotene proposed in the present invention has:
1) synthetic route is short, only needs two steps just can obtain the target compound Tamibarotene, and namely 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine and 4-Iodobenzoic acid ethyl ester are at catalyzer
1Under catalysis, carbon monoxide occurs and insert, by the aminocarboxyl reaction, direct one-step synthesis Tamibarotene key intermediate, then obtain Tamibarotene through simple hydrolysis.
2) the synthetic route Atom economy is better.Repeatedly protection and deprotection strategy have been avoided.
3) avoided using difficult synthetic raw materials such as chloroformyl methyl benzoate, avoided some pungency acyl chlorides and acidic wastes, met the concept of environmental protection.
4) synthesis material cheaply is easy to get, and every step reaction yield is all very high, has reduced the Financial cost of synthetic route.
5) in synthetic route, utilize the source of carbon monoxide as carbonyl, be conducive to the protection of environment.
6) although in reaction, used acenaphthene the imidazoles N-heterocyclic carbine allyl palladium chloride of precious metal
1For catalyzer, the scope of the add-on of acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer can be at 0.5 mol% between 1.0 mol%, but, because its catalytic performance is high, make catalysis linked reaction have a very high yield, add catalyzer itself and be easy to synthesize, and the raw material in this synthetic route cheaply is easy to get, thereby this synthetic route still has very large competitive edge and industrial production utility value.
The accompanying drawing explanation
Fig. 1 is the prepared novel acenaphthene of embodiment 1 imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1The high resolution mass spectrum analysis chart.
Fig. 2 is the prepared 4-[(5 of embodiment 2,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] the proton nmr spectra analysis chart of ethyl benzoate.
Fig. 3 is the prepared 4-[(5 of embodiment 2,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] the carbon-13 nmr spectra analysis chart of ethyl benzoate.
Fig. 4 is the prepared 4-[(5 of embodiment 2,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] the high resolution mass spectrum analysis chart of ethyl benzoate.
Fig. 5 is the prepared 4-[(5 of embodiment 4,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] benzoic proton nmr spectra analysis chart.
Fig. 6 is the prepared 4-[(5 of embodiment 4,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] benzoic high resolution mass spectrum analysis chart.
Embodiment
Below by embodiment, further specifically describe the present invention, the present invention is not limited to following embodiment.
Embodiment 1:Novel acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1Preparation:
Under condition of nitrogen gas, in the round-bottomed flask of 50 mL, add acenaphthene benzimidazole salt hydrochlorate (1.26 g, 2.3 mmol) successively, allyl palladium chloride dimer (0.4 g, 1.1 mmol), potassium tert.-butoxide (0.31 g, 2.7 mmol) and tetrahydrofuran (THF) (24 mL).Stirring reaction is 24 hours under room temperature, removal of solvent under reduced pressure, and column chromatography for separation, after vacuum-drying, obtain yellow solid, is acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1.Productive rate: 1.35 g, 88%.
Nmr analysis:
1H NMR (CDCl
3, 400 MHz, 298 K): δ=7.69 (d,
J=8.4 Hz, 2H), 7.54 (t,
J=8.0 Hz, 2H), 7.39 – 7.32 (m, 6H), 6.84 (d,
J=6.8 Hz, 2H), 4.97 – 4.87 (m, 1H), 3.98 (d,
J=7.2 Hz, 1H), 3.37 – 3.27 (m, 3H), 3.16 – 3.10 (m, 2H), 2.90 (d,
J=13.2 Hz, 2H), 1.86 (d,
J=11.6 Hz, 1H), 1.37 (d,
J=7.0 Hz, 12H), 0.96 (dd,
J=12.4,6.4 Hz, 12H);
13C NMR (CDCl
3, 100 MHz, 298 K)=192.89,146.33,146.16,140.31,134.56,130.18,129.83,129.59,127.74,127.28,126.21,124.40,124.14,121.57,114.44,73.54,50.25,28.67,28.63,25.59,25.31,23.78,23.26.
Mass spectroscopy: HR-MS (ESI):
m/z659.2618 (calcd, [M-Cl]
+); 659.2633 (found, [M-Cl]
+).
