CN106083762A - Fertile a kind of preparation method for western spit of fland intermediate - Google Patents
Fertile a kind of preparation method for western spit of fland intermediate Download PDFInfo
- Publication number
- CN106083762A CN106083762A CN201610607100.XA CN201610607100A CN106083762A CN 106083762 A CN106083762 A CN 106083762A CN 201610607100 A CN201610607100 A CN 201610607100A CN 106083762 A CN106083762 A CN 106083762A
- Authority
- CN
- China
- Prior art keywords
- preparation
- methyl
- iii
- preparing
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims abstract description 15
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 12
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical group BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 4
- 238000006482 condensation reaction Methods 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- PNJYPDSNILRAGQ-UHFFFAOYSA-N CC1=C(C=CC=C1)C.S1C=CC(=C1)O Chemical compound CC1=C(C=CC=C1)C.S1C=CC(=C1)O PNJYPDSNILRAGQ-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 1
- 235000021050 feed intake Nutrition 0.000 claims 1
- RMVRSNDYEFQCLF-UHFFFAOYSA-N phenyl mercaptan Natural products SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- -1 thiophenol dimethyl benzenes Chemical class 0.000 abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 208000024714 major depressive disease Diseases 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical group C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 2
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- KQZFLCYOCXDFBQ-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)sulfanylphenyl]-3-methylpiperazine Chemical compound C1CNC(C)CN1C1=CC=CC=C1SC1=CC=C(Cl)C=C1 KQZFLCYOCXDFBQ-UHFFFAOYSA-N 0.000 description 1
- DEFBBVSVIMXNCP-UHFFFAOYSA-N 2-(3-methylpiperazin-1-yl)aniline Chemical compound C1CNC(C)CN1C1=CC=CC=C1N DEFBBVSVIMXNCP-UHFFFAOYSA-N 0.000 description 1
- CTIWLHPJOBRVCP-UHFFFAOYSA-N 4-chlorobenzenethiol copper Chemical compound [Cu].SC1=CC=C(Cl)C=C1 CTIWLHPJOBRVCP-UHFFFAOYSA-N 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960002263 vortioxetine Drugs 0.000 description 1
- YQNWZWMKLDQSAC-UHFFFAOYSA-N vortioxetine Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 YQNWZWMKLDQSAC-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to the fertile synthesis technique field for western spit of fland intermediate.Its preparation process includes: adjacent bromo-iodobenzene (II) and N methyl piperazine (III) occur condensation reaction to generate 2 (1 methyl piperazine base) bromobenzene (IV) in the basic conditions, 2 (1 methyl piperazine base) bromobenzene (IV) is in the basic conditions with 2,4 thiophenol dimethyl benzenes (V) reaction obtains 1 methyl 4 [2 (2,4 aminomethyl phenyl sulfenyl)] piperazine (I).
Description
Technical field
The invention belongs to drug research field, be specifically related to the synthesis technique that a kind of antidepressants irrigate for western spit of fland intermediate and grind
Study carefully.
Background technology
Irrigate and belong to a new generation's antidepressants for Xi Ting, be exploited for the treatment of major depressive disorder patient.This medicine is considered
Combined by two kinds of mechanism of action and play a role: receptor active regulation and reuptake suppress (reuptakeinhibition).Body
Outer research shows, fertile is 5-HT for Xi Ting3And 5-HT7 Receptor antagonist, 5-HT1B acceptor portion agonist, 5-HT1A receptor
Agonist, serotonin transporter (SERT) inhibitor.Internal non-clinical study shows, fertile to strengthen brain for western spit of fland specific
Regional nerve neurotransmitter serotonin, norepinephrine, dopamine, acetylcholine, the level of histamine.The fertile multimode for Xi Ting
Formula role attribute (multimodal activity profile), is expected to existing medicine to be used to fail fully to control for those
The major depressive disorder patient of system brings clinical benefit.
Military field (Takeda) is announced with Ling Bei (Lundbeck), have submitted its New Multi-mode antidepressants to FDA and irrigates
For the new drug application (NDA) of Xi Ting (Lu AA21004), for the treatment of major depressive disorder (MDD) adult patient.If obtained
Batch, military field and Ling Bei plan to combine this medicine of release in the U.S. and Japan.
The piperazine that the ferrocene complex of Chinese patent CN02819025 o-dichlorohenzene and resin are protected reacts to be irrigated
For western spit of fland intermediate, then with 2,4-thiophenol dimethyl benzene reacts, and then obtains product by illumination solution complexation, resin fracture.Should
Method step is long, needs to use the dangerous toxic reagents such as ferrocene, and yield is the lowest, and final step reaction yield only has 14%,
Be not suitable for large-scale industrial production.
