CN105566367B - A kind of synthesis N replaces the method for the borate of 1,2,5,6 tetrahydropyridine 4 - Google Patents
A kind of synthesis N replaces the method for the borate of 1,2,5,6 tetrahydropyridine 4 Download PDFInfo
- Publication number
- CN105566367B CN105566367B CN201610014644.5A CN201610014644A CN105566367B CN 105566367 B CN105566367 B CN 105566367B CN 201610014644 A CN201610014644 A CN 201610014644A CN 105566367 B CN105566367 B CN 105566367B
- Authority
- CN
- China
- Prior art keywords
- tetrahydropyridine
- replaces
- halogen
- synthesis
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Abstract
The invention discloses a kind of method that synthesis N replaces the borate of 1,2,5,6 tetrahydropyridine 4.4 piperidones are replaced as raw material using N, carbonyl is transformed into alkenyl halogen with the reaction of the aromatic ester of phosphorous acid three, halogen and organic base, then the N substitution borates of 1,2,5,6 tetrahydropyridine 4 are obtained with isopropylmagnesium chloride lithium chloride and alkoxy borate esters reaction.This method raw material is easy to get, easy to operate, and product purity is high, it is to avoid previous methods need ultralow temperature and the palladium chtalyst to be coupled, and with implicit costs and route advantage, improve such competitiveness of product in market.
Description
Technical field
The present invention relates to a kind of method that synthesis N- replaces -1,2,5,6- tetrahydropyridine -4- borates, belong in the middle of medicine
Body synthesizes field.
Background technology
In new drug development field, the Suzuki coupling reactions of palladium chtalyst apply increasing in document and patent.Its
In, such as I type sodium hydrogen exchanger (abbreviation NHE-1) inhibitor also relatively conventional with piperidines construction unit pharmaceutical activity intermediate
1 and fatty acid amide hydrolase (abbreviation FAAH) inhibitor 2 etc..The synthesis of these compounds generally all replaces -1 using N-,
After the coupling of 2,5,6- tetrahydropyridine -4- borates palladium chtalysts, then hydrogenate the piperidine structure unit needed for obtaining.
At present, N- replace -1,2,5,6- tetrahydropyridine -4- borates synthesis be mainly:From N- substitution -4- piperidones,
First generate after alkenyl triflate, column chromatography for separation, then exist with LDA or LiHMDS and PhNTf2 reactions under ultralow temperature
With obtaining product after the coupling of connection boron ester again column chromatography under palladium chtalyst.
The above method has the following disadvantages:Ultralow temperature is needed, while being coupled using expensive Metal Palladium, is purified
Column chromatography is needed, these all limit the amplification production of synthesis technique.
The content of the invention
In order to overcome drawbacks described above, replace -1,2,5,6- tetrahydropyridine -4- borates the invention discloses one kind synthesis N-
Method.- 4- piperidones is replaced as raw material using N-, with P (OR)3、X2Carbonyl is transformed into alkenyl halogen with organic base reaction, then
WithiCrude product is obtained after-PrMgCl-LiCl and alkoxy borate esters reaction, N- substitutions -1,2,5,6- are obtained after mixed solvent mashing
Tetrahydropyridine -4- borate sterlings, GC and nuclear-magnetism purity more than 98%.
One kind synthesis N- replaces the method for -1,2,5,6- tetrahydropyridine -4- borates, it is characterised in that including following step
Suddenly:
The first step:Replace -4- piperidones, the aromatic ester of phosphorous acid three and organic base to be dissolved in dichloromethane solvent N-, control
- 25 DEG C to -15 DEG C of temperature, is added dropwise halogen, insulated and stirred reaction.After completion of the reaction, solvent distillation, is subsequently added cold 95% ethanol and stirs
After mixing, solid is filtered out, filtrate is evaporated, add toluene and water stratification, toluene layer saturated common salt water washing, be spin-dried for organic solvent molten
Agent obtains N- substitution -1,2,5,6- tetrahydropyridine -4- halogen;
Second step:Isopropylmagnesium chloride-lithium chloride is added into anhydrous ether solvent, -15 DEG C to 0 DEG C of temperature control is added dropwise N- and taken
- 1,2,5,6- tetrahydropyridine -4- halogen of generation, addition finishes stirring 1-2 hours, after exchange terminates, is subsequently added into alkoxy borate esters,
Then keep 0 DEG C to 80 DEG C reaction.Cooling, adds 5-15% aqueous hydrochloric acid solutions and reaction is quenched, and adds ethyl acetate layering, organic
Layer saturated common salt washing, after organic layer is evaporated, adds and -1,2,5,6- tetrahydropyridine -4- of N- substitutions is obtained after mixed solvent mashing
Borate sterling, GC and nuclear-magnetism purity more than 98%, two step yields:55-63%.