Embodiment 2:4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] preparation () of ethyl benzoate:
Under condition of nitrogen gas, in the round-bottomed flask of 50 mL, add potassiumphosphate (0.741 g, 3.5 mmol) successively, acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1(0.006 g, 1 mol%), 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine (0.53 g, 2.61 mmol), 4-Iodobenzoic acid ethyl ester (0.241 g, 0.87 mmol) and toluene (6 mL).Logical CO (carbon monoxide converter) gas, in reaction mixture 30 seconds, is put into reaction flask in oil bath, is heated to 90 degree reaction 19 hours.In reaction process, with the carbon monoxide balloon, keeping the gaseous tension in reaction flask is a normal atmosphere.After reaction finishes, removal of solvent under reduced pressure, column chromatography for separation, after vacuum-drying, obtain white solid, is 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] ethyl benzoate.Productive rate: 0. 328 g, 99%.
Nmr analysis:
1H NMR (CDCl
3, 400 MHz, 298 K): δ=8.14 (d,
J=8.4 Hz, 2H), 7.92 (d,
J=8.0 Hz, 2H), 7.81 (s, 1H), 7.53 (brs, 1H), 7.44 (dd,
J=8.4 Hz,
J=1.6 Hz, 1H), 7.32 (d,
J=8.4 Hz, 1H), 4.41 (q,
J=7.2 Hz, 2H), 1.69 (s, 4H), Isosorbide-5-Nitrae 2 (t,
J=7.2 Hz, 3H), 1.29 (d,
J=8.0 Hz, 12H);
13C NMR (CDCl
3, 100 MHz, 298 K): δ=165.76,164.76,145.85,141.77,138.95,135.00,133.19,129.92,127.29,127.00,118.22,118.15,61.41,34.97,34.42,34.00,31.79,14.27.
Mass spectroscopy: HR-MS (ESI):
m/z402.2045 (calcd, [M+Na]
+); 402.2038 (found, [M+Na]
+).
Infrared analysis: IR (KBr): ν=3435,2956,1717,1651,1613,1537,1491,1407,1275,1108 cm
-1.
Wherein, the preparation method of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine can be with reference to the description of " pharmacy practice magazine " the 4th phase of 30 volumes in 2012 " improvement in synthesis of Tamibarotene ".
Embodiment 3:4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] preparation (two) of ethyl benzoate:
Under condition of nitrogen gas, in the round-bottomed flask of 200 mL, add potassiumphosphate (8.5 g, 40 mmol) successively, acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer
1(0.068 g, 1 mol%), 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine (6.08 g, 29.9 mmol), 4-Iodobenzoic acid ethyl ester (2.76 g, 10 mmol) and toluene (70 mL).Logical CO (carbon monoxide converter) gas, in reaction mixture 1 minute, is put into reaction flask in oil bath, is heated to 90 degree reaction 24 hours.In reaction process, with the carbon monoxide balloon, keeping the gaseous tension in reaction flask is a normal atmosphere.After reaction finished, column chromatography for separation, after vacuum-drying, obtained white solid, is 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] ethyl benzoate.Productive rate: 3.34 g, 92%.
Nmr analysis:
1H NMR (CDCl
3, 400 MHz, 298 K): δ=8.14 (d,
J=8.4 Hz, 2H), 7.92 (d,
J=8.0 Hz, 2H), 7.81 (s, 1H), 7.53 (brs, 1H), 7.44 (dd,
J=8.4 Hz,
J=1.6 Hz, 1H), 7.32 (d,
J=8.4 Hz, 1H), 4.41 (q,
J=7.2 Hz, 2H), 1.69 (s, 4H), Isosorbide-5-Nitrae 2 (t,
J=7.2 Hz, 3H), 1.29 (d,
J=8.0 Hz, 12H);
13C NMR (CDCl
3, 100 MHz, 298 K): δ=165.76,164.76,145.85,141.77,138.95,135.00,133.19,129.92,127.29,127.00,118.22,118.15,61.41,34.97,34.42,34.00,31.79,14.27.
Mass spectroscopy: HR-MS (ESI):
m/z402.2045 (calcd, [M+Na]
+); 402.2038 (found, [M+Na]
+).
Infrared analysis: IR (KBr): ν=3435,2956,1717,1651,1613,1537,1491,1407,1275,1108 cm
-1.