Chinese patent CN02819025 is it is also mentioned that analog 1-[2-(4-chlorophenyl sulfanyl) phenyl]-3-methyl piperazine
Synthesis, is obtained by reacting with 4-chlorothio phenol copper after 2-(3-methylpiperazine-1-yl) aniline diazotising, but yield is the lowest,
Only 11%, be not suitable for large-scale production.
Summary of the invention
The purpose of the present invention is that provides a kind of new the fertile of industrialized production that be suitable for convenient, that yield is higher to replace
Western spit of fland intermediate preparation method.
For achieving the above object, present invention employs following main technical schemes:
Fertile for western spit of fland intermediate (I)
Its preparation process includes: adjacent bromo-iodobenzene (II) occurs condensation reaction to generate with N methyl piperazine (III) in the basic conditions
2-(1-methyl piperazine base) bromobenzene (IV), 2-(1-methyl piperazine base) bromobenzene (IV) in the basic conditions with 2,4-dimethyl benzene sulfur
Phenol (V) reaction obtains 1-methyl 4-[2-(2,4-aminomethyl phenyl sulfenyl)] piperazine (I).
In above formula, (II) and (III) when preparing (IV), reaction dissolvent is selected from toluene, dimethyl sulfoxide or N, N-diformazan
Base Methanamide；Alkali is sodium tert-butoxide, sodium hydroxide, potassium hydroxide, potassium carbonate；Reaction temperature is 100 DEG C～118 DEG C；(II) and
(III) mol ratio is 1:1～1:2.5.
In above formula, (IV) and (V) when preparing (I), the mol ratio of compound (IV) and (V) is 1:1.0～1:1.5；Instead
Answering solvent is toluene or DMF；Alkali is sodium tert-butoxide, sodium hydroxide, potassium hydroxide, potassium carbonate；Catalyst is Pddba2 and rac-
BINAP or Pd2dba3 and rac-BINAP.
Below in conjunction with preferred embodiment, technical solution of the present invention is further non-limitingly described in detail.
It is embodied as case
The preparation of embodiment 1:2-(1-methyl piperazine base) bromobenzene (IV)
5.0g neighbour's bromo-iodobenzene (II) (17.7mmol), 1.86g N methyl piperazine (III) (18.6mmol), 3.0g potassium carbonate
(35.4mmol) in toluene (50ml), return stirring 3h is complete to reaction, and add water (50ml), sucking filtration, separatory, organic layer salt
Washing, is dried, and concentrates, obtains yellow oil 3.8g, yield 84.4%.
The preparation of embodiment 2:1-methyl 4-[2-(2,4-aminomethyl phenyl sulfenyl)] piperazine (I)
By 0.16gPd (dba) 2 (1.14mmol), 0.36g rac-BINAP (0.58mmol), 50mL toluene and uncle 16.14g
Sodium butoxide (168mmol) is sequentially added in 100mL there-necked flask, opens stirring, then by 5.0g 2-(1-methyl piperazine base) bromobenzene
(IV) (19.7mmol), 2.86g 2,4-thiophenol dimethyl benzene (V) (20.7mmol) adds reactant liquor, and return stirring 24h is to instead
Should be complete, add water (50ml), sucking filtration, separatory, and organic layer salt is washed, and is dried, is concentrated to dryness, obtains 1-methyl 4-[2-(2,4-
Aminomethyl phenyl sulfenyl)] piperazine 5.8g, brown oily, yield 94.3%.
Claims (6)
1. prepare the fertile method for western spit of fland intermediate (I) for one kind, it is characterised in that: adjacent bromo-iodobenzene (II) and N methyl piperazine
(III) condensation reaction is occurred to generate 2-(1-methyl piperazine base) bromobenzene (IV), 2-(1-methyl piperazine base) bromine in the basic conditions
Benzene (IV) is in the basic conditions with 2, and 4-thiophenol dimethyl benzene (V) reaction obtains formula (I) 1-methyl 4-[2-(2,4-aminomethyl phenyl
Sulfenyl)] piperazine.
2. concrete route is as follows:
。
Preparation method the most according to claim 1, (II) and (III) when preparing (IV) reaction dissolvent selected from toluene, two
Methyl sulfoxide or N, N-dimethylformamide；Alkali is sodium tert-butoxide, sodium hydroxide, potassium hydroxide, potassium carbonate；Reaction temperature is
100 DEG C～118 DEG C.
Preparation method the most according to claim 1, (II) and (III) when preparing (IV), (II) and the rate of charge of (III)
For 1:1～1:1.5.