Further, in the above-mentioned technical solutions, in first step N- substitutions -4- piperidones, the upper substituents of N be selected from Boc,
Cbz, methyl, ethyl, isopropyl or benzyl.
Further, in the above-mentioned technical solutions, in the first step, the aromatic ester of phosphorous acid three is selected from triphenyl phosphite, phosphorous
Sour three (4- ethylo benzenes) esters or phosphorous acid three (4- cumenes) ester.
Further, in the above-mentioned technical solutions, in the first step, organic base is selected from triethylamine or diisopropyl ethyl amine.
Further, in the above-mentioned technical solutions, in the first step, halogen is selected from bromine or iodine.
Further, in the above-mentioned technical solutions, in the first step, in the first step, N- substitution -4- piperidones, phosphorous acid three
Aromatic ester, organic base and halogen equivalent proportion are 1:1-2.5:1-5:1-2.5.
Further, in the above-mentioned technical solutions, in second step, anhydrous ether solvent is selected from tetrahydrofuran or 2- methyl four
Hydrogen furans.
Further, in the above-mentioned technical solutions, in second step, alkoxy borate esters are selected from methoxy ylboronic acid pinacol
Ester, isopropoxy pinacol borate, methoxy ylboronic acid DOPCP or isopropoxy boric acid DOPCP.
Further, in the above-mentioned technical solutions, in second step, N- replaces -1,2,5,6- tetrahydropyridine -4- halogen, isopropyl
Base magnesium chloride-lithium chloride is 1 with alkoxy borate esters equivalent proportion:1-1.5:1-2.
In the above-mentioned technical solutions, in the above-mentioned technical solutions, in second step, mixed solvent is selected from normal heptane or n-hexane
Mixed with ethanol according to different proportion.
The beneficial effect of invention
This method raw material is easy to get, without column chromatography, easy to operate, product purity is high, it is to avoid previous methods need ultralow
Gentle palladium chtalyst coupling, with implicit costs and route advantage, is more suitable for industrialized production, is conducive to improving the city of such product
Field competitiveness.
Specific embodiment
Embodiment 1
N- methyl isophthalic acids, the synthesis of 2,5,6- tetrahydropyridine -4- pinacol borates:
The first step:In reaction bulb, by N- methyl -4- piperidones (11.3g, 0.1mol), triphenyl phosphite (37.2g,
0.12mol) it is dissolved in triethylamine (15.2g, 0.15mol) in 160mL dichloromethane, -25 DEG C to -20 DEG C of temperature control, bromine is added dropwise
Dichloromethane (30mL) solution of plain (19.2g, 0.12mol), completion of dropping, insulated and stirred reaction.TLC detection reactions are finished
Afterwards, vacuum distillation solvent, is subsequently added after the stirring of the cold ethanol of 300mL 95%, filters out solid, filtrate is evaporated, add 120mL first
Benzene and 40mL water stratifications, toluene layer saturated common salt water washing are spin-dried for organic solvent solvent and obtain N- methyl isophthalic acids, 2,5,6- tetrahydrochysene pyrroles
Pyridine -4- bromines, internal standard demarcation yield is 84%;
Second step:Under nitrogen protection, 1.3M isopropylmagnesium chlorides-lithium chloride (72mL, 94mmol) is added in reaction bulb,
- 15 DEG C to -10 DEG C of temperature control, is added dropwise N- methyl isophthalic acids, and tetrahydrofuran (80mL) solution of 2,5,6- tetrahydropyridine -4- bromines has been added
Finish stirring 1-2 hours.After exchange terminates, methoxyl group pinacol borate (15.8g, 0.1mol) is then added dropwise to, is then kept
Room temperature reaction is stayed overnight.Add 10% aqueous hydrochloric acid solution and reaction is quenched, adjust PH=4-5, add 150mL ethyl acetate, organic layer saturation
Salt is washed, after organic layer is evaporated, and adds ethanol/heptane 40:14.1g off-white powder N- methyl isophthalic acids are obtained after 1 mashing, 2,
5,6- tetrahydropyridine -4- boric acid pinacol esters, GC:98.3%, yield:63%.