Embodiment 4:4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] phenylformic acid, the i.e. preparation of Tamibarotene:
In reaction flask, add 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] ethyl benzoate (379.5 mg, 1 mmol), sodium hydroxide (110 mg, 2.5 mmol), methyl alcohol 2.5 mL and water 1.0 mL.Heating reflux reaction 3 hours, the TLC monitoring reaction finishes.To react cool to room temperature, under agitation, with salt acid for adjusting pH to 3 left and right of 1 mole, the adularescent solid generates, and suction filtration goes out solid, obtains white powder by washed with dichloromethane, is Tamibarotene.Productive rate: 316 mg, 90%.
Nmr analysis:
1H NMR (DMSO-D
6, 400 MHz, 298 K): δ=13.28 (brs, 1H), 10.26 (brs, 1H), 8.08-8.03 (m, 4H), 7.68 (s, 1H), 7.58 (d,
J=8.8 Hz, 1H), 7.29 (d,
J=8.8 Hz, 1H), 1.64 (s, 4H), 1.24 (s, 12H), 1.23 (s, 12H).
Mass spectroscopy: HR-MS (ESI):
m/z374.1732 (calcd, [M+Na]
+); 374.1728 (found, [M+Na]
+).
Infrared analysis: IR (KBr): ν=3418,2960,1698,1655,1611,1589,1531,1503,1459,1407,1363,1286 cm
-1.
Claims (2)
1. the method for the synthetic Tamibarotene of an acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride compound for catalysis is characterized in that step is as follows:
(1) under condition of nitrogen gas, acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyst 5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthylamines and 4-Iodobenzoic acid ethyl ester generation carbonyl amination reaction, obtain 4-[(5,6,7,8-tetrahydrochysene-5,5,8,8-tetramethyl--2-naphthyl) carbamyl] ethyl benzoate, the scope of the add-on of acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer is: 0.5 mol% to 1.0 mol%;
(2) 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] ethyl benzoate carries out an one-step hydrolysis, obtains 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2) carbamyl] phenylformic acid, i.e. Tamibarotene;
Reaction scheme is:
Wherein, 1 in the reaction scheme the first step is acenaphthene imidazoles N-heterocyclic carbine allyl palladium chloride catalyzer, and structural formula is:
.
2. acenaphthene according to claim 1 imidazoles N-heterocyclic carbine allyl palladium chloride compound for catalysis synthesize the method for Tamibarotene, it is characterized by the carbonyl amination reaction that utilizes the novel acenaphthene of high catalytic activity imidazoles N-heterocyclic carbine allyl palladium chloride catalyst, prepare efficiently the Tamibarotene precursor compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310261167.9A CN103408450B (en) | 2013-06-27 | 2013-06-27 | Method for catalytically synthesizing tamibarotene through acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310261167.9A CN103408450B (en) | 2013-06-27 | 2013-06-27 | Method for catalytically synthesizing tamibarotene through acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103408450A true CN103408450A (en) | 2013-11-27 |
| CN103408450B CN103408450B (en) | 2015-05-13 |
Family
ID=49601509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310261167.9A Expired - Fee Related CN103408450B (en) | 2013-06-27 | 2013-06-27 | Method for catalytically synthesizing tamibarotene through acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103408450B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107188818A (en) * | 2017-07-14 | 2017-09-22 | 安徽世华化工有限公司 | A kind of preparation method of food additives capsaicine |
| CN107442172A (en) * | 2017-03-21 | 2017-12-08 | 复旦大学 | Pyridine bridging N-heterocyclic carbine triphenylphosphine hydrogen chloride ruthenium catalyst and its preparation and catalytic applications |
| CN109794295A (en) * | 2019-02-20 | 2019-05-24 | 中国科学院兰州化学物理研究所 | A kind of acenaphthene imidazole base N-heterocyclic carbine metal palladium complex catalyst and its preparation and application |
-
2013
- 2013-06-27 CN CN201310261167.9A patent/CN103408450B/en not_active Expired - Fee Related
