CN106083670A - The synthetic method of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene - Google Patents
The synthetic method of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene Download PDFInfo
- Publication number
- CN106083670A CN106083670A CN201610403800.7A CN201610403800A CN106083670A CN 106083670 A CN106083670 A CN 106083670A CN 201610403800 A CN201610403800 A CN 201610403800A CN 106083670 A CN106083670 A CN 106083670A
- Authority
- CN
- China
- Prior art keywords
- ether
- iprotiazem
- benzene
- synthetic method
- amino
- 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
- DQQQRZDYNGUJSP-BGRWSDHPSA-N C/C(/CC[N+]([O-])=O)=C/C=C\CF Chemical compound C/C(/CC[N+]([O-])=O)=C/C=C\CF DQQQRZDYNGUJSP-BGRWSDHPSA-N 0.000 description 1
- 0 CC(*)Sc1ccccc1[N+]([O-])=O Chemical compound CC(*)Sc1ccccc1[N+]([O-])=O 0.000 description 1
- YWKQZMMKIRSOCZ-VMPITWQZSA-N CC(C)C/C=C(\CN)/S(C)(O)=O Chemical compound CC(C)C/C=C(\CN)/S(C)(O)=O YWKQZMMKIRSOCZ-VMPITWQZSA-N 0.000 description 1
- SOKYEGOHVZMJQG-UHFFFAOYSA-N CCC=C(C(C)S(C(C)C)O)N Chemical compound CCC=C(C(C)S(C(C)C)O)N SOKYEGOHVZMJQG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to technical field of medicine synthesis, the synthetic method of particularly a kind of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene, initially with o-fluoronitrobenzene, sodium hydride, isopropyl mercaptan synthesis 2 (iprotiazem ether) Nitrobenzol crude product, then by direct for crude product iron powder reducing, become salt, obtain 2 (iprotiazem ether) anilinechloride, finally by 2 (iprotiazem ether) anilinechloride in water by dropping hydrogen peroxide oxidation, become salt, dissociate and obtain target product, this synthetic method is relatively simple, sewage quantity is less, energy consumption is relatively low, production cost is relatively low, the purity preparing product is higher, yield is higher, it is prone to industrialized production, suitable further genralrlization application.
Description
Technical field
The invention belongs to technical field of medicine synthesis, particularly a kind of cancer therapy drug Ceritinib intermediate 1-amino-2-
The synthetic method of (isopropyl sulphonyl) benzene.
Background technology
1-amino-2-(isopropyl sulphonyl) benzene, CAS.76697-50-2, is in the middle of a kind of cancer therapy drug Ceritinib key
Body, its structural formula is:Novartis (Novartis) announces on April 29th, 2014, anticarcinogen Zykadia
(ceritinib) obtaining FDA approval, after treating through Xalkori (crizotinib), sb.'s illness took a turn for the worse or does not tolerates Xalkori
The treatment of positive (ALK+) Metastatic Nsclc (NSCLC) patient of anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase.Before this, FDA awards
Giving Zykadia breakthrough therapy identification, Zykadia is a kind of oral, selectivity anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase (ALK) inhibitor.
In the clinical treatment of pulmonary carcinoma, ALK is an important therapeutic targets.ALK gene can express one with other gene fusion
Abnormal fusion protein, promotes formation and the growth of cancerous cell.FDA authorizes the breakthrough therapy of Zykadia in March, 2013 and recognizes
Fixed.
According to existing route, by intermediate 1-(isopropelsulfonyl)-2-Nitrobenzol, then obtain target product through reduction
Thing 1-amino-2-(isopropyl sulphonyl) benzene, the synthesis of 1-(isopropelsulfonyl)-2-Nitrobenzol, this author is at CN
Its synthetic method described in 104592068A, and the synthesis of this compound needs in DMF, acetic acid 100 DEG C
High-temperature oxydation, has reacted post processing and to have added a large amount of water and be conducive to post processing to be layered, and extracts with dichloromethane, then uses bicarbonate
Sodium, water wash, and energy consumption is too high, and sewage quantity is the biggest.For the problems referred to above, develop in the middle of a kind of novel cancer therapy drug Ceritinib
The synthetic method of body 1-amino-2-(isopropyl sulphonyl) benzene is that those skilled in the art to solve the technical problem that.