Embodiment 2
The synthesis of N- benzyl -1,2,5,6- tetrahydropyridine -4- boric acid DOPCPs:
The first step:In reaction bulb, by N- benzyl -4- piperidones (18.9g, 0.1mol), triphenyl phosphite (37.2g,
0.12mol), diisopropyl ethyl amine (19.4g, 0.15mol) and the mixing of 160mL dichloromethane, -20 DEG C to -15 DEG C of temperature control, drop
Plus dichloromethane (30mL) solution of bromine (19.2g, 0.12mol), completion of dropping, insulated and stirred reaction.TLC detections have been reacted
Bi Hou, vacuum distillation solvent is subsequently added after the stirring of the cold ethanol of 350mL 95%, filters out solid, filtrate is evaporated, adds 130mL
Toluene and 40mL water stratifications, toluene layer saturated common salt water washing are spin-dried for organic solvent solvent and obtain N- benzyls -1,2,5,6- tetrahydrochysenes
Pyridine -4- bromines, internal standard demarcation yield is 81%;
Second step:Under nitrogen protection, 1.3M isopropylmagnesium chlorides-lithium chloride (85mL, 0.11mol) is added into reaction bulb
Interior, N- benzyls -1,2 are added dropwise in -15 DEG C to -10 DEG C of temperature control, and tetrahydrofuran (80mL) solution of 5,6- tetrahydropyridine -4- bromines is finished
Stirring 1-2 hours.After exchange terminates, methoxy ylboronic acid DOPCP (15.8g, 0.11mol) is then added dropwise to, is then kept
Room temperature reaction is stayed overnight.Add 10% aqueous hydrochloric acid solution and reaction is quenched, adjust PH=4-5, add 150mL ethyl acetate, organic layer saturation
Salt is washed, after organic layer is evaporated, and adds ethanol/heptane 30:16.2g off-white powder N- benzyl -1,2 are obtained after 1 mashing,
5,6- tetrahydropyridine -4- boric acid DOPCPs, GC:98.7%, yield:57%.
Embodiment 3
The synthesis of N-Boc-1,2,5,6- tetrahydropyridine -4- pinacol borates:
The first step:In reaction bulb, by N-Boc-4- piperidones (19.9g, 0.1mol), triphenyl phosphite (34.1g,
0.11mol) it is dissolved in triethylamine (15.2g, 0.15mol) in 160mL dichloromethane, -25 DEG C to -20 DEG C of temperature control, bromine is added dropwise
Dichloromethane (30mL) solution of plain (17.6g, 0.11mol), completion of dropping, insulated and stirred reaction.TLC detection reactions are finished
Afterwards, vacuum distillation solvent, is subsequently added after the stirring of the cold ethanol of 300mL 95%, filters out solid, filtrate is evaporated, add 150mL first
Benzene and 40mL water stratifications, toluene layer saturated common salt water washing are spin-dried for organic solvent solvent and obtain N-Boc-1,2,5,6- tetrahydrochysene pyrroles
Pyridine -4- bromines, internal standard demarcation yield is 80%;
Second step:Under nitrogen protection, 1M isopropylmagnesium chlorides-lithium chloride (88mL, 88mmol) is added in reaction bulb, control
- 15 DEG C to -5 DEG C of temperature, is added dropwise N-Boc-1, and 2- methyltetrahydrofurans (90mL) solution of 2,5,6- tetrahydropyridine -4- bromines is added
Finish stirring 1-2 hours.After exchange terminates, isopropoxy pinacol borate (16.4g, 88mmol) is then added dropwise to, then
Room temperature reaction is kept to stay overnight.Add 10% aqueous hydrochloric acid solution and reaction is quenched, adjust PH=4-5, add 160mL ethyl acetate, organic layer
Saturated common salt is washed, after organic layer is evaporated, and adds ethanol/heptane 5:18.9g needle-like white crystals N-Boc-1 are obtained after 1 mashing,
2,5,6- tetrahydropyridine -4- boric acid pinacol esters, GC:99.6%, yield:61%.
Embodiment 4
The synthesis of N-Cbz-1,2,5,6- tetrahydropyridine -4- pinacol borates:
The first step:In reaction bulb, by N-Cbz-4- piperidones (19.9g, 0.1mol), phosphorous acid three (4- ethylo benzenes) ester
(43.4g, 0.11mol) and triethylamine (15.2g, 0.15mol) are dissolved in 180mL dichloromethane, -25 DEG C to -20 DEG C of temperature control,
Dichloromethane (60mL) solution of iodine (25.4g, 0.10mol), completion of dropping, insulated and stirred reaction is added dropwise.TLC detections have been reacted
Bi Hou, vacuum distillation solvent is subsequently added after the stirring of the cold ethanol of 420mL 95%, filters out solid, filtrate is evaporated, adds 180mL
Toluene and 40mL water stratifications, toluene layer saturated common salt water washing are spin-dried for organic solvent solvent and obtain N-Cbz-1,2,5,6- tetrahydrochysenes
Pyridine -4- iodine, internal standard demarcation yield is 77%;
Second step:Under nitrogen protection, 1M isopropylmagnesium chlorides-lithium chloride (88mL, 88mmol) is added in reaction bulb, control
- 15 DEG C to -10 DEG C of temperature, is added dropwise N-Cbz-1, and 2- methyltetrahydrofurans (90mL) solution of 2,5,6- tetrahydropyridine -4- bromines is added
Finish stirring 1-2 hours.After exchange terminates, methoxyl group pinacol borate (14.2g, 90mmol) is then added dropwise to, is then protected
Room temperature reaction is held to stay overnight.Add 10% aqueous hydrochloric acid solution and reaction is quenched, adjust PH=4-5, add 220mL ethyl acetate, organic layer is satisfied
With salt washing, after organic layer is evaporated, ethanol/heptane 10 is added:19.2g light yellow solid N-Cbz-1,2 are obtained after 1 mashing,
5,6- tetrahydropyridine -4- boric acid pinacol esters, GC:99.6%, yield:56%.
Claims (5)
1. one kind synthesis N- replaces the method for -1,2,5,6- tetrahydropyridine -4- borates, it is characterised in that comprise the following steps:
The first step, -4- piperidones, the aromatic ester of phosphorous acid three and organic base is replaced to be dissolved in dichloromethane solvent the N-, temperature control -25
DEG C to -15 DEG C, the dichloromethane solution of halogen, insulated and stirred reaction is added dropwise;After completion of the reaction, solvent distillation, is subsequently added cold
After the stirring of 95% ethanol, solid is filtered out, filtrate is evaporated, add toluene and water stratification, toluene layer saturated common salt water washing, be spin-dried for
Organic solvent solvent obtains N- substitution -1,2,5,6- tetrahydropyridine -4- halogen;In the N- substitutions -4- piperidones, the upper substituents of N
Selected from Boc, Cbz, methyl, ethyl, isopropyl or benzyl;The aromatic ester of phosphorous acid three is selected from triphenyl phosphite, (the 4- second of phosphorous acid three
Base benzene) ester or phosphorous acid three (4- cumenes) ester;Organic base is selected from triethylamine or diisopropyl ethyl amine;
Second step, isopropylmagnesium chloride-lithium chloride adds to tetrahydrofuran or 2- methyltetrahydrofurans, -15 DEG C to 0 DEG C of temperature control,
N- is added dropwise and replaces -1,2,5,6- tetrahydropyridine -4- halogen, addition finishes stirring 1-2 hours, after exchange terminates, is subsequently added into alcoxyl
Ylboronic acid ester, then keeps 0 DEG C to 80 DEG C reaction;Cooling, adds 5-15% aqueous hydrochloric acid solutions and reaction is quenched, add ethyl acetate
Layering, organic layer saturated common salt washing after organic layer is evaporated, adds and N- substitutions -1,2,5,6- tetra- is obtained after mixed solvent mashing
Pyridinium hydroxide -4- borate sterlings, GC and nuclear-magnetism purity more than 98%, two step yields:55-63%;The alkoxy borate esters are selected from
Methoxyl group pinacol borate, isopropoxy pinacol borate, methoxy ylboronic acid DOPCP or isopropoxy boric acid are new
Pentadiol ester.
2. a kind of synthesis N- replaces the method for -1,2,5,6- tetrahydropyridine -4- borates, its feature according to claim 1
It is:In the first step, halogen is selected from bromine or iodine.
3. a kind of synthesis N- replaces the method for -1,2,5,6- tetrahydropyridine -4- borates, its feature according to claim 1
It is:In the first step, N- substitution -4- piperidones, the aromatic ester of phosphorous acid three, organic base and halogen equivalent proportion are 1:1-2.5:1-5:1-
2.5。
4. a kind of synthesis N- replaces the method for -1,2,5,6- tetrahydropyridine -4- borates, its feature according to claim 1
It is:In second step, N- replaces -1,2,5,6- tetrahydropyridine -4- halogen, isopropylmagnesium chloride-lithium chloride and alkoxy borate esters
Equivalent proportion is 1:1-1.5:1-2.
5. a kind of synthesis N- replaces the method for -1,2,5,6- tetrahydropyridine -4- borates, its feature according to claim 1
It is:In second step, mixed solvent is selected from normal heptane or n-hexane is mixed with ethanol according to different proportion respectively.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610014644.5A CN105566367B (en) | 2016-01-11 | 2016-01-11 | A kind of synthesis N replaces the method for the borate of 1,2,5,6 tetrahydropyridine 4 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610014644.5A CN105566367B (en) | 2016-01-11 | 2016-01-11 | A kind of synthesis N replaces the method for the borate of 1,2,5,6 tetrahydropyridine 4 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105566367A CN105566367A (en) | 2016-05-11 |
CN105566367B true CN105566367B (en) | 2017-10-13 |
Family
ID=55877056
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610014644.5A Active CN105566367B (en) | 2016-01-11 | 2016-01-11 | A kind of synthesis N replaces the method for the borate of 1,2,5,6 tetrahydropyridine 4 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105566367B (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107987097B (en) * | 2017-12-17 | 2019-11-29 | 沧州普瑞东方科技有限公司 | The synthesis technology of 2,6- dichloropyridine -4- boric acid pinacol ester |
CN109762007B (en) * | 2019-02-27 | 2021-05-11 | 大连联化化学有限公司 | Process method for synthesizing N-substituted-1, 2,5, 6-tetrahydropyridine-4-boric acid ester |
CN109970773A (en) * | 2019-04-03 | 2019-07-05 | 中昊(大连)化工研究设计院有限公司 | A kind of new synthetic method of N-Boc-1,2,5,6- tetrahydropyridine -4- pinacol borate |
CN110526936A (en) * | 2019-09-05 | 2019-12-03 | 中昊(大连)化工研究设计院有限公司 | A kind of new synthetic method of N- substitution -1,2,5,6- tetrahydropyridine -4- pinacol borate |
CN110563696B (en) * | 2019-09-30 | 2022-05-03 | 蚌埠产品质量监督检验研究院 | Process for preparing heteroatom-containing cyclohexene halide |
CN111004264B (en) * | 2019-12-28 | 2022-05-17 | 沧州普瑞东方科技有限公司 | Preparation method of N-substituted tetrahydropyridine-3/4-boric acid/ester |
CN111171063B (en) * | 2020-01-08 | 2022-06-14 | 大连双硼医药化工有限公司 | Process method for synthesizing N-substituted piperidine-4-boric acid |
CN113861230A (en) * | 2021-11-02 | 2021-12-31 | 河南应用技术职业学院 | Synthetic method of terbinafine intermediate |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102060867A (en) * | 2010-12-31 | 2011-05-18 | 大连联化医药技术有限公司 | Method for preparing potassium trifluoroborate series compounds |
CN102070586A (en) * | 2010-12-31 | 2011-05-25 | 大连联化医药技术有限公司 | Process method for synthesizing 4-site heteroatom-substituted cyclohexenyl halide |
CN102153579A (en) * | 2011-02-23 | 2011-08-17 | 兰州米诺生物科技有限公司 | Method for synthesizing N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester |
US20140256706A1 (en) * | 2013-03-11 | 2014-09-11 | The Regents Of The University Of Michigan | Bet bromodomain inhibitors and therapeutic methods using the same |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104788480B (en) * | 2015-01-09 | 2017-03-22 | 沧州普瑞东方科技有限公司 | A method of synthesizing aminophenylboronic acid pinacol ester |
-
2016
- 2016-01-11 CN CN201610014644.5A patent/CN105566367B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102060867A (en) * | 2010-12-31 | 2011-05-18 | 大连联化医药技术有限公司 | Method for preparing potassium trifluoroborate series compounds |
CN102070586A (en) * | 2010-12-31 | 2011-05-25 | 大连联化医药技术有限公司 | Process method for synthesizing 4-site heteroatom-substituted cyclohexenyl halide |
CN102153579A (en) * | 2011-02-23 | 2011-08-17 | 兰州米诺生物科技有限公司 | Method for synthesizing N-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester |
US20140256706A1 (en) * | 2013-03-11 | 2014-09-11 | The Regents Of The University Of Michigan | Bet bromodomain inhibitors and therapeutic methods using the same |
Also Published As
Publication number | Publication date |
---|---|
CN105566367A (en) | 2016-05-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105566367B (en) | A kind of synthesis N replaces the method for the borate of 1,2,5,6 tetrahydropyridine 4 | |
CN106810426B (en) | Method for synthesizing cannabidiol | |
CN102584795B (en) | Preparing method of crizotinib | |
CN104327119A (en) | Preparation method of tedizolid phosphate | |
CN105777710B (en) | A kind of Ai Le replaces the synthetic method of Buddhist nun | |
CN106365986A (en) | Compounds and preparation methods thereof, and uses of compounds in synthesis of brivaracetam | |
CN103642023B (en) | The synthetic method of a kind of unimodal molecular weight polyoxyethylene glycol and derivative thereof | |
CN105175340A (en) | Method for preparing high-purity dexmedetomidine hydrochloride crystal from high-purity intermediate crystal | |
CN112062712A (en) | Preparation method of 2- (5-bromo-3-methylpyridin-2-yl) acetic acid hydrochloride | |
CN106478747A (en) | The industrial manufacturing process of gemcitabine key intermediate sulfonation sugar | |
CN110669002B (en) | Synthetic method of 2-fluoro-3-hydroxypyridine-4-carboxylic acid | |
CN104910002B (en) | A kind of preparation method of dezocine key intermediate | |
CN105130887A (en) | Regorafenib preparation method | |
CN102180914A (en) | Preparation method of 2-deoxidizing-D-glucose | |
CN110407841A (en) | A kind of synthetic method of anti-tumor drug Rui Boxini | |
CN106916147A (en) | Compound and its production and use | |
CN104193643A (en) | Novel midbody for synthesizing anti-AIDS medicine reinforcing agent cobicistat | |
CN101891731A (en) | Method for synthesizing olopatatadine E-configurational isomer | |
CN103923135B (en) | A kind of deuterated 5-hydroxyl color D-glucosamine glycoside derivates and preparation method thereof | |
CN105968103A (en) | Synthesis method of anti-tumor medicine afatinib | |
CN108947908B (en) | New intermediate of brivaracetam with imidazole ring and synthesis method and application thereof | |
CN107778192A (en) | A kind of preparation method of N alcoxyls or benzyloxycarbonyl group chirality propylhomoserin | |
CN103570781B (en) | A kind of industrialized process for preparing of capecitabine | |
CN105440042B (en) | A kind of synthetic method of PP796 intermediates pyrimidine triazole | |
CN101805339A (en) | Entecavir compound prepared in novel method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |