CN110156750A - Pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag - Google Patents
Pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag Download PDFInfo
- Publication number
- CN110156750A CN110156750A CN201910392912.0A CN201910392912A CN110156750A CN 110156750 A CN110156750 A CN 110156750A CN 201910392912 A CN201910392912 A CN 201910392912A CN 110156750 A CN110156750 A CN 110156750A
- Authority
- CN
- China
- Prior art keywords
- flag
- methyl
- chloro
- pyrimidine
- lieting
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to a kind of pyrimidine rings14The preparation method of the amber love song Ge Lieting of C flag, include the following steps: by14The methylurea of C flag is dissolved in solvent, be added alkali, then be added dropwise malonate reaction, after be cooled to room temperature, obtained with acetic acid tune pH to 3~414The 1- methylbarbituric acid of C flag；It is added to the water again with phosphorus oxychloride and reacts to obtain solid and be14The chloro- 3- methyluracil of the 6- of C flag；In the mixed solvent is added with 2- cyano -5- fluorine bromobenzyl again, acid binding agent is then added and reacts142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) fluoro- benzonitrile white solid of -4- of C flag；(R) -3- amido piperidine hydrochlorate stirring and dissolving reacts finished product pyrimidine ring after adding alkali14The bent Ge Lieting of C flag；Finished product is reacted with succinic acid again14The amber love song Ge Lieting of C flag.The present invention, which has, is used for amber love song Ge Lieting pyrimidine ring14C flag,14C utilization rate height and advantage easy to operate.
Description
Technical field
The present invention relates to a kind of pyrimidine rings14The preparation method of the amber love song Ge Lieting of C flag, belongs to14C flag chemical combination
Object synthesis technical field.
Background technique
Radioactive isotope14It is (people, animal, plant, micro- in complex system that C flag organic matter is the corresponding non-marked object of research
Biology, soil, water body etc.) in movement, tracer necessary to changing rule.Carbon atom is the base to form organic compound scaffold
This element, using radioactive isotope14C flag organic matter is the most basic most common mark mode of organic matter；Relative to radiation
For property element tritium, stability is more preferable.
Radio isotope tracer technique is that Modern Chromatographic Analysis technology, Modern spectroscopy analytical technology and nuclear technology depth are melted
The civilian non-powered nuclear technology of conjunction and formation is early widely used to new drug (medicine, pesticide, veterinary drug etc.) exploitation, life external
The fields such as object science and environmental protection.
Because technology, funds, policy and talented people factor etc. restrict, it is very wide that China's radio isotope tracer technique, which uses not,
It is general.Especially in new medicine R&D process, domestic radioactive isotope14C raw material relies primarily on from the U.S., Russia, adds
It puts on airs, Britain, the ground import such as France.
Diabetes (Diabetes Mellitus, DM) are a kind of metabolic diseases of multi-pathogenesis, are exhausted due to insulin
Pair or relative deficiency cause blood glucose rise and cause organism metabolic disorder.Insulin-dependent diabetes mellitus can be divided into
(insulindependent diabetes mellitus, IDDM, i.e. type-1 diabetes mellitus) and Non-Insulin Dependent Diabetes Mellitus
(noninsulindependent diabetes mellitus, NIDDM, i.e. type-2 diabetes mellitus), wherein type-2 diabetes mellitus is the most
It is common, account for 90% of diabetic or more.
DPP IV (DPP-IV) is a kind of serine protease, it has expression in many tissues in vivo, such as
In T lymphocyte in intestines, liver, lung, kidney etc., and circulation.It is responsible for certain endogenous peptides in vivo, and (GLP-1 (7-36), pancreas are high
Blood glucose element) metabolic cleavage, and verified have the egg for fighting a variety of other peptides (GHRH, NPY, GLP-2, VIP) in vitro
White degrading activity, to promote the secretion of insulin to achieve the purpose that reduce blood glucose, to II type by reducing glucagon
Diabetes are highly effective.
Amber love song Ge Lieting is a kind of novel DPP-IV inhibitors, on March 26th, 2015, lists, is used in Japan
The treatment of long-term type-2 diabetes mellitus, medication is primary weekly, can effectively improve conditions of patients, adverse reaction is few but there is presently no with
In the preparation method of the amber love song Ge Lieting of drug labelling detection.
Summary of the invention
For disadvantage mentioned above, the purpose of the present invention is to provide a kind of pyrimidine rings14The system of the amber love song Ge Lieting of C flag
Preparation Method, can prepare the compound of the label detection for drug, and this method is suitable on amber love song Ge Lieting pyrimidine ring14C flag, this method14C utilization rate is high, and easy to operate.
Technical solution provided by the invention is as follows, a kind of pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag,
Include the following steps:
(1), will14The methylurea of C flag is dissolved in solvent, and alkali is added, malonate is then added dropwise, after being added dropwise 60~
80 DEG C back flow reaction 6~10 hours；It is cooled to room temperature, with acetic acid tune pH to 3~4, is stirred at room temperature after adding water after reaction
It is down to 0~5 DEG C of insulated and stirred crystallization, is filtered, drying obtains14The 1- methylbarbituric acid of C flag；Reaction equation is as follows:
Wherein solvent is methanol, ethyl alcohol or isopropanol, and alkali is sodium methoxide, sodium ethoxide, tert-butyl lithium or sodium hydroxide；
14The methylurea of C flag and the molar ratio of malonate are 1:1.15~1:1.25；
14The methylurea of C flag and the molar ratio of alkali are 1:6~1:10；
14The methylurea of C flag and the w/v (g:ml) of solvent are 1:30~1:60；
It (2), will be obtained in step (1)141- methylbarbituric acid and the phosphorus oxychloride of C flag are added to the water, at 65~80 DEG C
It chlorination reaction 1~3 hour, has reacted and has directly been spin-dried for, obtaining solid is14The chloro- 3- methyluracil crude product of the 6- of C flag；It will14C
The chloro- 3- methyluracil crude product sodium hydroxide solution of the 6- of label is dissolved at 50~60 DEG C, and hydrochloric acid solution tune pH to 6 is added dropwise,
White solid is precipitated, is cooled to 5~10 DEG C, heat preservation crystallization filters, and drying obtains white solid14The chloro- 3- methyl urine of the 6- of C flag
Pyrimidine；
Reaction equation is as follows:
Wherein14The 1- methylbarbituric acid of C flag and the w/v (g:ml) of phosphorus oxychloride are 1:50~1:80, are added
The weight of water be1420~35 times of the 1- methylbarbituric acid of C flag；
It (3), will be obtained in step (2)14The chloro- 3- methyluracil of the 6- of C flag is mixed with the addition of 2- cyano -5- fluorine bromobenzyl
In solvent, acid binding agent being then added and is reacted 1~3 hour at 55~70 DEG C, reaction terminates for reaction solution to be spin-dried for, add silica gel mixed sample,
Excessive 2- cyano -5- fluorine bromobenzyl is eluted with n-hexane again, the eluant, eluent containing product is spin-dried for, obtains14((6- is chloro- by the 2- of C flag
3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl) the fluoro- benzonitrile white solid of -4-；Its reaction equation is as follows:
14The molar ratio of the chloro- 3- methyluracil of the 6- of C flag and 2- cyano -5- fluorine bromobenzyl is 1:1.0~1:1.25；
14The w/v (g:ml) of the chloro- 3- methyluracil of the 6- of C flag and mixed solvent is 1:50~1:80；
14The molar ratio of the chloro- 3- methyluracil of the 6- of C flag and acid binding agent is 1:1.5~1:3；
Acid binding agent is n,N-diisopropylethylamine；Mixed solvent is ethyl acetate and N-Methyl pyrrolidone, ethyl acetate and N-
The volume ratio 1:1 of methyl pyrrolidone；
It (4), will be obtained in step (3)14((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- of 6- is phonetic by the 2- of C flag
Pyridine -1- methyl) the fluoro- benzonitrile of -4-, (R) -3- amido piperidine hydrochlorate, solvent and water mixing dissolution,
Add after alkali and reacted 6~10 hours at 60~80 DEG C, solution first clarify and white solid is precipitated afterwards, add isopropanol with
Unsaturated carbonate potassium solution continues insulation reaction 0.5~2 hour, and liquid separation while hot takes organic layer to be spin-dried for column chromatographic purifying finished product
Pyrimidine ring14The bent Ge Lieting of C flag；Its reaction equation is as follows:
Alkali is potassium carbonate, cesium carbonate, triethylamine or n,N-diisopropylethylamine, and solvent is isopropanol；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
(R) molar ratio of -3- amido piperidine hydrochlorate is 1:1.05~1:1.25；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
The molar ratio of alkali is 1:2~1:5；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
The w/v (g:ml) of water is 1:8~1:15；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
The w/v (g:ml) of solvent is 1:15~1:30；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
The w/v (g:ml) of isopropanol is 1:35~1:50；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
The w/v (g:ml) of unsaturated carbonate potassium solution is 1:35~1:50；
(5), by pyrimidine ring obtained in step (4)14The bent Ge Lieting of C flag solvent isopropanol dissolves, succinic acid solvent
Pyrimidine ring is added drop-wise in room temperature after isopropanol and water dissolution14In the bent Ge Lieting solution of C flag, white solid is precipitated, it is down to 5~
10 DEG C are continued stirring 0.5~2 hour, are filtered dry that white powdery solids are finished product14The amber love song Ge Lieting of C flag,
Its reaction equation is as follows:
Pyrimidine ring14The bent Ge Lieting of C flag and the molar ratio of succinic acid are 1:1.0~1:1.5,
Pyrimidine ring14The bent Ge Lieting of C flag and the w/v (g:ml) of isopropanol are 1:15~1:30；
The w/v (g:ml) of succinic acid and isopropanol is 1:45~1:65；
The w/v (g:ml) of succinic acid and water is 1:8~1:15.
The present invention compared with prior art possessed by advantage are as follows: the present invention be suitable for amber love song Ge Lieting pyrimidine ring
On14C flag can prepare the compound of the label detection for drug, this method14C utilization rate is high, is different from industrial production,
It is reacted suitable for milligram rank, and easy to operate.
Specific embodiment
Illustrate technical solution of the present invention below with reference to specific embodiment.
Embodiment
A kind of pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag, includes the following steps:
(1), will14Methyl urea (23mg, 0.3mmol), methanol 1ml, the sodium methoxide (130mg, 2.4mmol) of C flag are added
Dimethyl malenate (48mg, 0.36mmol) is slowly added dropwise in the stirring and dissolving into 10ml two mouth flask, is warming up to 70 DEG C, reflux
Reaction 8 hours, is cooled to room temperature, with acetic acid tune pH to 4, adds water 2ml, 1h is stirred at room temperature, be down to 5 DEG C of insulated and stirred 30min, takes out
Filter, is dried14The white solid 37mg of the 1- methylbarbituric acid of C flag, yield 85%；
It (2), will be obtained in step (1)14The 1- Methyl barbiturate (37mg, 0.25mmol) and phosphorus oxychloride of C flag
1ml water is added dropwise at room temperature after 2ml mixing, finishes, is warming up to 70 DEG C and reacts 2 hours, reacted and be directly spin-dried for, obtained solid
For14The chloro- 3- methyluracil crude product of the 6- of C flag；
It will1455 DEG C of the sodium hydroxide solution dissolutions of 1.5ml 5% of the 6- of C flag chloro- 3- methyluracil crude product, are added dropwise
White solid is precipitated in the hydrochloric acid solution tune pH to 6 of 3mol/L, is cooled to 10 DEG C, keeps the temperature 2h, filters, and drying obtains white solid14C
The chloro- 3- methyluracil 33mg of the 6- of label, yield 80%；
It (3), will be obtained in step (2)14The chloro- 3- methyluracil (33mg, 0.2mmol) of the 6- of C flag, 2- cyano-
5- fluorine bromobenzyl (47mg, 0.22mmol), 1ml N-Methyl pyrrolidone (NMP), 1ml ethyl acetate (DIPEA), stirring and dissolving,
It instills n,N-diisopropylethylamine (55mg, 0.42mmol), is warming up to 65 DEG C and reacts 2.5 hours, after reaction by reaction solution
Be spin-dried for, add silica gel mixed sample, first with pure hexane 50ml elute, ethyl acetate: the elution 100ml of n-hexane 1:5 100ml incited somebody to action
2- cyano -5- fluorine the bromobenzyl of amount washes out, then uses ethyl acetate instead: the eluant, eluent 150ml of n-hexane 1:1 will14The 2- ((6- of C flag
Chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl) the fluoro- benzonitrile elution of -4-, it is spin-dried for washing containing product
De- agent, obtains142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) fluoro- benzonitrile of -4- of C flag
White solid 49mg, yield 82%, purity 98.5%；
It (4), will be obtained in step (3)142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- of 6- of C flag
Pyrimidine -1- methyl) the fluoro- benzonitrile of -4- (49mg, 0.16mmol), (R) -3- amido piperidine hydrochlorate (32mg, 0.18mmol),
1ml isopropanol (IPA) and 0.5ml water stirring and dissolving, add potassium carbonate (80mg, 0.58mmol), are warming up to 70 DEG C of reactions 8
Hour, it adds 2ml isopropanol and 2ml unsaturated carbonate potassium solution continues insulation reaction 1 hour, liquid separation while hot takes organic layer to revolve
Dry chromatography is first eluted with n-hexane 100ml, then with ethyl acetate: product point is collected in n-hexane=1:5 elution, will be contained14C mark
The eluant, eluent of the bent Ge Lieting of note is spin-dried for, and obtains white solid14The bent Ge Lieting 50mg of C flag, yield 85%, purity 99.6%；
It (5), will be obtained in step (4)14The bent Ge Lieting (50mg, 0.14mmol) of C flag, with 1ml isopropanol
(IPA) it dissolves, succinic acid (18mg, 0.15mmol) is dissolved with 1ml isopropanol (IPA) and 0.2ml water, at room temperature by succinic acid
Solution instills14In the aqueous isopropanol of the bent Ge Lieting of C flag, white solid is precipitated, stirs 2 hours, is down to 10 DEG C and continues to stir
It mixes 1 hour, filters dry white powdery solids14The amber love song Ge Lieting 54mg of C flag, yield 81%, purity > 99%.
Claims (1)
1. a kind of pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag, includes the following steps:
(1), will14The methylurea of C flag is dissolved in solvent, and alkali is added, malonate is then added dropwise, 60~80 after being added dropwise
DEG C back flow reaction 6~10 hours；It is cooled to room temperature after reaction, with acetic acid tune pH to 3~4, drop is stirred at room temperature after adding water
It crystallizes, filters to 0~5 DEG C of insulated and stirred, drying obtains14The 1- methylbarbituric acid of C flag；
Wherein solvent is methanol, ethyl alcohol or isopropanol, and alkali is sodium methoxide, sodium ethoxide, tert-butyl lithium or sodium hydroxide；
14The methylurea of C flag and the molar ratio of malonate are 1:1.15~1:1.25；
14The methylurea of C flag and the molar ratio of alkali are 1:6~1:10；
14The methylurea of C flag and the w/v (g:ml) of solvent are 1:30~1:60；
It (2), will be obtained in step (1)141- methylbarbituric acid and the phosphorus oxychloride of C flag are added to the water, at 65~80 DEG C
It chlorination reaction 1~3 hour, has reacted and has directly been spin-dried for, obtaining solid is14The chloro- 3- methyluracil crude product of the 6- of C flag；It will14C
The chloro- 3- methyluracil crude product sodium hydroxide solution of the 6- of label is dissolved at 50~60 DEG C, and hydrochloric acid solution tune pH to 6 is added dropwise,
White solid is precipitated, is cooled to 5~10 DEG C, heat preservation crystallization filters, and drying obtains white solid14The chloro- 3- methyl urine of the 6- of C flag
Pyrimidine；
Wherein14The 1- methylbarbituric acid of C flag and the w/v (g:ml) of phosphorus oxychloride are 1:50~1:80, addition
The weight of water is1420~35 times of the 1- methylbarbituric acid of C flag；
It (3), will be obtained in step (2)14The chloro- 3- methyluracil of the 6- of C flag mixes molten with the addition of 2- cyano -5- fluorine bromobenzyl
In agent, acid binding agent being then added and is reacted 1~3 hour at 55~70 DEG C, reaction terminates for reaction solution to be spin-dried for, add silica gel mixed sample, then
Excessive 2- cyano -5- fluorine bromobenzyl is eluted with n-hexane, the eluant, eluent containing product is spin-dried for, obtains142- ((the chloro- 3- of 6- of C flag
Methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl) the fluoro- benzonitrile white solid of -4-；
14The molar ratio of the chloro- 3- methyluracil of the 6- of C flag and 2- cyano -5- fluorine bromobenzyl is 1:1.0~1:1.25；
14The w/v (g:ml) of the chloro- 3- methyluracil of the 6- of C flag and mixed solvent is 1:50~1:80；
14The molar ratio of the chloro- 3- methyluracil of the 6- of C flag and acid binding agent is 1:1.5~1:3；
Acid binding agent is n,N-diisopropylethylamine；Mixed solvent is ethyl acetate and N-Methyl pyrrolidone, ethyl acetate and N-
The volume ratio 1:1 of methyl pyrrolidone；
It (4), will be obtained in step (3)142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine-of 6- of C flag
1- methyl) the fluoro- benzonitrile of -4-, (R) -3- amido piperidine hydrochlorate, solvent and water mixing dissolution,
Add after alkali and reacted 6~10 hours at 60~80 DEG C, solution first clarify and white solid is precipitated afterwards, add isopropanol with
Unsaturated carbonate potassium solution continues insulation reaction 0.5~2 hour, and liquid separation while hot takes organic layer to be spin-dried for column chromatographic purifying finished product
Pyrimidine ring14The bent Ge Lieting of C flag；
Alkali is potassium carbonate, cesium carbonate, triethylamine or n,N-diisopropylethylamine, and solvent is isopropanol；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with
(R) molar ratio of -3- amido piperidine hydrochlorate is 1:1.05~1:1.25；
142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- and the alkali of C flag
Molar ratio be 1:2~1:5；
142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- and the water of C flag
W/v (g:ml) be 1:8~1:15；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with it is molten
The w/v (g:ml) of agent is 1:15~1:30；
14C flag 2- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- with it is different
The w/v (g:ml) of propyl alcohol is 1:35~1:50；
142- ((the chloro- 3- methyl -2,4- dioxo -3,4- dihydro -2H- pyrimidine -1- methyl of 6-) the fluoro- benzonitrile of -4- and full of C flag
W/v (g:ml) with solution of potassium carbonate is 1:35~1:50；
(5), by pyrimidine ring obtained in step (4)14The bent Ge Lieting of C flag solvent isopropanol dissolves, succinic acid solvent
Pyrimidine ring is added drop-wise in room temperature after isopropanol and water dissolution14In the bent Ge Lieting solution of C flag, white solid is precipitated, it is down to 5~
10 DEG C are continued stirring 0.5~2 hour, are filtered dry that white powdery solids are finished product14The amber love song Ge Lieting of C flag,
Pyrimidine ring14The bent Ge Lieting of C flag and the molar ratio of succinic acid are 1:1.0~1:1.5,
Pyrimidine ring14The bent Ge Lieting of C flag and the w/v (g:ml) of isopropanol are 1:15~1:30；
The w/v (g:ml) of succinic acid and isopropanol is 1:45~1:65；
The w/v (g:ml) of succinic acid and water is 1:8~1:15.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910392912.0A CN110156750A (en) | 2019-05-13 | 2019-05-13 | Pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910392912.0A CN110156750A (en) | 2019-05-13 | 2019-05-13 | Pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110156750A true CN110156750A (en) | 2019-08-23 |
Family
ID=67634283
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910392912.0A Pending CN110156750A (en) | 2019-05-13 | 2019-05-13 | Pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110156750A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101374523A (en) * | 2005-09-14 | 2009-02-25 | 武田药品工业株式会社 | Dipeptidyl peptidase inhibitors for treating diabetes |
| CN101573351A (en) * | 2006-11-29 | 2009-11-04 | 武田药品工业株式会社 | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| EP2682110A1 (en) * | 2011-03-03 | 2014-01-08 | Takeda Pharmaceutical Company Limited | Laminated tablet and manufacturing method therefor |
| CN105968093A (en) * | 2016-06-29 | 2016-09-28 | 郑州明泽医药科技有限公司 | Preparation method for trelagliptin succinate |
| CN106632241A (en) * | 2016-12-06 | 2017-05-10 | 安徽省金楠医疗科技有限公司 | Preparation method of trelagliptin succinate |
| CN108586360A (en) * | 2018-06-13 | 2018-09-28 | 峨眉山宏昇药业股份有限公司 | A kind of preparation method of the chloro- 3- methyluracils of 6- |
| CN108822080A (en) * | 2018-08-31 | 2018-11-16 | 四川新斯顿制药股份有限公司 | The preparation method of amber love song Ge Lieting |
| CN109331019A (en) * | 2018-09-20 | 2019-02-15 | 深圳前海九华国际供应链管理有限公司 | A kind of preparation method of compound amber love song Ge Lieting tablet |
-
2019
- 2019-05-13 CN CN201910392912.0A patent/CN110156750A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101374523A (en) * | 2005-09-14 | 2009-02-25 | 武田药品工业株式会社 | Dipeptidyl peptidase inhibitors for treating diabetes |
| CN101573351A (en) * | 2006-11-29 | 2009-11-04 | 武田药品工业株式会社 | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| EP2682110A1 (en) * | 2011-03-03 | 2014-01-08 | Takeda Pharmaceutical Company Limited | Laminated tablet and manufacturing method therefor |
| CN105968093A (en) * | 2016-06-29 | 2016-09-28 | 郑州明泽医药科技有限公司 | Preparation method for trelagliptin succinate |
| CN106632241A (en) * | 2016-12-06 | 2017-05-10 | 安徽省金楠医疗科技有限公司 | Preparation method of trelagliptin succinate |
| CN108586360A (en) * | 2018-06-13 | 2018-09-28 | 峨眉山宏昇药业股份有限公司 | A kind of preparation method of the chloro- 3- methyluracils of 6- |
| CN108822080A (en) * | 2018-08-31 | 2018-11-16 | 四川新斯顿制药股份有限公司 | The preparation method of amber love song Ge Lieting |
| CN109331019A (en) * | 2018-09-20 | 2019-02-15 | 深圳前海九华国际供应链管理有限公司 | A kind of preparation method of compound amber love song Ge Lieting tablet |
Non-Patent Citations (2)
| Title |
|---|
| SHENGHUI XU等: "Synthesis of Trelagliptin Succinate", 《ORGANIC PROCESS RESEARCH DEVELOPMENT》 * |
| 续佩君: "《高中物理概念和规律词典》", 30 June 2000, 辽宁教育出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bashary et al. | Design, and facile synthesis of 1, 3 diaryl-3-(arylamino) propan-1-one derivatives as the potential alpha-amylase inhibitors and antioxidants | |
| CN102584795B (en) | Preparing method of crizotinib | |
| CN109879733B (en) | Synthetic method of monofluoro bromoacetone derivative | |
| TW200813049A (en) | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases | |
| CN113234059B (en) | Preparation method of lipoic acid impurity A | |
| CN105017260A (en) | Preparation method of sitagliptin intermediate triazolopyrazine derivative | |
| US11767302B2 (en) | Reagents and methods for tetrazine synthesis | |
| CN105153004A (en) | Improved industrialization technology for preparing Vildagliptin | |
| CN102060782A (en) | Method for preparing chloropyrimidines or analogues thereof | |
| CN110156750A (en) | Pyrimidine ring14The preparation method of the amber love song Ge Lieting of C flag | |
| CN110627703A (en) | Difluoromethylation synthesis method of aromatic amine compound | |
| CN107743488A (en) | The base of the thriazaspiro of 2 oxo 1,3,8 [4.5] decane 3] formic acid derivates | |
| CN106749228B (en) | A kind of jamaicin drug and the preparation method and application thereof | |
| CN115974892A (en) | Triazole tetrazine compound and preparation method and application thereof | |
| CN106588749B (en) | Polysubstituted carbazole compound and its synthetic method and application | |
| CN114524748A (en) | New intermediate of roxasitah and new preparation method of roxasitah | |
| CN103333180A (en) | Preparation method of aspoxicillin | |
| CN105001197A (en) | Alogliptin derivative I, preparation method and application thereof | |
| CN105693606A (en) | Asymmetric synthesis method of optically pure (R)/(S)-hydroxychloroquine | |
| CN108003113B (en) | Synthetic method of medicine for treating diabetes | |
| CN101824004B (en) | Synthesization technique for ceftibuten side chain | |
| CN1328265C (en) | Method for preparing trifluoromethyl benzothiazole | |
| CN113072482B (en) | Preparation method of repaglinide deuterium-labeled metabolite | |
| CN103408520B (en) | 3-[(2-fluoro-6-methoxyl) phenyl]-5-tetrachlorophthalide, as well as preparation method thereof | |
| CN108912018A (en) | The preparation method and its usage of impurity compound in a kind of key intermediate for synthesizing Sulpiride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190823 |