CN106279063B - A kind of synthetic method of medicine intermediate phenothiazine compound - Google Patents
A kind of synthetic method of medicine intermediate phenothiazine compound Download PDFInfo
- Publication number
- CN106279063B CN106279063B CN201610656463.2A CN201610656463A CN106279063B CN 106279063 B CN106279063 B CN 106279063B CN 201610656463 A CN201610656463 A CN 201610656463A CN 106279063 B CN106279063 B CN 106279063B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- synthetic method
- alkali
- catalyst
- 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.)
- Active
Links
- 0 *c(cccc1)c1[N+][N+] Chemical compound *c(cccc1)c1[N+][N+] 0.000 description 1
- ZNOPJZQTFMGRCB-UHFFFAOYSA-N SSC1=CC=CCC1 Chemical compound SSC1=CC=CCC1 ZNOPJZQTFMGRCB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/20—[b, e]-condensed with two six-membered rings with hydrogen atoms directly attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
Abstract
The present invention relates to a kind of synthetic method can be used as phenothiazine compound shown in the lower formula (III) of medicine intermediate,The method includes：At room temperature, lower formula (I) compound, formula (II) compound, catalyst, ligand, alkali and auxiliary agent are added into organic solvent, is warming up to 70 90 DEG C and is stirred to react 7 10 hours, it is post-treated after completion of the reaction, to obtain the formula (III) compoundWherein, R1、R2It is each independently selected from H, C1‑C6Alkyl, C1‑C6Alkoxy or halogen；X is halogen.The method is promoted by the comprehensive selection of the use of suitable reactants and catalyst, ligand, alkali, auxiliary agent and organic solvent with cooperateing with, and purpose product is obtained so as to high yield, is had a good application prospect and industrial production potential.
Description
Technical field
The present invention relates to a kind of synthetic method containing heteroatomic thick cyclics, relate more particularly in a kind of medicine
The synthetic method of mesosome phenothiazine compound belongs to medicine intermediate synthesis and organic chemical synthesis technical field.
Background technology
Phenothiazine structure occupies highly important status in fields such as organic chemistry, life science, material science.According to report
Road has more than 5,000 phenthazine row compounds, and largely illustrates good bioactivity at present, such as can be used as anti-
Chlorpromazine, antineoplastic, and for antiemetic, antipruritic etc..
Just because of the such important purposes and application prospect of phenothiazine compound, the research of synthetic method by
The most attention of people.
So far, in the prior art it has been reported that a variety of synthetic methods in relation to phenothiazine compound, as example
It lifts as follows：
(" the Assembly of Substituted Phenothiazines by a Seq uentially such as Ma Dawei
Controlled CuI/l-Proline-Catalyzed Cascade C-S and C-N B ond Formation”,
Angew.Chem.Int.Ed., 2010,49,1291-1294) report a kind of continuous C-S keys of CuI/L- Proline-Catalyzeds,
C-N keys construct reaction, and phenothiazine compound is successfully prepared, and reaction equation is as follows：
(" the Synthesis of phenothiazines via ligand-free CuI- such as Zeng Qingle
catalyzed cascade C-S and C-N coupling of aryl ortho-dihalides and ortho-
Aminobenzenethiols ", Chem.Commun., 2012,48,5367-5367) report a kind of preparation of CuI/ base catalysis
The method of phenothiazine compound, reaction equation are as follows：
As described above, a variety of methods of synthesis phenothiazine compound are disclosed in the prior art, but these methods are still deposited
In certain defect, such as products collection efficiency is relatively low, reaction process is complicated etc., therefore for the synthesis side of phenothiazine compound
Method, there are still the necessity for continuing research.
The present invention provides a kind of synthetic method of phenothiazine compound, this method uses specific reactant and synthesis
Reaction system obtains purpose product so as to high yield, and completely new method is provided for the synthesis of phenothiazine compound, tool
There are good application prospect and industrial production potential.
Invention content
In order to overcome defect as indicated above and seek the novel method for synthesizing of phenothiazine compound, the present inventor
It conducts in-depth research and explores, after having paid enough creative works, so as to complete the present invention.
Specifically, technical scheme of the present invention and content are related to a kind of lower formula (III) institute can be used as medicine intermediate
Show the synthetic method of phenothiazine compound,
The method includes：At room temperature, lower formula (I) compound, formula (II) compound, catalysis are added into organic solvent
Agent, ligand, alkali and auxiliary agent are warming up to 70-90 DEG C and are stirred to react 7-10 hours, post-treated after completion of the reaction, to obtain
Formula (III) compound,
Wherein, R1、R2It is each independently selected from H, C1-C6Alkyl, C1-C6Alkoxy or halogen；
X is halogen.