Preparation method the most according to claim 1, (IV) and (V), when preparing (I), compound (IV) and (V) feed intake
Ratio is 1:1.0～1:1.5.
Preparation method the most according to claim 1, (IV) and (V), when preparing (I), reaction dissolvent is toluene or DMF；Alkali
For sodium tert-butoxide, sodium hydroxide, potassium hydroxide, potassium carbonate；Catalyst is Pd (dba)2And rac-BINAP.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610607100.XA CN106083762A (en) | 2016-07-29 | 2016-07-29 | Fertile a kind of preparation method for western spit of fland intermediate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610607100.XA CN106083762A (en) | 2016-07-29 | 2016-07-29 | Fertile a kind of preparation method for western spit of fland intermediate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106083762A true CN106083762A (en) | 2016-11-09 |
Family
ID=57478579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610607100.XA Pending CN106083762A (en) | 2016-07-29 | 2016-07-29 | Fertile a kind of preparation method for western spit of fland intermediate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106083762A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109438391A (en) * | 2018-11-26 | 2019-03-08 | 合肥创新医药技术有限公司 | A kind of preparation method of hydrobromic acid Vortioxetine impurity |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016004908A1 (en) * | 2014-07-08 | 2016-01-14 | Zentiva, K.S. | Method of preparing vortioxetine |
| CN105541759A (en) * | 2016-01-07 | 2016-05-04 | 美吉斯制药（厦门）有限公司 | Novel method for preparing vortioxetine |
| CN105622546A (en) * | 2016-01-07 | 2016-06-01 | 美吉斯制药（厦门）有限公司 | Preparation method for vortioxetine |
-
2016
- 2016-07-29 CN CN201610607100.XA patent/CN106083762A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016004908A1 (en) * | 2014-07-08 | 2016-01-14 | Zentiva, K.S. | Method of preparing vortioxetine |
| CN105541759A (en) * | 2016-01-07 | 2016-05-04 | 美吉斯制药（厦门）有限公司 | Novel method for preparing vortioxetine |
| CN105622546A (en) * | 2016-01-07 | 2016-06-01 | 美吉斯制药（厦门）有限公司 | Preparation method for vortioxetine |
Non-Patent Citations (1)
| Title |
|---|
| SHIMODA, YOKO，ET AL: "Synthesis and evaluation of 1-[2-(4-[11C]methoxyphenyl)phenyl]piperazine for imaging of the serotonin 5-HT7 receptor in the rat brain", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109438391A (en) * | 2018-11-26 | 2019-03-08 | 合肥创新医药技术有限公司 | A kind of preparation method of hydrobromic acid Vortioxetine impurity |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103788019B (en) | The fertile preparation method for Xi Ting | |
| CN103992262B (en) | Sai Rui replaces the preparation method of Buddhist nun and intermediate thereof | |
| AU2011281421A1 (en) | Process for preparing aminobenzoylbenzofuran derivatives | |
| JPS6210990B2 (en) | ||
| CN104230852A (en) | Synthetic method of vortioxetine | |
| CN105061414B (en) | One kettle way prepares Brexpiprazole | |
| CN105461704A (en) | Preparing method for brexpiprazole | |
| JP5873484B2 (en) | Dronedarone and method for producing the salt thereof | |
| CN105622546A (en) | Preparation method for vortioxetine | |
| CN105198821B (en) | Lip river former times replaces the preparation method of Buddhist nun | |
| CN106632033A (en) | Preparation method of lenvatinib | |
| US20160311777A1 (en) | Method for preparing nilotinib intermediate | |
| CN104628676A (en) | Preparation method of Vortioxetine | |
| CN106083762A (en) | Fertile a kind of preparation method for western spit of fland intermediate | |
| CN105348220A (en) | Synthetic method for vortioxetine hydrobromide | |
| EA024767B1 (en) | Sulphonamide derivatives of benzylamine for the treatment of cns diseases | |
| CN105566260A (en) | Furosemide preparation method | |
| US20210317107A1 (en) | Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase | |
| WO2019178480A1 (en) | Pyrazole-containing macrophage migration inhibitory factor inhibitors | |
| CN103755636A (en) | Method for synthesizing Lorcaserin raceme derivative | |
| US9688685B2 (en) | Method for preparing volasertib and intermediate thereof | |
| CN102249962B (en) | Preparation method of 1,1-disulfur-1-olefin | |
| NO852814L (en) | ACETYLENIC PHENOXYPROPANOLE DERIVATIVES. | |
| CN104016898A (en) | 3,4-disubstituted pyrrole compound as well as preparation method and application thereof | |
| CN109678900B (en) | Sulfanilamide derivative and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161109 |