Summary of the invention
The technical problem to be solved in the present invention is: in view of prior art energy consumption is higher, operate the problems such as relatively complicated,
Thering is provided one by iron powder reducing, become salt, low-temperature oxidation, become salt again, free obtain sterling, oxidizing temperature is low, and energy consumption is low, production capacity
The synthetic method of higher 1-amino-2-(isopropyl sulphonyl) benzene.
The technical solution adopted for the present invention to solve the technical problems is: a kind of cancer therapy drug Ceritinib intermediate 1-ammonia
The synthetic method of base-2-(isopropyl sulphonyl) benzene, the method has following steps: in aprotic polar solvent, with sodium hydride
Making alkali, isopropyl mercaptan and o-fluoronitrobenzene A react generation 2-(iprotiazem ether) Nitrobenzol B；Again water back warp cross iron powder reducing,
Salt is become to obtain 2-(iprotiazem ether) anilinechloride C；By hydrogen peroxide oxidation, become salt, free obtain target product 1-amino-
2-(isopropyl sulphonyl) benzene D, above-mentioned synthetic method is as follows:
Above-mentioned synthetic method specifically includes following steps:
1) in aprotic polar solvent, o-fluoronitrobenzene and sodium hydride, temperature control-1～1 DEG C of dropping isopropyl mercaptan are added,
After completion of dropwise addition in 0～25 DEG C of reaction to o-fluoronitrobenzene reaction completely, post processing enters water extraction, is concentrated to give crude product 2-(different
Rosickyite ether) Nitrobenzol；
Wherein, aprotic polar solvent is 3.0～8.0 with the mass ratio of o-fluoronitrobenzene, sodium hydride and o-fluoronitrobenzene
Mol ratio be 1.1～2.0, the mol ratio of isopropyl mercaptan and o-fluoronitrobenzene is 1.2～1.5；
2) step (1) gained 2-(iprotiazem ether) Nitrobenzol is reduced with iron powder, hydrochloric acid in water, terminate rear solvent extraction
Take, become salt to obtain 2-(iprotiazem ether) anilinechloride；
Wherein, iron powder is 0.5～3.2 with the mol ratio of 2-(iprotiazem ether) Nitrobenzol, and reaction temperature is 80～100
DEG C, the mol ratio of hydrochloric acid and 2-(iprotiazem ether) Nitrobenzol is 0.32～0.96, salt-forming reagent be 30% acidic alcohol or
30% hydrochloric acid methanol, salt-forming reagent is 1.0～1.5 with the mol ratio of 2-(iprotiazem ether) Nitrobenzol；
3) by step (2) gained 2-(iprotiazem ether) anilinechloride in water by dropping hydrogen peroxide oxidation, obtain
1-amino-2-(isopropyl sulphonyl) benzene crude product, then by adjusting pH, extracting, become salt, free obtain 1-amino-2-(isopropyl sulphur
Acyl) benzene sterling；
Wherein, hydrogen peroxide is 2.0～4.0 with the mol ratio of 2-(iprotiazem ether) anilinechloride, and extractant is first
One in benzene, ethyl acetate, dichloromethane or methyl tertiary butyl ether(MTBE), salt-forming reagent is 30% acidic alcohol or 30% hydrochloric acid first
Alcohol and be 1.0～1.5 with the mol ratio of 2-(iprotiazem ether) anilinechloride, free required alkali equivalent and 2-(iprotiazem
Ether) mol ratio of anilinechloride is 1.0～1.5.
Further, the aprotic polar solvent in step described in technique scheme (1) be DMF reaction temperature be 25
DEG C, the response time is 2-3h, described in enter water extraction extractant be toluene, ethyl acetate, dichloromethane or methyl tertiary butyl ether(MTBE)
In one；In described step (2), post processing extractant is in toluene, ethyl acetate, dichloromethane or methyl tertiary butyl ether(MTBE)
One, hydrochloric acid is 36.5% concentrated hydrochloric acid, described solvent extraction, become salt temperature be 25 DEG C；Needed for described step (3) is dissociated
Alkali is sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, triethylamine or N, in N-diisopropylethylamine
Kind, the mass concentration of hydrogen peroxide is 30%.
