CN104119269A - Synthetic method of 6-isopropyl nicotinic acid - Google Patents
Synthetic method of 6-isopropyl nicotinic acid Download PDFInfo
- Publication number
- CN104119269A CN104119269A CN201310146525.1A CN201310146525A CN104119269A CN 104119269 A CN104119269 A CN 104119269A CN 201310146525 A CN201310146525 A CN 201310146525A CN 104119269 A CN104119269 A CN 104119269A
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- China
- Prior art keywords
- nicotinic acid
- acid
- limited
- sec
- synthetic method
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
Abstract
The invention discloses a novel synthetic method of 6-isopropyl nicotinic acid. Nicotinic acid as a starting material is subjected to a one-step Minisci reaction to obtain the 6-isopropyl nicotinic acid. The method has the advanategs of mild and simple reaction conditions, low cost, high yield and simple operation, and is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to a kind of new synthesis process of 6-sec.-propyl nicotinic acid, belong to medicine, chemical technology field.
Background technology
Nicotinic acid is also referred to as vitamin B3, or vitamin PP, is one of 13 kinds of VITAMIN of needed by human, is a kind of water-soluble vitamins, belongs to vitamin B complex.Nicotinic acid, for antipellagra, also can be used as blood expansion medicine, is used as in a large number the additive of food and feed; As medicine intermediate, can stop and the production of Vasonicit etc. for vazadrine, niacinamide, Buddhist nun.Its derivative is also widely used in biomedicine field, has good antiallergic activity (JMC1989,32 (3), 583-593; EP1852431).
The synthetic method of bibliographical information has as follows:
Route A (JACS1951,73,1368; WO2007/76034; WO2008/133753; JMC1989,32 (3), 583-593; EP1852431; BMCL2012,22 (6), 2212-2215; Zeitschrift fuer Naturforschung, B:Chemical Sciences, 2004,59 (10), 1121-1131).
Route B (US6350764)
Route C (WO2012/171337)
Route D (EJMC198924,517-530; JOC1999,64 (26), 9493-9498)
In route A, C, D, reaction yield is lower, reaction product complexity, and step is long.
In route B, raw material is not easy to obtain, and product purification difficulty is larger.
Comprehensively more above-mentioned four routes, reaction yield is lower, reaction product complexity, and step is long, also has raw material to be not easy to obtain, and product purification difficulty is large.
Summary of the invention
The present invention seeks to select a new synthetic route to prepare 6-sec.-propyl nicotinic acid, the method raw material is easy to get, inexpensive, and productive rate is high, and reaction conditions gentleness is suitable for a large amount of preparations.
Reaction scheme is as follows:
The new synthesis process of 6-sec.-propyl nicotinic acid of the present invention, in synthetic 6-sec.-propyl nicotinic acid (compound 3): Minisci reacts oxygenant used, including but not limited to ammonium persulphate, hydrogen peroxide, peroxy tert-butyl alcohol etc.; Catalyzer used, including but not limited to Silver Nitrate, ferrous sulfate etc.; Radical precursor used, including but not limited to isopropylformic acid, isopropyl iodide etc.; Acid used, including but not limited to sulfuric acid etc.; Reaction solvent is water, can be also DMSO, DMF, acetone etc.; Temperature of reaction is at 70-90 DEG C.
The present invention compared with prior art has following beneficial effect:
1, raw material nicotinic acid is cheap and easy to get, and productive rate is higher, and the reaction times is short.
2, reactions steps is short, only has single step reaction, has avoided loaded down with trivial details operation, has greatly improved working efficiency.
3, whole reaction scheme mild condition, is suitable for a large amount of preparations.
Embodiment
Embodiment 1: synthetic 6-sec.-propyl nicotinic acid (compound 3)
In the mixing solutions of nicotinic acid (1g, 8.1 mmoles) water-soluble (10 milliliters) and the vitriol oil (0.5 milliliter), under nitrogen protection, add isopropylformic acid (1.4g, 16.2 mmoles).Lucifuge adds Silver Nitrate (140mg, 0.1 mmole), ammonium persulphate (3.7g, 16.2 mmoles), is heated to 90 DEG C, stirs 3 hours.Be chilled to 0 DEG C, be neutralized to pH10, ethyl acetate extraction.Merge organic interdependent time and wash with saturated sodium bicarbonate solution and salt, anhydrous sodium sulfate drying.Concentrating under reduced pressure, residue ether recrystallization, vacuum-drying obtains compound (3) 0.88g, productive rate: 65.7%.
Claims (2)
1. the present invention discloses a kind of novel synthesis of 6-sec.-propyl nicotinic acid, Minisci occurs taking nicotinic acid as starting raw material and react a step and obtain target compound 6-sec.-propyl nicotinic acid.
2. the synthetic method of 6-sec.-propyl nicotinic acid as claimed in claim, is characterized in that: Minisci reacts oxygenant used, including but not limited to ammonium persulphate, hydrogen peroxide, peroxy tert-butyl alcohol etc.; Catalyzer used, including but not limited to Silver Nitrate, ferrous sulfate etc.; Radical precursor used, including but not limited to isopropylformic acid, isopropyl iodide etc.; Acid used, including but not limited to sulfuric acid etc.; Reaction solvent is water, can be also DMSO, DMF, acetone etc.; Temperature of reaction is at 70-90 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310146525.1A CN104119269A (en) | 2013-04-25 | 2013-04-25 | Synthetic method of 6-isopropyl nicotinic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310146525.1A CN104119269A (en) | 2013-04-25 | 2013-04-25 | Synthetic method of 6-isopropyl nicotinic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104119269A true CN104119269A (en) | 2014-10-29 |
Family
ID=51764935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310146525.1A Pending CN104119269A (en) | 2013-04-25 | 2013-04-25 | Synthetic method of 6-isopropyl nicotinic acid |
Country Status (1)
| Country | Link |
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| CN (1) | CN104119269A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658853A (en) * | 2018-05-03 | 2018-10-16 | 苏州大学 | A kind of 4- azepines aryl-triacontanol compound and its synthetic method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006053121A2 (en) * | 2004-11-10 | 2006-05-18 | Cgi Pharmaceuticals, Inc. | Imidazo[1 , 2-a] pyrazin-8-ylamines useful as modulators of kinase activity |
| WO2006138350A2 (en) * | 2005-06-15 | 2006-12-28 | Anormed Inc. | Chemokine receptor binding compounds |
| CN101223141A (en) * | 2005-03-10 | 2008-07-16 | Cgi药品股份有限公司 | Certain substituted amides, method of making, and method of use thereof |
| CN101309690A (en) * | 2005-08-16 | 2008-11-19 | 阿诺麦德股份有限公司 | Chemokine receptor binding compounds |
-
2013
- 2013-04-25 CN CN201310146525.1A patent/CN104119269A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006053121A2 (en) * | 2004-11-10 | 2006-05-18 | Cgi Pharmaceuticals, Inc. | Imidazo[1 , 2-a] pyrazin-8-ylamines useful as modulators of kinase activity |
| US20060178367A1 (en) * | 2004-11-10 | 2006-08-10 | Currie Kevin S | Certain imidazo[1,2-a]pyrazin-8-ylamines, method of making, and method of use thereof |
| CN101223141A (en) * | 2005-03-10 | 2008-07-16 | Cgi药品股份有限公司 | Certain substituted amides, method of making, and method of use thereof |
| WO2006138350A2 (en) * | 2005-06-15 | 2006-12-28 | Anormed Inc. | Chemokine receptor binding compounds |
| CN101309690A (en) * | 2005-08-16 | 2008-11-19 | 阿诺麦德股份有限公司 | Chemokine receptor binding compounds |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108658853A (en) * | 2018-05-03 | 2018-10-16 | 苏州大学 | A kind of 4- azepines aryl-triacontanol compound and its synthetic method |
| CN108658853B (en) * | 2018-05-03 | 2021-12-03 | 苏州大学 | 4-nitrogen heteroaryl alkanol compound and synthesis method thereof |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| DD01 | Delivery of document by public notice |
Addressee: Kejie-Bio (Suzhou) Pharmaceutical Co., Ltd. Document name: Notification of Publication and of Entering the Substantive Examination Stage of the Application for Invention |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20141029 |