CN105272905B - A kind of piperidine compounds and preparation method thereof - Google Patents
A kind of piperidine compounds and preparation method thereof Download PDFInfo
- Publication number
- CN105272905B CN105272905B CN201510719003.5A CN201510719003A CN105272905B CN 105272905 B CN105272905 B CN 105272905B CN 201510719003 A CN201510719003 A CN 201510719003A CN 105272905 B CN105272905 B CN 105272905B
- Authority
- CN
- China
- Prior art keywords
- compound
- piperidine
- preparation
- piperidine compounds
- obtains
- 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
- 150000003053 piperidines Chemical class 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- -1 hydroxypropyl Chemical group 0.000 claims abstract description 3
- 230000000977 initiatory effect Effects 0.000 claims abstract description 3
- 239000000463 material Substances 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N Benzylformate Chemical compound O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
- 229940125898 compound 5 Drugs 0.000 claims description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 5
- 229940125782 compound 2 Drugs 0.000 claims description 5
- 229940126214 compound 3 Drugs 0.000 claims description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 3
- JWIPGAFCGUDKEY-UHFFFAOYSA-L O[Cr](Cl)(=O)=O.C1=CC=NC=C1 Chemical compound O[Cr](Cl)(=O)=O.C1=CC=NC=C1 JWIPGAFCGUDKEY-UHFFFAOYSA-L 0.000 claims description 3
- 235000019257 ammonium acetate Nutrition 0.000 claims description 3
- 229910000085 borane Inorganic materials 0.000 claims description 3
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims description 2
- 239000005695 Ammonium acetate Substances 0.000 claims description 2
- 229940043376 ammonium acetate Drugs 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- DBMHTLOVZSDLFD-UHFFFAOYSA-N piperidin-1-ylmethanamine Chemical compound NCN1CCCCC1 DBMHTLOVZSDLFD-UHFFFAOYSA-N 0.000 claims description 2
- USISRUCGEISZIB-UHFFFAOYSA-N piperidin-3-one Chemical class O=C1CCCNC1 USISRUCGEISZIB-UHFFFAOYSA-N 0.000 claims description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims 1
- ZTRPYTHOEREHEN-UHFFFAOYSA-N piperazine pyridine Chemical compound N1CCNCC1.N1=CC=CC=C1.N1=CC=CC=C1 ZTRPYTHOEREHEN-UHFFFAOYSA-N 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 3
- 238000013459 approach Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000003304 gavage Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 150000005247 2-cyanopyrroles Chemical class 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical class ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- IWVVFOKZRXTWIN-UHFFFAOYSA-N tert-butyl 4-(1-amino-3-hydroxypropyl)piperidine-1-carboxylate Chemical class CC(C)(C)OC(=O)N1CCC(C(N)CCO)CC1 IWVVFOKZRXTWIN-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to a kind of piperidine compounds and preparation method thereof, the compound is N BOC 4 (hydroxypropyl of 1 amino 3) piperidines, using 4 piperidine carbinols as initiation material, reacted and synthesized by 6 steps, it is the important intermediate for preparing kinase inhibitor, is with a wide range of applications in the medicine for preparing prevention and treatment diabetes；Its preparation method raw material is cheap and easily-available, and synthetic method is simple, is a kind of completely new approach for synthesizing piperidine compounds, is adapted to the needs of scale industrial production.
Description
Technical field
The present invention relates to production of chemicals field, especially a kind of piperidine compounds and preparation method thereof.
Background technology
Piperidine compounds are the important intermediates for preparing kinase inhibitor, are the keys for preventing and treating diabetes medicament
Part (Preparat ion of 2-cyanopyrroles and their ana logues as DPP-IV
inhibi tors.PCT Int.Appl.(2004),WO 2004089362).Piperidine compounds are widely present in living with biology
In the drug molecule of property, there is application value in terms of diabetes are treated and prevented.Parent is done with the compound can further enter
Row synthesizes increasingly complex derivative, and condition is provided broadly to study such compound property.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of piperidine compounds.
Another technical problem to be solved by this invention is the preparation method for providing above-mentioned piperidine compounds.
In order to solve the above technical problems, the technical scheme is that：
A kind of piperidine compounds, N-BOC-4- (1- amino -3- hydroxypropyls) piperidines, its structural formula are that (I) is shown,
Preferably, above-mentioned piperidine compounds, the proton nmr spectra number of N-BOC-4- (1- amino -3- hydroxypropyls) piperidines
According to for 1.145-1.114 (m, 2H), 1.188-1.177 (m, 1H), 1.434 (s, 9H), 1.652-1.569 (q, 3H), 2.689-
2.636(m,6H),3.806(m,2H),4.151(b,2H)。
The preparation method of above-mentioned piperidine compounds, using 4- piperidine carbinols as initiation material, react synthesis targeted by 6 steps
Compound, comprise the following steps that：
(1) compound 14- piperidine carbinols progress Boc protects to obtain compound 2；
(2) compound 2 reduces the hydroxyl in 4- piperidine carbinols by pyridine chlorochromate (PCC) and obtains compound 3 into ketone；
(3) piperidones of compound 3 generates sour aminomethyl piperidine with malonic acid and ammonium acetate effect and obtains compound 4；
(4) compound 4 obtains compound 5 by borane reduction nipecotic acid into piperidine alcohols；
(5) progress separating-purifying obtains compound 6 after compound 5 protects amino by benzyl formate (Cbz)；
(6) compound 6 removes benzyl formate group by Pd/C and obtains target compound 7；Wherein,
Intermediate compound 5 in the preparation method of above-mentioned piperidine compounds, its structural formula are that (II) is shown,
Intermediate compound 6 in the preparation method of above-mentioned piperidine compounds, its structural formula are that (III) is shown,
The specific reaction equation of the preparation method of above-mentioned piperidine compounds is as follows：
The beneficial effects of the invention are as follows：
Above-mentioned piperidine compounds N-BOC-4- (1- amino -3- hydroxypropyls) piperidines be prepare kinase inhibitor it is important in
Mesosome, it is with a wide range of applications in the medicine for preparing prevention and treatment diabetes；Its preparation method raw material is cheap and easily-available,
Synthetic method is simple, is a kind of completely new approach for synthesizing piperidine compounds, is adapted to the needs of scale industrial production.
Brief description of the drawings
Fig. 1 is the HNMR spectrograms of N-BOC-4- (1- amino -3- hydroxypropyls) piperidines.
Embodiment
In order that those skilled in the art is better understood from technical scheme, with reference to embodiment
Technical scheme of the present invention is described in further detail.
Embodiment 1
The preparation method of N-BOC-4- (1- amino -3- hydroxypropyls) piperidines, is comprised the following steps that：
(1) triethylamine of 23g compounds 1 and 20g is dissolved in DCM (dichloromethane), added 43g (Boc)2O, room temperature
Lower reaction 14h；After reaction completely, system is washed three times with 0.5N hydrochloric acid solution 10ml, then with 20ml washings once, dries rotation
It is dry to obtain compound 2；TLC information：Raw material Rf=0.15, product Rf=0.6.Solvent：PE：EA=1：2.Product 40g is measured,
Colorless oil, yield 85%.
(2) 20.5g compounds 2 are dissolved in 400ml DCM, add 32.4g in batches at room temperature and cross pyridine chlorochromate
(PCC) 4h, is reacted at room temperature；Reaction is complete, and reaction solution is diluted with methyl tertiary butyl ether(MTBE) (400ml), suction filtered through kieselguhr, filtrate
It is spin-dried for.Diluted, filtered with the tertiary ether of first (200ml) again, filtrate is spin-dried for obtaining compound 3.TLC information：Raw material Rf=0.3, production
Product Rf=0.6.Solvent：PE：EA=3：1, obtain blackish green 11.5 grams of oily compounds 3 (crude product).
(3) 205g compounds 3,1223g malonic acid, 185g ammonium acetates are dissolved in 500ml ethanol, at 100 DEG C of heating
React 12h；Reaction is complete, system cooling, filters, filtration cakes torrefaction, obtains compound 4 (white solid) 105g, yield 39%.
(4) 92g compounds 4 are dissolved in 1354ml tetrahydrofurans (THF), 1354ml borine tetrahydrofurans are added dropwise in 0-10 degree
1h, 2h is reacted at room temperature, then be gradually heated to (70 DEG C) reaction 8h of backflow；Reaction is complete, and system is concentrated into 1/2,0-10 degree drop
Add 200ml methanol, be then heated to reflux 40min, system is spin-dried for, and 500ml water is added, with dichloromethane DCM and isopropanol i-
PrOH(3:1) mixed extractant solvent (5*500ml), after organic phase merges, drying is spin-dried for, and obtains the crude product 43.5g of compound 5, green
Oil.
(5) 43.5g compounds 5,35g potassium carbonate are added in 450g acetonitriles, 35g benzyl chloroformates (drop is added dropwise at room temperature
Add 10min), 14h is reacted at room temperature；After reaction completely, reaction solution concentration, pour into 1L water, with EA (ethyl acetate) (3*
500ml) extract, drying is spin-dried for；Cross post：PE：EA=1:1, obtain compound 6.TLC information：Product Rf=0.3.Solvent：PE：
EA=1：1, measure 41 grams of product, colorless oil, two step yields 45%.
(6) 82g compounds 6 are dissolved in 800ml methanol, added in 2L autoclaves, add 16g palladium carbons (Pd/C), led to
Hydrogen reacts 13h at room temperature in 1 MPa.System diatomite filters, and filtrate is spin-dried for obtaining finished product compound 7N-BOC-4- (1- ammonia
Base -3- hydroxypropyls) piperidines, measure 33 grams of product, colorless oil, yield 83%.As shown in figure 1, N-BOC-4- (1- amino -3-
Hydroxypropyl) piperidines HNMR spectrograms (CDCl3), its hydrogen modal data is：1.145-1.114 (m, 2H), 1.188-1.177 (m,
1H),1.434(s,9H),1.652-1.569(q,3H),2.689-2.636(m,6H),3.806(m,2H),4.151(b,2H)。
Above-mentioned specific reaction equation is as follows：
Application test example
Test mice is divided into two groups, and every group is placed into the cage for being provided with feed respectively, gives respectively by gavage
One group and second group of 0.5% methocel solution, one time a day, continuing 15, the next day after last is given starts to be administered,
Gavage gives the first group of gained compound N-BOC-4- of embodiment 1 (1- amino -3- hydroxypropyls) piperidinyl-1 0mg/kg, and gavage is given
Second group of glibenclamide 10mg/kg is given, is given by gavage；Then feed is removed from cage, and studies blood in each group
The change of sugar level, the results are shown in Table 1.
Table 1
The above-mentioned detailed description carried out with reference to embodiment to a kind of piperidine compounds and preparation method thereof, is to say
It is bright property rather than limited, several embodiments can be included according to limited scope, therefore it is of the invention total not departing from
Changing and modifications under body design, should belong within protection scope of the present invention.
Claims (1)
1. a kind of preparation method of piperidine compounds, the piperidine compounds are N-BOC-4- (1- amino -3- hydroxypropyls) piperazine
Pyridine, its structural formula are that (I) is shown,
It is characterized in that：
Using 4- piperidine carbinols as initiation material, synthesising target compound is reacted by 6 steps, is comprised the following steps that：
(1) the 4- piperidine carbinols of compound 1 progress Boc protects to obtain compound 2；
(2) compound 2 reduces the hydroxyl in 4- piperidine carbinols by pyridine chlorochromate and obtains compound 3 into ketone；
(3) piperidones of compound 3 generates sour aminomethyl piperidine with malonic acid and ammonium acetate effect and obtains compound 4；
(4) compound 4 obtains compound 5 by borane reduction nipecotic acid into piperidine alcohols；
(5) progress separating-purifying obtains compound 6 after compound 5 protects amino by benzyl formate；
(6) compound 6 removes benzyl formate group by Pd/C and obtains target compound 7；Wherein,
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510719003.5A CN105272905B (en) | 2015-10-29 | 2015-10-29 | A kind of piperidine compounds and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510719003.5A CN105272905B (en) | 2015-10-29 | 2015-10-29 | A kind of piperidine compounds and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105272905A CN105272905A (en) | 2016-01-27 |
| CN105272905B true CN105272905B (en) | 2017-12-19 |
Family
ID=55142805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510719003.5A Active CN105272905B (en) | 2015-10-29 | 2015-10-29 | A kind of piperidine compounds and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105272905B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004089362A1 (en) * | 2003-04-11 | 2004-10-21 | Novo Nordisk A/S | 2-cyanopyrroles and their analogues as ddp-iv inhibitors |
| JP2010037198A (en) * | 2006-11-22 | 2010-02-18 | Astellas Pharma Inc | Quinolone derivative or its pharmaceutically acceptable salt |
-
2015
- 2015-10-29 CN CN201510719003.5A patent/CN105272905B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| RN 1420857-49-3;ACS;《STN Registry》;20130214 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105272905A (en) | 2016-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105037061B (en) | A kind of utilize borinic acid, amine and the method for carbon dioxide synthesis of carbamates | |
| US9211333B2 (en) | Anti-cancer agents synthesized based on miliusane compounds | |
| CN103435538B (en) | (R) preparation method of-3-amido piperidine hydrochlorate | |
| CN104910158B (en) | 5,6,7,8-tetrahydropyrido[3,4-d] pyrimidine compound with bioactivity as well as preparation method and application thereof | |
| Averin et al. | Synthesis of a new family of adamantylpyridin-2-amines by palladium-catalyzed amination | |
| CN105949118B (en) | A kind of preparation method of 2- aryl quinoline derivatives | |
| CN105669652A (en) | Improved preparation method of bepotastine besilate | |
| CN105272905B (en) | A kind of piperidine compounds and preparation method thereof | |
| CN105732619A (en) | Synthesizing method of 5,6,7,8-tetrahydropyridino-[2,3-d]pyrimidine compound | |
| CN105017150B (en) | A kind of method of the outer amine of the amine asymmetric hydrogenation synthesis of chiral ring of palladium chtalyst quinoline 3 | |
| CN101812014A (en) | Amlodipine besylate compound and novel preparation method thereof | |
| CN110256342B (en) | Synthetic method of 2-cyano quinoline derivative | |
| CN107973745A (en) | Mono- deuterated derivatives of DNJ-C-6, synthetic method and purposes | |
| CN109553633B (en) | Preparation method of phenylacetic acid type aryne | |
| CN111848480A (en) | Method for synthesizing aryl difluoromethyl seleno ether from arylboronic acid and application thereof | |
| Forrat et al. | First catalytic enantioselective synthesis of the cocaine abuse therapeutic agent (S)-(+)-1-(4-{2-[bis (4-fluorophenyl) methoxy] ethyl} piperazin-1-yl)-2-phenyl-2-propanol | |
| CN105541713A (en) | Isoquinoline compound and synthetic method thereof | |
| CN104098547B (en) | A kind of process for purification of Fasudic hydrochloride | |
| CN104447528B (en) | The preparation method of pyridine-2,3-diethyl dicarboxylate | |
| CN103450141A (en) | Benzopyranone compound, as well as preparation method and application thereof | |
| CN106279112A (en) | A kind of Crizotinib intermediate and its preparation method and application | |
| CN104311473B (en) | A kind of piperidines and preparation method thereof | |
| CN104119381B (en) | A kind of preparation method of fotemustine | |
| CN108456172A (en) | A kind of chiral aza ring carbene precursor compound and its preparation method and application with benzimidazole skeleton | |
| CN112939855B (en) | Process for preparing 1, 4-dihydropyridine derivatives containing azulene ring structure |
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 | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 300457 A6-8 17, No. 80, Hai Yun street, Tianjin economic and Technological Development Zone, Tianjin Patentee after: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Address before: 300000 A6-8 17, No. 80, Hai Yun street, Binhai New Area, Tianjin. Patentee before: SPHINX SCIENTIFIC LABORATORY Corp. |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Piperidine compound and preparation method thereof Effective date of registration: 20190926 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2019120000007 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20200910 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) Co.,Ltd. Registration number: Y2019120000007 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A piperidine compound and its preparation method Effective date of registration: 20210526 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) Co.,Ltd. Registration number: Y2021120000020 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20220519 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2021120000020 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Piperidine compound and its preparation method Effective date of registration: 20220525 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2022120000023 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230612 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2022120000023 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A piperidine compound and its preparation method Effective date of registration: 20230703 Granted publication date: 20171219 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2023120000052 |