Beneficial effect: technical scheme is by splicing, reduce, aoxidizing prepared product, particularly as follows: first synthesize 2-
(iprotiazem ether) Nitrobenzol (with reference to the synthesis of this author CN this compound of 104592068A), changes highly basic sodium hydride into by alkali,
Being substantially reduced reaction temperature, improve reaction rate, process the crude product obtaining 2-(iprotiazem ether) Nitrobenzol, crude product need not pure
Change direct iron powder reducing, become salt, obtain 2-(iprotiazem ether) anilinechloride, finally at water oxygen, become salt, free obtain
Target product, this synthetic method is relatively simple, sewage quantity is less, energy consumption is relatively low, and production cost is relatively low, prepare the purity of product relatively
Height, yield are higher, it is easy to industrialized production, and suitable further genralrlization is applied.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention will be further described, but the present invention is not limited to following embodiment.
The synthesis case of compound B
Embodiment one
In the reaction bulb being furnished with liquid caustic soda device for absorbing tail gas, addition DMF (423.3g), 60% sodium hydride (44g,
1.1moL), o-fluoronitrobenzene (141.1g, 1.0moL), cryosel bath be down to less than 0 DEG C, dropping isopropyl mercaptan (91.4g,
1.2moL), completion of dropwise addition, it is back to 25 DEG C of reactions 2.0～3.0h, middle control o-fluoronitrobenzene disappears, and reaction terminates, and is delayed by reactant liquor
Slowly pouring into (1.41kg) in frozen water, toluene (280ml*3) extracts, organic solvent, washing layering, is dried, is concentrated to give 209gization
The crude product of compound B, yield 105.9%, HPLC area normalization method 98.3%.
Embodiment two
In the reaction bulb being furnished with liquid caustic soda device for absorbing tail gas, addition DMF (564.4g), 60% sodium hydride (48g,
1.2moL), o-fluoronitrobenzene (141.1g, 1.0moL), cryosel is bathed and is down to less than 0 DEG C, drips isopropyl mercaptan (99g, 1.3moL),
Completion of dropwise addition, is back to 25 DEG C of reactions 2.0～3.0h, and middle control o-fluoronitrobenzene disappears, and reaction terminates, and reactant liquor is poured slowly into ice
In water (1.41kg), ethyl acetate (280ml*3) extracts, organic solvent, washing layering, is dried, is concentrated to give 212g compound B
Crude product, yield 107.4%, HPLC area normalization method 98.5%.
Embodiment three
In the reaction bulb being furnished with liquid caustic soda device for absorbing tail gas, addition DMF (564.4g), 60% sodium hydride (60g,
1.5moL), o-fluoronitrobenzene (141.1g, 1.0moL), cryosel bath be down to less than 0 DEG C, dropping isopropyl mercaptan (114.2g,
1.5moL), completion of dropwise addition, it is back to 25 DEG C of reactions 2.0～3.0h, middle control o-fluoronitrobenzene disappears, and reaction terminates, and is delayed by reactant liquor
Slowly pouring into (1.41kg) in frozen water, dichloromethane (280ml*3) extracts, organic solvent, washing layering, is dried, is concentrated to give
The crude product of 210g compound B, yield 106.4%, HPLC area normalization method 98.3%.
Embodiment four
In the reaction bulb being furnished with liquid caustic soda device for absorbing tail gas, addition DMF (1128.8g), 60% sodium hydride (80g,
2.0moL), o-fluoronitrobenzene (141.1g, 1.0moL), cryosel bath be down to less than 0 DEG C, dropping isopropyl mercaptan (114.2g,
1.5moL), completion of dropwise addition, it is back to 25 DEG C of reactions 2.0～3.0h, middle control o-fluoronitrobenzene disappears, and reaction terminates, and is delayed by reactant liquor
Slowly pouring into (2.82kg) in frozen water, methyl tertiary butyl ether(MTBE) (280ml*3) extracts, organic solvent, washing layering, is dried, is concentrated to give
To the crude product of 208g compound B, yield 105.4%, HPLC area normalization method 98.6%.
The synthesis case of compound C
Embodiment five
In the reaction bulb being furnished with condensing tube, addition water (900g), compound B (197.2g, 1.0mol), iron powder (28g,
0.5mol), 36.5% concentrated hydrochloric acid (32g, 0.32mol), it is warming up to 80 degree of reactions, reaction terminates, and is cooled to 25 degree, adds toluene
(1L), stirring 0.5h, paving kieselguhr filters, and filter cake toluene (200ml) washs, and stratification separates toluene layer, and 25 degree to first
Benzene layer drips, 30% acidic alcohol (121.7g, 1.0mol), drip off stirring 1.0h, filter, dry and obtain 173.5g compound
C, yield 85.1%, HPLC area normalization method 97.6%.
Embodiment six
In the reaction bulb being furnished with condensing tube, addition water (900g), compound B (197.2g, 1.0mol), iron powder (112g,
2.0mol), 36.5% concentrated hydrochloric acid (64g, 0.64mol), it is warming up to 90 degree of reactions, reaction terminates, and is cooled to 25 degree, adds acetic acid
Ethyl ester (1L), stirs 0.5h, and paving kieselguhr filters, and filter cake ethyl acetate (200ml) is washed, and stratification separates toluene layer,
25 degree drip in toluene layer, 30% acidic alcohol (146.0g, 1.2mol), drip off stirring 1.0h, filter, and drying obtains
178.2g compound C, yield 87.4%, HPLC area normalization method 98.1%.
Embodiment seven
In the reaction bulb being furnished with condensing tube, add water (900g), compound B (197.2g, 1.0mol), iron powder
(179.2g, 3.2mol), 36.5% concentrated hydrochloric acid (96g, 0.96mol), it is warming up to 100 degree of reactions, reaction terminates, and is cooled to 25
Degree, adds methyl tertiary butyl ether(MTBE) (1L), stirs 0.5h, and paving kieselguhr filters, and filter cake methyl tertiary butyl ether(MTBE) (200ml) washs,
Stratification, separates toluene layer, and 25 degree drip in toluene layer, and 30% hydrochloric acid methanol (190.5g, 1.5mol) drips off stirring
1.0h, filters, and dries and obtains 176.3g compound C, yield 86.5%, HPLC area normalization method 97.8%.
The synthesis case of compound D
Embodiment eight
In reaction bulb, add water (1000g), compound C (203.7g, 1mol), 25 degree of dropping 30% hydrogen peroxide
(226.7g, 2.0mol), reaction, to terminating, with 30% sodium hydroxide regulation PH=9, extracts by ethyl acetate (200ml*3).?
Under 25 degree, drip 30% acidic alcohol (158.2,1.3mol) to ethyl acetate layer, drip off stirring 1.0h, be filtrated to get wet product.
Wet product is transferred in reaction bulb, adds water (1000g), 25 degree of lower droppings 30% sodium hydroxide (146.7g, 1.1mol), drip off
Stirring 0.5h, filters, and water washs, and dries and obtains 170.2g sterling compound D, yield 85.4%, HPLC area normalization method
99.2%.
Embodiment nine
In reaction bulb, add water (1000g), compound C (203.7g, 1mol), 25 degree of dropping 30% hydrogen peroxide
(340g, 3.0mol), reaction, to terminating, with 30% sodium hydroxide regulation PH=9, extracts with toluene (200ml*3).At 25 degree
Under, drip 30% acidic alcohol (133.8,1.1mol) to toluene layer, drip off stirring 1.0h, be filtrated to get wet product.Wet product is turned
Move in reaction bulb, add water (1000g), 25 degree of lower droppings 30% potassium hydroxide (242.7g, 1.3mol), drip off stirring
0.5h, filters, and water washs, and dries and obtains 173.2g sterling compound D, yield 86.9%, HPLC area normalization method 99.4%.
Embodiment ten
In reaction bulb, add water (1000g), compound C (203.7g, 1mol), 25 degree of dropping 30% hydrogen peroxide
(453g, 4.0mol), reaction, to terminating, with 30% sodium hydroxide regulation PH=9, extracts with dichloromethane (200ml*3).25
Under degree, drip 30% hydrochloric acid methanol (182.5,1.5mol) to dichloromethane layer, drip off stirring 1.0h, be filtrated to get wet product.Will
Wet product is transferred in reaction bulb, adds water (1000g), 25 degree of lower droppings 30% potassium carbonate (691.0g, 1.5mol), drips off stirring
0.5h, filters, and water washs, and dries and obtains 1768.5g sterling compound D, yield 84.5%, HPLC area normalization method
99.3%.
Embodiment 11
In reaction bulb, add water (1000g), compound C (203.7g, 1mol), 25 degree of dropping 30% hydrogen peroxide
(283.3g, 2.5mol), reaction, to terminating, with 30% sodium hydroxide regulation PH=9, extracts with methyl tertiary butyl ether(MTBE) (200ml*3)
Take.At 25 degrees c, drip 30% acidic alcohol (133.8,1.1mol) to methyl tert-butyl ether layers, drip off stirring 1.0h, filter
Obtain wet product.Wet product is transferred in reaction bulb, adds water (1000g), under 25 degree, drip triethylamine (121.2g, 1.2mol),
Dripping off stirring 0.5h, filter, water washs, and dries and obtains 175.6g sterling compound D, yield 88.1%, HPLC area normalization
Method 99.4%.
Above-described embodiment, only for technology design and the feature of the explanation present invention, its object is to allow person skilled in the art
Scholar will appreciate that present disclosure and is carried out, and can not limit the scope of the invention with this, all according to the present invention
The equivalence that spirit is made changes or modifies, and all should contain within the scope of the present invention.
Claims (4)
1. a synthetic method for cancer therapy drug Ceritinib intermediate 1-amino-2-(isopropyl sulphonyl) benzene, is characterized in that: should
Synthetic method comprises the steps:
1) in aprotic polar solvent, o-fluoronitrobenzene and sodium hydride, temperature control-1～1 DEG C of dropping isopropyl mercaptan, dropping are added
After end in 0～25 DEG C of reaction to o-fluoronitrobenzene reaction completely, post processing enters water extraction, is concentrated to give crude product 2-(iprotiazem
Ether) Nitrobenzol；
Wherein, aprotic polar solvent is 3.0～8.0 with the mass ratio of o-fluoronitrobenzene, and sodium hydride rubs with o-fluoronitrobenzene
Your ratio is 1.1～2.0, and isopropyl mercaptan is 1.2～1.5 with the mol ratio of o-fluoronitrobenzene；
2) by step (1) gained 2-(iprotiazem ether) Nitrobenzol in water with iron powder, hydrochloric acid reduction, terminate rear solvent extraction,
Salt is become to obtain 2-(iprotiazem ether) anilinechloride；
Wherein, iron powder is 0.5～3.2 with the mol ratio of 2-(iprotiazem ether) Nitrobenzol, and reaction temperature is 80～100 DEG C, salt
Acid is 0.32～0.96 with the mol ratio of 2-(iprotiazem ether) Nitrobenzol, and salt-forming reagent is 30% acidic alcohol or 30% hydrochloric acid
Methanol, salt-forming reagent is 1.0～1.5 with the mol ratio of 2-(iprotiazem ether) Nitrobenzol；
3) by step (2) gained 2-(iprotiazem ether) anilinechloride in water by dropping hydrogen peroxide oxidation, obtain 1-ammonia
Base-2-(isopropyl sulphonyl) benzene crude product, then by adjusting pH, extracting, become salt, free obtain 1-amino-2-(isopropyl sulphonyl) benzene
Sterling；
Wherein, hydrogen peroxide is 2.0～4.0 with the mol ratio of 2-(iprotiazem ether) anilinechloride, and extractant is toluene, second
One in acetoacetic ester, dichloromethane or methyl tertiary butyl ether(MTBE), salt-forming reagent be 30% acidic alcohol or 30% hydrochloric acid methanol and
It is 1.0～1.5 with the mol ratio of 2-(iprotiazem ether) anilinechloride, free required alkali equivalent and 2-(iprotiazem ether)
The mol ratio of anilinechloride is 1.0～1.5.
A kind of cancer therapy drug Ceritinib intermediate 1-amino-2-(isopropyl sulphonyl) benzene the most according to claim 1
Synthetic method, is characterized in that: the aprotic polar solvent in described step (1) is DMF, and reaction temperature is 25 DEG C, the response time
For 2-3h, described in enter water extraction extractant be the one in toluene, ethyl acetate, dichloromethane or methyl tertiary butyl ether(MTBE).
A kind of cancer therapy drug Ceritinib intermediate 1-amino-2-(isopropyl sulphonyl) benzene the most according to claim 1
Synthetic method, is characterized in that: in described step (2), post processing extractant is toluene, ethyl acetate, dichloromethane or methyl-tert
One in butyl ether, hydrochloric acid is 36.5% concentrated hydrochloric acid, and described solvent extraction, one-tenth salt temperature are 25 DEG C.
A kind of cancer therapy drug Ceritinib intermediate 1-amino-2-(isopropyl sulphonyl) benzene the most according to claim 1
Synthetic method, is characterized in that: in described step (3), free required alkali is sodium hydroxide, potassium hydroxide, sodium carbonate, bicarbonate
One in sodium, potassium carbonate, triethylamine or DIPEA, the mass concentration of hydrogen peroxide is 30%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610403800.7A CN106083670A (en) | 2016-06-08 | 2016-06-08 | The synthetic method of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610403800.7A CN106083670A (en) | 2016-06-08 | 2016-06-08 | The synthetic method of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106083670A true CN106083670A (en) | 2016-11-09 |
Family
ID=57228922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610403800.7A Pending CN106083670A (en) | 2016-06-08 | 2016-06-08 | The synthetic method of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106083670A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112062699A (en) * | 2020-11-13 | 2020-12-11 | 苏州开元民生科技股份有限公司 | Preparation method of o-aminothiophenol |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104356112A (en) * | 2014-10-30 | 2015-02-18 | 南京奇可医药化工有限公司 | Method for preparing ceritinib |
| WO2015060373A1 (en) * | 2013-10-23 | 2015-04-30 | 中外製薬株式会社 | Quinazolinone and isoquinolinone derivative |
| CN105085483A (en) * | 2015-06-04 | 2015-11-25 | 湖北生物医药产业技术研究院有限公司 | Kinase inhibitor and application thereof |
-
2016
- 2016-06-08 CN CN201610403800.7A patent/CN106083670A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015060373A1 (en) * | 2013-10-23 | 2015-04-30 | 中外製薬株式会社 | Quinazolinone and isoquinolinone derivative |
| CN104356112A (en) * | 2014-10-30 | 2015-02-18 | 南京奇可医药化工有限公司 | Method for preparing ceritinib |
| CN105085483A (en) * | 2015-06-04 | 2015-11-25 | 湖北生物医药产业技术研究院有限公司 | Kinase inhibitor and application thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112062699A (en) * | 2020-11-13 | 2020-12-11 | 苏州开元民生科技股份有限公司 | Preparation method of o-aminothiophenol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104892509B (en) | Nuo get Si Ta preparation method | |
| CN105111205B (en) | A kind of preparation method of Pa Boxini | |
| CN110194776A (en) | A kind of synthetic method of Rui Lugeli | |
| CN108017583A (en) | A kind of preparation method for winning U.S. | |
| CN104402946B (en) | Canagliflozin intermediate and its unbodied preparation method | |
| CN103012167A (en) | Preparation method of ambroxol hydrochloride | |
| CN104774196B (en) | A kind of preparation method of benzimidizole derivatives | |
| CN103030629B (en) | Method for preparing fasudil hydrochloride | |
| CN104496964A (en) | Industrial production method of esomeprazole | |
| CN106083670A (en) | The synthetic method of cancer therapy drug Ceritinib intermediate 1 amino 2 (isopropyl sulphonyl) benzene | |
| CN104098505A (en) | Preparation method for saxagliptin | |
| CN103936638B (en) | The synthetic method of florfenicol | |
| CN105399667A (en) | Preparation method of edoxaban intermediate | |
| CN104961756A (en) | Preparation method of (S)-Boc-4-dihydroxyborylphenylalanine | |
| CN105130887A (en) | Regorafenib preparation method | |
| CN111004221A (en) | Pyrimidine/benzimidazole heterozygote, preparation method and medical application | |
| CN106916147A (en) | Compound and its production and use | |
| CN108440623A (en) | A kind of preparation method and products thereof of capecitabine intermediate | |
| CN104945434B (en) | (2 ﹣ bis- substitution phosphines phenyl) -1- alkyl-indols Phosphine ligands and its synthetic method and application | |
| CN113717053A (en) | Synthesis method of key intermediate of tyrosine kinase inhibitor | |
| CN105777852A (en) | Deflazacort synthetic method | |
| CN105481842A (en) | Method for preparing olmesartan medoxomil | |
| CN103992306B (en) | A kind of preparation of Levpantoprazole Sodium and process for purification | |
| CN106083689A (en) | A kind of new preparation process of Silodosin compound | |
| CN103030599B (en) | Gefitinib intermediate and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161109 |
|
| WD01 | Invention patent application deemed withdrawn after publication |