Non-Patent Citations (3)
| Title |
|---|
| GREGORIO GUISADO-BARRIOS ET AL.: "Pyracene-Linked Bis-Imidazolylidene Complexes of Palladium and Some Catalytic Benefits Produced by Bimetallic Catalysts", 《CHEM. EUR. J.》 * |
| KALYAN V. VASUDEVAN ET AL.: "Synthesis and coordination compounds of a bis(imino)acenaphthene (BIAN)-supported N-heterocyclic carbene", 《DALTON TRANSACTIONS》 * |
| 尹静梅等: "钯催化芳香族卤化物羰基化反应的研究进展", 《天然气化工》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107442172A (en) * | 2017-03-21 | 2017-12-08 | 复旦大学 | Pyridine bridging N-heterocyclic carbine triphenylphosphine hydrogen chloride ruthenium catalyst and its preparation and catalytic applications |
| CN107442172B (en) * | 2017-03-21 | 2021-01-26 | 复旦大学 | Pyridine-bridged N-heterocyclic carbene triphenylphosphine ruthenium hydrochloride catalyst, and preparation and catalytic application thereof |
| CN107188818A (en) * | 2017-07-14 | 2017-09-22 | 安徽世华化工有限公司 | A kind of preparation method of food additives capsaicine |
| CN109794295A (en) * | 2019-02-20 | 2019-05-24 | 中国科学院兰州化学物理研究所 | A kind of acenaphthene imidazole base N-heterocyclic carbine metal palladium complex catalyst and its preparation and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103408450B (en) | 2015-05-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Price et al. | Initial synthesis of UK-427,857 (Maraviroc) | |
| CN111925381B (en) | Synthesis method of baroxavir key intermediate | |
| KR20170131508A (en) | METHOD FOR PREPARING LEDIPHASBIR AND ITS DERIVATIVES AND INTERMEDIATE COMPOUND FOR THE PREPARATION OF REDIPASVIR | |
| CN103408450B (en) | Method for catalytically synthesizing tamibarotene through acenaphthene imidazole n-heterocyclic carbine allyl palladium chloride compound | |
| Radchenko et al. | Synthesis of 2-azaspiro [3.3] heptane-derived amino acids: ornitine and GABA analogues | |
| CN103833570B (en) | Synthesis method of oseltamivir | |
| CN103420855A (en) | Trans-4-amino cyclohexylmethanol hydrochloride and preparation method thereof | |
| CN101735134A (en) | Chiral 3-hydroxy pyrrolidone compound and preparation method and application thereof | |
| CN103601645A (en) | Preparation method of 1-(phenethylamino) propane-2-alcoholic compounds or salts thereof | |
| Hajipour et al. | Cobalt-catalyzed CH activation/CO formation: Synthesis of benzofuranones | |
| CN101081851A (en) | Preparation method of alpha-aza toroid drug template | |
| Swift et al. | Tandem aza-Claisen rearrangement and ring-closing metathesis reactions: the stereoselective synthesis of functionalised carbocyclic amides | |
| CN105237602B (en) | A kind of preparation method of 2- amino arabinosy ladenosine | |
| CN102260213B (en) | Method for preparing tolvaptan | |
| CN102993040B (en) | A kind of novel method of synthesizing Agomelatine | |
| CN107417548A (en) | Than his intermediate of department and preparation method thereof | |
| Chen et al. | A facile synthesis of saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine | |
| CN103121976A (en) | Preparation method of N-monosubstituted homopiperazines | |
| CN107963976A (en) | A kind of preparation method of phenyl ethyl amine compounds intermediate | |
| CN105884687A (en) | Preparation method of 5-benzyl benzydamine | |
| Zhao et al. | Visible light-induced manganese-catalyzed aminocarbonylation of alkyl iodides under atmospheric pressure at room temperature | |
| Srivastava et al. | A Practical and Inexpensive Synthesis of the Taxol C-13 Side Chain; N-Benzoyl-(2 R, 3 S)-3-Phenylisoserine | |
| CN103497139B (en) | A kind of method utilizing boron lithium thing to prepare cis-hexahydroisoindoline | |
| CN104292130B (en) | A kind of synthetic method of EBP520 intermediate 2-hydroxyl-3-amino-4-cyclobutyl butanamide hydrochloride | |
| CN117447398A (en) | Synthesis method of cyclopentyl-substituted fatty amide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150513 Termination date: 20200627 |