CN106336399A - Preparation method of Topiroxostat process impurity - Google Patents
Preparation method of Topiroxostat process impurity Download PDFInfo
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- CN106336399A CN106336399A CN201510741721.2A CN201510741721A CN106336399A CN 106336399 A CN106336399 A CN 106336399A CN 201510741721 A CN201510741721 A CN 201510741721A CN 106336399 A CN106336399 A CN 106336399A
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- topiroxostat
- preparation
- process contaminants
- reaction
- alkali
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- 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
- C07D401/14—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 three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of Topiroxostat process impurity. The method is characterized in that Topiroxostat reacts with 2-cyanoisoniazide in the presence of an alkali to obtain the Topiroxostat process impurity. The preparation method has the advantages of commercial reagents and raw materials, short reaction time, simplicity in operation and post-treatment, high purity of the above obtained product, and suitableness for industrial production.
Description
Technical field
The present invention relates to the preparation method of Topiroxostat process contaminants.
Background technology
Gout is a kind of common disease leading to uric acid to generate exception because of purine metabolic disturbance, is classified as 21 century 20 by the United Nations
One of big chronic disease, is the second largest metabolism class disease being only second to diabetes." hyperuricemia and gout treatment China Consensus of experts "
Point out, the popular of hyperuricemia (hyperuricemia, hua) totally assumes the trend raising year by year, the ill people of hua
Group assumes the trend of increasingly rejuvenation, and increases with age.
The gout causing currently for hyperuricemia and hyperuricemia, respectively according to the period (premonition of premonition gout outbreak
Phase), gout stage of attack and gout paracmasis carry out corresponding living environment adjustment and various drug therapy.Premonition just adjusted during the phase
Everyday environments are simultaneously aided with colchicin and are prevented, and during stage of attack with drug therapy such as steroid and nonsteroidal anti-inflammatory agents are just
Centered on treated, outbreak alleviate after just instruct patient improvement habits and customs, when improve incomplete when be clearly uric acid row
Let out after low type or uric acid produce hyperfunction type, give probenecid, BBR is such has uric acid excretion effect, benzene
Sulphur oxazolone is such to have suppression uric acid resorption, citrate is such improves aciduria effect, xanthine oxidase
Such medicine that inhibitor allopurinol etc. has suppression uric acid generation effect is treated.If in premorbid 2-3
Hour has just taken colchicin, then it just can suppress chemotaxis and the phagocytosis of neutrophil cell etc., thus can
To prevent 90% morbidity.But this medicine will control in bottom line, judge period of disease when having multiple side effects, using
Carry out taking also highly difficult.
Although based on drug therapy, the medicine that can be used for the uric acid hyperfunction type of generation but only has allopurinol, and its metabolism
Product alloxanthine is likely to accumulate in internal formation calculus.And it was further reported this medicine can cause eruption, renal function
Lowly, the side effect such as hepatitis.
Topiroxostat (topiroxostat), is a kind of new xanthine oxidase inhibitor, and in August, 2013 lists in Japan,
It can also slightly suppress the activity of cytochrome c yp3a4 hypotype in addition to the activity of suppression xanthine oxidase, is expected to become
The newtype drug for the treatment of gout.
It is below the structure of Topiroxostat process contaminants:
Content of the invention
For above-mentioned technical problem, the purpose of the present invention is: provides a kind of preparation method of Topiroxostat process contaminants.
The technical solution of the present invention is achieved in that the preparation method of Topiroxostat process contaminants, comprises the steps of
Topiroxostat and 2- cyano group isoniazid, in the presence of alkali, reaction obtains Topiroxostat process contaminants；
Preferably, reaction temperature is 0～100 DEG C.
Preferably, reaction dissolvent is toluene, oxolane, dioxane, methyl alcohol, ethanol, propyl alcohol, isopropanol, the tert-butyl alcohol
In one or more.
Preferably, alkali used by reaction be sodium methoxide, caustic alcohol, potassium methoxide, potassium ethoxide, sodium tert-butoxide, a kind of in potassium tert-butoxide
Or it is several.
Preferably, Topiroxostat in step (1), 2- cyano group isoniazid, the mol ratio of alkali be 1:1.0:1.0 to 1.0～2.0～
3.0.
Due to the utilization of technique scheme, the present invention compared with prior art has the advantage that
The preparation method of Topiroxostat process contaminants of the present invention, reagent used and raw material are all commercially available, and the time of reaction is shorter,
Operation and post processing are simple；Prepared product purity is high, suitable industrialized production.
Specific embodiment
Further illustrate the present invention with embodiment below, but the present invention is not intended to be limited thereto.