In the synthetic method of the present invention, the C1-C6The meaning of alkyl refers to the straight chain for having 1-6 carbon atom
Or branched alkyl, it may be, for example, methyl, ethyl, n-propyl, isopropyl, normal-butyl, sec-butyl, isobutyl group, uncle in non-limiting manner
Butyl, n-pentyl, isopentyl or n-hexyl etc..
In the synthetic method of the present invention, the C1-C6The meaning of alkoxy refers to the C for having above-mentioned implication1-C6
The group that alkyl obtains after being connected with oxygen atom.
In the synthetic method of the present invention, the halogen is halogen, may be, for example, F, Cl, Br or I.
In the synthetic method of the present invention, the catalyst is molar ratio 1:Four carbonyl of organoiron compound of 3-4
The mixture of nickel.
Wherein, the organoiron compound is bis- (diphenylphosphine) ferrocene of 1,1'-, 1,1'- bis- (diisopropyl phosphines) two
Luxuriant iron or 1, any one in 1'- dibromof errocenes, bis- (diisopropyl phosphine) ferrocene of most preferably 1,1'-.
In the synthetic method of the present invention, the ligand is the L1 or L2 of following formula,
The ligand is most preferably L1.
In the synthetic method of the present invention, the alkali is NaOH, sodium ethoxide, diethanol amine, 1,8- diazabicylos
11 carbon -7- alkene (DBU), lithium diisopropylamine (LDA), 1,4- diazabicylos [2.2.2] octane (DABCO) or trimethylamine
In any one, most preferably Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane (DABCO).
In the synthetic method of the present invention, the auxiliary agent is 1,2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates.
In the synthetic method of the present invention, the organic solvent is volume ratio 2:1 N,N-dimethylformamide
(DMF) with the mixture of chlorobenzene.
Wherein, the dosage of the organic solvent there is no stringent restrictions, those skilled in the art can be according to actual conditions
It carries out suitably selection and determines, such as its dosage size is no longer carried out detailed herein with facilitating reaction progress and post-processing
Thin description.
In the synthetic method of the present invention, the molar ratio of formula (I) compound and formula (II) compound is 1:
1.4-2 may be, for example, 1:1.4、1:1.6、1:1.8 or 1:2.
In the synthetic method of the present invention, formula (I) compound is with catalyst (with the total mole number of two kinds of components
Meter) molar ratio be 1:0.1-0.2 may be, for example, 1:0.1、1:0.15 or 1:0.2.
In the synthetic method of the present invention, the molar ratio of formula (I) compound and ligand is 1:0.08-0.14,
It may be, for example,:0.08、1:0.1、1:0.12 or 1:0.14.
In the synthetic method of the present invention, the molar ratio of formula (I) compound and alkali is 1:1-1.6 such as can
It is 1:1、1:1.3 or 1:1.6.
In the synthetic method of the present invention, the molar ratio of formula (I) compound and auxiliary agent is 1:0.1-0.2, example
Such as can be 1:0.1、1:0.15 or 1:0.2.
In the synthetic method of the present invention, post-processing after reaction is specific as follows：After reaction, to reaction
Deionized water is added in mixture fully to vibrate, then ethyl acetate extracts 2-3 times, merges organic phase, then use saturated salt solution
Washing 2-3 times, separates organic phase and merges, and anhydrous magnesium sulfate drying is concentrated under reduced pressure, residue crosses silica gel post separation, with volume
Than 1:2 chloroform and the mixture of petroleum ether are eluted, to obtain the formula (III) compound.
In conclusion the present invention provides a kind of synthetic method of phenothiazine compound, the method passes through suitable anti-
Answer object use and catalyst, ligand, alkali, auxiliary agent and organic solvent comprehensive selection promote with cooperateing with, so as to high yield
Rate obtains purpose product, has a good application prospect and industrial production potential.
Specific implementation mode
Below by specific embodiment, the present invention is described in detail, but the purposes of these exemplary embodiments and
Purpose is only used for enumerating the present invention, not constitutes any type of any restriction to the real protection scope of the present invention, more non-to incite somebody to action
Protection scope of the present invention is confined to this.
