CN108218784A - A kind of preparation method of Nilutamide - Google Patents
A kind of preparation method of Nilutamide Download PDFInfo
- Publication number
- CN108218784A CN108218784A CN201810038856.6A CN201810038856A CN108218784A CN 108218784 A CN108218784 A CN 108218784A CN 201810038856 A CN201810038856 A CN 201810038856A CN 108218784 A CN108218784 A CN 108218784A
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- CN
- China
- Prior art keywords
- nilutamide
- preparation
- cyano
- reaction
- dimethyl
- 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.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
Abstract
The invention discloses a kind of preparation methods of Nilutamide, using 3 trifluoromethyl, 4 cyano chlorobenzene as raw material, and 5,5 Dimethyl Hydan are in dimethyl sulfoxide solvent, it is reacted under alkalinity and potassium iodide catalytic action, gained crude product is purified by recrystallization.Method provided by the invention has the characteristics that reaction step is short, reaction condition is mild, environmental pollution is smaller.
Description
Technical field
The present invention relates to a kind of preparation methods of Nilutamide, belong to chemosynthesis technical field.
Background technology
Nilutamide chemical formula is the non steroidal antiandrogen object similar with Flutamide, can be combined with androgen receptor
And without androgenic effect, so as to which androgen be blocked to be combined with these receptors, play anti-androgenic effect.For prostate cancer or turn
Shifting property prostate cancer therapy, can merge application with operative treatment and chemotherapy.
Niemi Lu Te is usually made by two kinds of hair methods once：Route one：It is anti-by 3- trifluoromethyl -4- cyano-anilines and phosgene
3- trifluoromethyl -4- cyano-phenyl isocyanates should be obtained, then Niemi Shandong is obtained with the cyclization of 2- amino -2- dicyanopropanes, hydrolysis
It is special.Route two：Be made 3- trifluoromethyl -4- cyano iodobenzenes through diazotising by 3- trifluoromethyl -4- cyano-anilines, then with 5,5- bis-
Niemi Lu Te is made in methyl hydantoin reaction.
Route one in reacting needs that 3- trifluoromethyl -4- cyano-phenyl isocyanates is made with violent in toxicity solid phosgene；It is former
Material 2- amino -2- dicyanopropanes are not easy to buy, and preparation is needed with violent in toxicity cyanide；Hydrochloric acid heating is needed in hydrolytic process,
Equipment is corroded larger.
Diazotising can generate a large amount of acid waste water during route two reacts, and be unfavorable for environmental protection.Second step is in 10 times of volumes
Back flow reaction in n,N-Dimethylformamide, reaction temperature is high, and post processing wastewater flow rate is big.
Invention content
The technical problem to be solved by the invention is to provide a kind of reaction step is short, reaction condition is mild, environmental pollution
Smaller Nilutamide preparation method.
In order to solve the above technical problems, the technical solution adopted by the present invention is：
A kind of preparation method of Nilutamide, using 3- trifluoromethyl -4- cyano chlorobenzenes as raw material, with 5,5- Dimethyl Hydan
It in dimethyl sulfoxide solvent, is reacted under alkalinity and potassium iodide catalytic action, gained crude product is carried out by recrystallizing
Purifying.
Wherein described dimethyl sulfoxide (DMSO) dosage is the 3- trifluoromethyls -4- cyano chlorobenzene and 5,5- dimethyl sea
Because of 1-2 times of volume mass ratio of total amount.
Reaction temperature is 50-150 DEG C, and the reaction time is 6 hours.
The reaction temperature is 80 DEG C.
Alkalinity is provided using potassium hydroxide.
Recrystallization solvent is ethyl alcohol.
Recrystallization solvent is toluene.
The advantageous effect that the present invention is reached：Synthetic route of the present invention is simple, only single step reaction；Reaction raw materials are cheaply easy
, it is at low cost；Without using severe poisonous chemicals in reaction process, reaction condition is mild, does not need to pyroreaction, system quantity of solvent
It is few, greatly reduce the generation of waste water.
Specific embodiment
The invention will be further described below.Following embodiment is only used for the technical side for clearly illustrating the present invention
Case, and be not intended to limit the protection scope of the present invention and limit the scope of the invention.
Embodiment 1
100mL dimethyl sulfoxide (DMSO)s are added in into 250ml there-necked flasks, it is disposable to put into 30g 5,5- Dimethyl Hydan, then add
Enter 50g 3- trifluoromethyl -4- cyano chlorobenzenes, then add the potassium iodide of 0.5g, the potassium hydroxide of 20g is then heated to 80
DEG C reaction 6 hours, after the reaction was complete, be cooled to room temperature, reaction solution be poured into water, filter to obtain yellow solid 58g.Crude product second
Alcohol recrystallizes to obtain Nilutamide sterling 48g, yield 66.3%.
Embodiment 2
10L dimethyl sulfoxide (DMSO)s are added in 30L reaction kettles, disposable to put into 3Kg 5,5- Dimethyl Hydan adds 5Kg
3- trifluoromethyl -4- cyano chlorobenzenes, then add the potassium iodide of 50g, and the potassium hydroxide of 2Kg is then heated to 80 DEG C of reactions 6
Hour, it after the reaction was complete, is cooled to room temperature, reaction solution is poured into water, filter to obtain yellow solid 5.5Kg.Crude product toluene weight
Crystallize to obtain Nilutamide sterling 4.7kg, yield 65%.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the technical principles of the invention, several improvement and deformation can also be made, these are improved and deformation
Also it should be regarded as protection scope of the present invention.
Claims (7)
1. a kind of preparation method of Nilutamide, which is characterized in that using 3- trifluoromethyl -4- cyano chlorobenzenes as raw material, with 5,5-
Dimethyl Hydan is reacted, gained crude product passes through in dimethyl sulfoxide solvent under alkalinity and potassium iodide catalytic action
Recrystallization is purified.
A kind of 2. preparation method of Nilutamide as described in claim 1, which is characterized in that wherein described dimethyl sulfoxide (DMSO) agent
Measure the 1-2 times of volume mass ratio for the 3- trifluoromethyls -4- cyano chlorobenzene and 5, the 5- Dimethyl Hydan total amount.
3. a kind of preparation method of Nilutamide as claimed in claim 2, which is characterized in that reaction temperature is 50-150 DEG C,
Reaction time is 6 hours.
4. a kind of preparation method of Nilutamide as claimed in claim 3, which is characterized in that the reaction temperature is 80 DEG C.
5. a kind of preparation method of Nilutamide as described in claim 1, which is characterized in that provide alkali using potassium hydroxide
Property.
6. such as a kind of preparation method of Nilutamide of claim 1-5 any one of them, which is characterized in that recrystallization solvent is
Ethyl alcohol.
7. such as a kind of preparation method of Nilutamide of claim 1-5 any one of them, which is characterized in that recrystallization solvent is
Toluene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810038856.6A CN108218784A (en) | 2018-01-16 | 2018-01-16 | A kind of preparation method of Nilutamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810038856.6A CN108218784A (en) | 2018-01-16 | 2018-01-16 | A kind of preparation method of Nilutamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108218784A true CN108218784A (en) | 2018-06-29 |
Family
ID=62641233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810038856.6A Pending CN108218784A (en) | 2018-01-16 | 2018-01-16 | A kind of preparation method of Nilutamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108218784A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1207732A (en) * | 1995-11-16 | 1999-02-10 | 赫斯特·马里恩·鲁索公司 | Process for preparation of phenylimidazolidine derivs. |
-
2018
- 2018-01-16 CN CN201810038856.6A patent/CN108218784A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1207732A (en) * | 1995-11-16 | 1999-02-10 | 赫斯特·马里恩·鲁索公司 | Process for preparation of phenylimidazolidine derivs. |
Non-Patent Citations (4)
| Title |
|---|
| 唐除痴: "《不对称反应概论》", 31 October 2017 * |
| 张保集: "Cux+催化的N-芳基化反应研究进展", 《化学与生物工程》 * |
| 李倩: "尼鲁米特类化合物的合成", 《中国医药工业杂志》 * |
| 陶晓红: "间三氟甲基苯胺合成尼鲁米特", 《化工生产与技术》 * |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180629 |
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| RJ01 | Rejection of invention patent application after publication |