Embodiment 1: the preparation of Topiroxostat process contaminants
Take Topiroxostat 24.8g (0.1mol), methyl alcohol 300ml, sodium methoxide 57g (0.15mol) respectively, insert 1000ml tri-
In mouth flask, stirring, add 2- cyano group isoniazid 16.2g (0.1mol), react 3h, tlc detects extent of reaction, show
Reaction finishes.Evaporate solvent, add 200ml water, 100ml × 3 dichloromethane extraction point liquid.Combined dichloromethane phase, no
Water magnesium sulfate is dried, and filters off drier, and organic phase is concentrated to give yellow solid, and chloroform/n-hexane (1:2) mixed solvent recrystallizes
Obtain yellow solid, i.e. Topiroxostat process contaminants 28.7g.Yield: 73.2%.
Ms (+1): 393.
1h-nmr (dmso-d6) δ ppm:7.56～7.57 (1h, d), 7.61～7.62 (2h, d), 7.82 (1h, s), 8.15 (1h,
D), 8.48 (1h, d), 8., 65～8.66 (2h, d), 8.71 (1h, d), 9.04 (1h, d), 14.85 (1h, s), 14.92 (1h,
s).
Above-described embodiment only technology design to illustrate the invention and feature, its object is to allow person skilled in the art
Will appreciate that present disclosure and be carried out, can not be limited the scope of the invention with this, all smart according to the present invention
Equivalence changes or modification that god's essence is made, all should cover in protection scope of the present invention.
Claims (5)
1. the preparation method of Topiroxostat process contaminants, comprises the steps of
Topiroxostat and 2- cyano group isoniazid, in the presence of alkali, reaction obtains Topiroxostat process contaminants；
2. Topiroxostat process contaminants according to claim 1 preparation method it is characterised in that: reaction temperature be 0～
100℃.
3. Topiroxostat process contaminants according to claim 1 preparation method it is characterised in that: reaction dissolvent be first
In benzene, oxolane, dioxane, methyl alcohol, ethanol, propyl alcohol, isopropanol, the tert-butyl alcohol one or more.
4. according to claim 1, the preparation method of Topiroxostat process contaminants it is characterised in that: alkali used by reaction
For in sodium methoxide, caustic alcohol, potassium methoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide one or more.
5. Topiroxostat process contaminants according to claim 1 preparation method it is characterised in that: in step (1)
Topiroxostat, 2- cyano group isoniazid, the mol ratio of alkali are 1:1.0:1.0 to 1.0～2.0～3.0.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510741721.2A CN106336399A (en) | 2015-11-03 | 2015-11-03 | Preparation method of Topiroxostat process impurity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510741721.2A CN106336399A (en) | 2015-11-03 | 2015-11-03 | Preparation method of Topiroxostat process impurity |
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| CN106336399A true CN106336399A (en) | 2017-01-18 |
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| CN201510741721.2A Pending CN106336399A (en) | 2015-11-03 | 2015-11-03 | Preparation method of Topiroxostat process impurity |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108017619A (en) * | 2017-12-06 | 2018-05-11 | 成都惟邦药业有限公司 | A kind of Topiroxostat impurity and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1561340A (en) * | 2002-01-28 | 2005-01-05 | 株式会社富士药品 | Novel 1,2,4-triazole compound |
| CN103724329A (en) * | 2013-12-23 | 2014-04-16 | 济南百诺医药科技开发有限公司 | Preparation method of 4-[5-(pyridyl-4-yl)-1H-[1,2,4]triazolyl-3-yl]pyridyl-2-formonitrile |
| CN104151297A (en) * | 2014-08-27 | 2014-11-19 | 庄妍 | Preparation of 4-[5-(pyridine-4-yl)-1H-[1,2,4]triazole-3-yl]pyridine-2-formonitrile |
-
2015
- 2015-11-03 CN CN201510741721.2A patent/CN106336399A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1561340A (en) * | 2002-01-28 | 2005-01-05 | 株式会社富士药品 | Novel 1,2,4-triazole compound |
| CN103724329A (en) * | 2013-12-23 | 2014-04-16 | 济南百诺医药科技开发有限公司 | Preparation method of 4-[5-(pyridyl-4-yl)-1H-[1,2,4]triazolyl-3-yl]pyridyl-2-formonitrile |
| CN104151297A (en) * | 2014-08-27 | 2014-11-19 | 庄妍 | Preparation of 4-[5-(pyridine-4-yl)-1H-[1,2,4]triazole-3-yl]pyridine-2-formonitrile |
Non-Patent Citations (1)
| Title |
|---|
| TAKAHIRO SATO ET AL.: "Discovery of 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole,FYX-051-a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108017619A (en) * | 2017-12-06 | 2018-05-11 | 成都惟邦药业有限公司 | A kind of Topiroxostat impurity and preparation method thereof |
| CN108017619B (en) * | 2017-12-06 | 2020-08-11 | 成都惟邦药业有限公司 | Topiroxostat impurity and preparation method thereof |
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Application publication date: 20170118 |