Embodiment 1
At room temperature, to appropriate organic solvent (for volume ratio 2:The mixing of 1 N,N-dimethylformamide (DMF) and chlorobenzene
Object) in be added formula (I) compound on 100mmol, the upper formula (II) compounds of 140mmol, 20mmol catalyst (for 5mmol 1,
The mixture of 1'- bis- (diisopropyl phosphine) ferrocene and 15mmol nickel carbonyls), 8mmol ligand Ls 1,160mmol alkali DABCO and
10mmol auxiliary agents 1,2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates then heat to 70 DEG C and stir at such a temperature anti-
It answers 10 hours；
After reaction, deionized water is added into reaction mixture fully to vibrate, then ethyl acetate extracts 2-3 times,
Merging organic phase, then with saturated common salt water washing 2-3 time, separates organic phase and merge, anhydrous magnesium sulfate is dried, reduced pressure,
Residue crosses silica gel post separation, with volume ratio 1:2 chloroform and the mixture of petroleum ether are eluted, to obtain above formula
(III) compound, yield 95.8%.
1H NMR(d6-DMSO,400 MHz):δ 8.59 (brs, 1H), 6.93 (d, J=8.2Hz, 1H), 6.76 (dd, J=
8.2,2.2 Hz, 1H), 6.68 (d, J=2.2 Hz, 1H), 6.64-6.61 (m, 2H), 6.60-6.58 (m, 1H), 3.66 (s,
3H)。
Embodiment 2
At room temperature, to appropriate organic solvent (for volume ratio 2:1 N,N-dimethylformamide
(DMF) with the mixture of chlorobenzene) in be added 100mmol on formula (I) compound, the upper formula (II) compounds of 200mmol,
10mmol catalyst (for the mixture of 2mmol 1,1'- bis- (diisopropyl phosphine) ferrocene and 8mmol nickel carbonyls), 14mmol
Ligand L 1,100mmol alkali DABCO and 20mmol auxiliary agent 1,2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates, then heat to
It 90 DEG C and is stirred to react at such a temperature 7 hours；
After reaction, deionized water is added into reaction mixture fully to vibrate, then ethyl acetate extracts 2-3 times,
Merging organic phase, then with saturated common salt water washing 2-3 time, separates organic phase and merge, anhydrous magnesium sulfate is dried, reduced pressure,
Residue crosses silica gel post separation, with volume ratio 1:2 chloroform and the mixture of petroleum ether are eluted, to obtain above formula
(III) compound, yield 95.2%.
1H NMR(d6-DMSO,400MHz):δ8.24(s,1H),6.81-6.72(m,2H),6.67-6.55(m,4H),
3.68(s,3H),2.15(s,3H)。
Embodiment 3
At room temperature, to appropriate organic solvent (for volume ratio 2:The mixing of 1 N,N-dimethylformamide (DMF) and chlorobenzene
Object) in be added formula (I) compound on 100mmol, the upper formula (II) compounds of 170mmol, 15mmol catalyst (for 3.3mmol 1,
The mixture of 1'- bis- (diisopropyl phosphine) ferrocene and 11.7mmol nickel carbonyls), 11mmol ligand Ls 1,130mmol alkali
DABCO and 15mmol auxiliary agents 1,2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates then heat to 80 DEG C and at such a temperature
It is stirred to react 8 hours；
After reaction, deionized water is added into reaction mixture fully to vibrate, then ethyl acetate extracts 2-3 times,
Merging organic phase, then with saturated common salt water washing 2-3 time, separates organic phase and merge, anhydrous magnesium sulfate is dried, reduced pressure,
Residue crosses silica gel post separation, with volume ratio 1:2 chloroform and the mixture of petroleum ether are eluted, to obtain above formula
(III) compound, yield 95.4%.
1H NMR(d6-DMSO,400MHz):δ 8.34 (s, 1H), 6.80-6.71 (m, 4H), 6.57 (d, J=8.0Hz,
2H),2.10(s,6H)。
Embodiment 4
At room temperature, to appropriate organic solvent (for volume ratio 2:The mixing of 1 N,N-dimethylformamide (DMF) and chlorobenzene
Object) in be added formula (I) compound on 100mmol, the upper formula (II) compounds of 190mmol, 13.5mmol catalyst (for 3mmol 1,
The mixture of 1'- bis- (diisopropyl phosphine) ferrocene and 10.5mmol nickel carbonyls), 13mmol ligand Ls 1,150mmol alkali
DABCO and 12mmol auxiliary agents 1,2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates then heat to 85 DEG C and at such a temperature
It is stirred to react 9 hours；
After reaction, deionized water is added into reaction mixture fully to vibrate, then ethyl acetate extracts 2-3 times,
Merging organic phase, then with saturated common salt water washing 2-3 time, separates organic phase and merge, anhydrous magnesium sulfate is dried, reduced pressure,
Residue crosses silica gel post separation, with volume ratio 1:2 chloroform and the mixture of petroleum ether are eluted, to obtain above formula
(III) compound, yield 95.6%.
1H NMR(d6-DMSO,400MHz):δ8.95(s,1H),6.95-6.88(m,2H),6.84-6.77(m,2H),
6.67(s,2H)。
Embodiment 5-20
Embodiment 5-8：Except bis- (diisopropyl phosphine) ferrocene of the 1,1'- in catalyst are replaced with the bis- (diphenyl of 1,1'-
Phosphine) outside ferrocene, other operations are constant, to repeat to implement embodiment 1-4, sequentially obtain embodiment 5-8.
Embodiment 9-12：It is luxuriant except bis- (diisopropyl phosphine) ferrocene of the 1,1'- in catalyst are replaced with 1,1'- dibromos two
Outside iron, other operations are constant, to repeat to implement embodiment 1-4, sequentially obtain embodiment 9-12.
Embodiment 13-16：Except catalyst is replaced with the one-component 1 that dosage is the sum of total dosage of original two kinds of components,
Outside bis- (diisopropyl phosphine) ferrocene of 1'-, other operations are constant, to repeat to implement embodiment 1-4, sequentially implemented
Example 13-16.
Embodiment 17-20：Except catalyst is replaced with the one-component four that dosage is the sum of total dosage of original two kinds of components
Outside carbonyl nickel, other operations are constant, to repeat to implement embodiment 1-4, sequentially obtain embodiment 17-20.
As a result it see the table below 1.
Table 1
It can be seen that only using the mixture of bis- (diisopropyl phosphine) ferrocene of 1,1'- and nickel carbonyl as catalysis
When agent, the superior product yield of embodiment 1-4 could be obtained.And when using any one-component, cause yield to have significantly
Reduction when nickel carbonyl (especially only be used only).It can also be seen that in all organoiron compounds, 1,1'- bis- (two
Isopropyl phosphine) effect of ferrocene is better than other organoiron compounds.
Embodiment 21-28
Embodiment 21-24：In addition to organic ligand L1 is replaced with L2, other operations are constant, to repeat to implement reality
A 1-4 is applied, embodiment 21-24 is sequentially obtained.
Embodiment 25-28：In addition to omitting organic ligand L1, other operations are constant, to repeat to implement embodiment
1-4 sequentially obtains embodiment 25-28.
As a result 2 be see the table below.
Table 2
It can be seen that although ligand L 1 and L2 structures are relatively, its effect will be significantly better than L2, this proves ligand knot
The minor alteration of structure all can cause effect to produce uncertain change.It can also be seen that when without using L1 or L2, yield
It is reduced to 82% or so, is reduced more notable.
Embodiment 29-52
Embodiment 29-32：In addition to alkali DABCO is replaced with NaOH, other operations are constant, to repeat to implement implementation
Example 1-4, sequentially obtains embodiment 29-32.
Embodiment 33-36：In addition to alkali DABCO is replaced with sodium ethoxide, other operations are constant, to repeat to implement reality
A 1-4 is applied, embodiment 33-36 is sequentially obtained.
Embodiment 37-40：In addition to alkali DABCO is replaced with diethanol amine, other operations are constant, to repeat to implement
Embodiment 1-4 sequentially obtains embodiment 37-40.
Embodiment 41-44：Except alkali DABCO is replaced with 1,8- diazabicylos, 11 carbon -7- alkene (DBU) outside, Qi Tacao
Work is constant, to repeat to implement embodiment 1-4, sequentially obtains embodiment 41-44.
Embodiment 45-48：Except in addition to alkali DABCO is replaced with lithium diisopropylamine (LDA), other operations are constant,
To repeat to implement embodiment 1-4, embodiment 45-48 is sequentially obtained.
Embodiment 49-52：In addition to alkali DABCO is replaced with trimethylamine, other operations are constant, to repeat to implement reality
A 1-4 is applied, embodiment 49-52 is sequentially obtained.
As a result 3 be see the table below.
Table 3
It can be seen that for alkali, DABCO have the effect of it is best, and trimethylamine, DBU and NaOH relative efficacies compared with
Difference.
Embodiment 53-56
Except auxiliary agent 1 is dispensed, outside 2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates, other operations are constant, to weight
Embodiment 1-4 is implemented again, sequentially obtains embodiment 53-56.
It was found that the products collection efficiency of embodiment 53-56 is 86.5-87.7%, about 7-9 hundred is reduced relative to embodiment 1-4
Branch, this proves that auxiliary agent 1, the use of 2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates can significantly improve final production
Produce rate, achieving unexpected technology improves.
Embodiment 57-64
Embodiment 57-60：In addition to organic solvent is replaced with one-component DMF, other operations are constant, real to repeat
Embodiment 1-4 has been applied, embodiment 57-60 is sequentially obtained.
Embodiment 61-64：In addition to organic solvent is replaced with one-component chlorobenzene, other operations are constant, to repeat
Embodiment 1-4 is implemented, embodiment 61-64 is sequentially obtained.
As a result 4 be see the table below.
Table 4
It can be seen that when using single solvent group timesharing, products collection efficiency will be significantly lower than the mixture using DMF+ chlorobenzenes
When effect, this proof can further improve reaction effect when using double solvents.
In conclusion the present invention provides a kind of synthetic method of phenothiazine compound, the method passes through suitable anti-
Answer object use and catalyst, ligand, alkali, auxiliary agent and organic solvent comprehensive selection promote with cooperateing with, so as to high yield
Rate obtains purpose product, has a good application prospect and industrial production potential.
It should be appreciated that the purposes of these embodiments is merely to illustrate the present invention and is not intended to limitation protection model of the invention
It encloses.In addition, it should also be understood that, after reading the technical contents of the present invention, those skilled in the art can make the present invention each
Kind change, modification and/or variation, all these equivalent forms equally fall within and are protected defined by the application the appended claims
Within the scope of shield.
Claims (6)
1. the synthetic method of phenothiazine compound shown in a kind of lower formula (III),
The method includes：At room temperature, lower formula (I) compound is added into organic solvent, formula (II) compound, catalyst, matches
Body, alkali and auxiliary agent are warming up to 70-90 DEG C and are stirred to react 7-10 hours, post-treated after completion of the reaction, to obtain the formula
(III) compound,
Wherein, R1、R2It is each independently selected from H, C1-C6Alkyl, C1-C6Alkoxy or halogen；
X is halogen；
The catalyst is molar ratio 1:The organoiron compound of 3-4 and the mixture of nickel carbonyl；Wherein, the Organic Iron
Conjunction object is bis- (diisopropyl phosphine) ferrocene of 1,1'-；
The ligand is the L1 of following formula,
The alkali is 1,4- diazabicylos [2.2.2] octane；
The auxiliary agent is 1,2- dimethyl -3- hydroxyethyl imidazole hexafluorophosphates；
The organic solvent is volume ratio 2:1 N,N-dimethylformamide and the mixture of chlorobenzene.
2. synthetic method as described in claim 1, it is characterised in that：Formula (I) compound is rubbed with formula (II) compound
You are than being 1:1.4-2.
3. synthetic method as described in claim 1, it is characterised in that：Formula (I) compound and the molar ratio of catalyst are
1:0.1-0.2。
4. synthetic method as described in claim 1, it is characterised in that：Formula (I) compound and the molar ratio of ligand are 1:
0.08-0.14。
5. synthetic method as described in claim 1, it is characterised in that：Formula (I) compound and the molar ratio of alkali are 1:1-
1.6。
6. synthetic method as described in any one in claim 1-5, it is characterised in that：Formula (I) compound and auxiliary agent rub
You are than being 1:0.1-0.2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610656463.2A CN106279063B (en) | 2016-08-11 | 2016-08-11 | A kind of synthetic method of medicine intermediate phenothiazine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610656463.2A CN106279063B (en) | 2016-08-11 | 2016-08-11 | A kind of synthetic method of medicine intermediate phenothiazine compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106279063A CN106279063A (en) | 2017-01-04 |
| CN106279063B true CN106279063B (en) | 2018-07-27 |
Family
ID=57669387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610656463.2A Active CN106279063B (en) | 2016-08-11 | 2016-08-11 | A kind of synthetic method of medicine intermediate phenothiazine compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106279063B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3669979A (en) * | 1967-12-14 | 1972-06-13 | Gaf Corp | Novel process for the production of 2-benzothiazolyl-phenol and derivatives thereof employing phosphorus trichloride as a catalyst |
| CN104311508A (en) * | 2014-09-29 | 2015-01-28 | 苏州大学 | Synthetic method of iron-catalyzed phenothiazine compound |
| CN105669590A (en) * | 2016-03-08 | 2016-06-15 | 四川墨凯科技有限公司 | Catalyst-free technique for synthesizing phenothiazine drug intermediate |
-
2016
- 2016-08-11 CN CN201610656463.2A patent/CN106279063B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3669979A (en) * | 1967-12-14 | 1972-06-13 | Gaf Corp | Novel process for the production of 2-benzothiazolyl-phenol and derivatives thereof employing phosphorus trichloride as a catalyst |
| CN104311508A (en) * | 2014-09-29 | 2015-01-28 | 苏州大学 | Synthetic method of iron-catalyzed phenothiazine compound |
| CN105669590A (en) * | 2016-03-08 | 2016-06-15 | 四川墨凯科技有限公司 | Catalyst-free technique for synthesizing phenothiazine drug intermediate |
Non-Patent Citations (1)
| Title |
|---|
| Weiye Hu 等.Method for the Synthesis of Phenothiazines via a Domino Iron Catalyzed C−S/C−N Cross-Coupling Reaction.《J. Org. Chem.》.2015,第80卷6128-6132. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106279063A (en) | 2017-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107445795A (en) | A kind of synthetic method of the aryl building block of the fluoro ethyl of 2 bromine 1,1,2,2 four substitution | |
| CN105175373B (en) | Synthetic method of aryl ketone coumarin derivative | |
| CN106279063B (en) | A kind of synthetic method of medicine intermediate phenothiazine compound | |
| CN107324964B (en) | Synthetic method of biphenyl derivative | |
| CN105085320B (en) | Synthesis method of dicyano substituted biphenyl compounds | |
| CN105330690B (en) | A kind of synthetic method of pharmaceutical intermediate aryl ketones phosphonate compound | |
| CN105732297B (en) | A kind of synthetic method of organic intermediate acetylene compound | |
| CN105061286B (en) | A kind of synthetic method of alkynyl substituted azoles | |
| CN107915653A (en) | Catalysis ester and amine carry out the method that reaction prepares acid amides | |
| CN106432001A (en) | Synthesis method of dienyl sulfone compounds | |
| CN105198791A (en) | Synthetic method of medicine intermediate aza spiro compound | |
| CN104672180A (en) | Chiral preparation method of [(1S)-3-methyl-1-[[(2R)-2-methylepoxyethyl]carbonyl]butyl]tert-butyl carbamate | |
| CN100478061C (en) | High temperature resistant surfactant and synthesis method thereof | |
| CN105001133B (en) | Synthetic method for medical intermediate diaryl sulfide compound | |
| CN104610002B (en) | A kind of method of aryl hydrazine synthesis symmetry biphenyl | |
| CN105218395B (en) | A kind of synthetic method of azo-compound | |
| CN105153152B (en) | A kind of synthetic method of imidazoles fused ring compound | |
| CN106146364B (en) | A kind of synthetic method of sulfenamide compound | |
| WO2008059960A1 (en) | Method for producing quarter-pyridine derivative and intermediate of quarter-pyridine derivative | |
| CN105330566A (en) | Synthetic method of dicyano compound | |
| CN104529879B (en) | A kind of synthetic method of 2-substituted-pyridines pharmaceutical intermediate compound | |
| CN106045887B (en) | A kind of synthetic method of N- ethyls sulfenamide compound | |
| CN105384677B (en) | A kind of synthetic method of medicine intermediate aryl substituted indole class compound | |
| CN105732456A (en) | Synthetic method for asymmetric substituted pyrrole compound | |
| CN105503767B (en) | The synthetic method of body oxazole ketone compounds between in a kind of doctor's medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20180607 Address after: 210000 Qian De road, Jiangning District, Nanjing, Jiangsu Province, No. 5 Applicant after: Nanjing Popper biomedicine R & D Co., Ltd. Address before: 102107 No. 28, South Tianmen village, Pearl Spring Township, Yanqing, Beijing Applicant before: Yu Jinlong |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |