CN104098562A - Synthetic method of 5,6-dihydropyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione - Google Patents
Synthetic method of 5,6-dihydropyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione Download PDFInfo
- Publication number
- CN104098562A CN104098562A CN201310125810.5A CN201310125810A CN104098562A CN 104098562 A CN104098562 A CN 104098562A CN 201310125810 A CN201310125810 A CN 201310125810A CN 104098562 A CN104098562 A CN 104098562A
- Authority
- CN
- China
- Prior art keywords
- pyrimidine
- diketone
- sodium
- synthetic method
- dihydro
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses an important intermediate 5,6-dihydro-2-mercaptopyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione obtained through one pot process by using easily available raw materials comprising methyl acrylate, ethyl cyanoacetate and thiourea. The intermediate is reduced by Raney-Ni to obtain 5,6-dihydro-2-mercaptopyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione. A synthetic method of 5,6-dihydro-2-mercaptopyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione has the advantages of low cost, mild reaction conditions, simple operation and easy mass preparation.
Description
Technical field
The present invention relates to a kind of 5,6-dihydropyridine [2,3-d] pyrimidine-4, the synthesis technique of 7 (3H, 8H)-diketone, belongs to medicine, chemical technology field.
Background technology
As important natural product pyrimidine base (uridylic, thymus pyrimidine and cytosine(Cyt)), they have formed nucleic acid.Pyrimidine and derivative thereof are the important intermediate of forming a connecting link between chemical industry and medicinal industry, are widely used in the fields such as medicine, agricultural chemicals.
In pyrimidine derivatives, some compound has good antitumor action, has good antiviral activity; Also some compound has anti-inflammatory, analgesia and the biological activity such as antibacterial.
Summary of the invention
The present invention seeks to select a new synthetic route to prepare 5,6-dihydropyridine [2,3-d] pyrimidine-4,7 (3H, 8H)-diketone, this route raw material is easy to get, inexpensive, and productive rate is high, reaction conditions is gentle, is suitable for industrial production, has extremely strong economic implications.
Reaction scheme is as follows:
Of the present invention 5,6-dihydropyridine [2,3-d] pyrimidine-4, the synthetic method of 7 (3H, 8H)-diketone, synthetic 5,6-dihydro-2-mercaptopyridine [2,3-d] pyrimidine-4,7 (3H, in 8H)-diketone (compound 4): methyl acrylate, ethyl cyanoacetate and thiocarbamide one kettle way obtain important intermediate sodium alkoxide used, including but not limited to sodium methylate, sodium ethylate, sodium isopropylate and sodium tert-butoxide etc.; Reaction solvent can be anhydrous methanol, can be also dehydrated alcohol, Virahol and the trimethyl carbinol etc.; Temperature of reaction is at 65 to 100 ℃.
Of the present invention 5,6-dihydropyridine [2,3-d] pyrimidine-4, the synthetic method of 7 (3H, 8H)-diketone, in synthetic 5,6-dihydropyridine [2,3-d] pyrimidine-4, in 7 (3H, 8H)-diketone (compound 5): temperature of reaction is at 100 to 105 ℃.
Embodiment
Embodiment 1: synthetic 5,6-dihydro-2-mercaptopyridine [2,3-d] pyrimidine-4,7 (3H, 8H)-diketone (compound 4)
In reaction flask, add methyl acrylate (1) (34.5g, 0.4 mole), ethyl cyanoacetate (2) (45.3g, 0.4 mole), thiocarbamide (3) (30.5g, 0.4 mole), sodium methylate (71.4g, 1.32 moles) and methyl alcohol (1.7 liters), stir reflux 40 hours.Be cooled to room temperature, suction filtration, gained solid recrystallizing methanol, obtains white solid (4) 32.4g, yield: 40.5%.
Embodiment 2: synthetic 5,6-dihydropyridine [2,3-d] pyrimidine-4,7 (3H, 8H)-diketone (compound 5)
Raney-Ni (65g) carefully joins 5,6-dihydro-2-mercaptopyridine [2,3-d] pyrimidine-4 in batches, in the suspension of 7 (3H, 8H)-diketone (32.4g, 0.16 mole) and water (25 milliliters), and reflux 3 hours.Be cooled to room temperature, suction filtration, filtrate concentrates to obtain white solid (5) 29.2g, yield: 85%.
Claims (3)
1. the present invention discloses a kind of 5,6-dihydropyridine [2,3-d] pyrimidine-4, the synthetic method of 7 (3H, 8H)-diketone, comprises following steps: (1) methyl acrylate, ethyl cyanoacetate and thiocarbamide one kettle way under the effect of sodium alkoxide obtains important intermediate 5,6-dihydro-2-mercaptopyridine [2,3-d] pyrimidine-4,7 (3H, 8H)-diketone; (2) 5,6-dihydro-2-mercaptopyridine [2,3-d] pyrimidine-4,7 (3H, 8H)-diketone obtains target compound through Raney-Ni reduction.
2. as claimed in claim 5,6-dihydropyridine [2,3-d] pyrimidine-4,7 (3H, the synthetic method the first step of 8H)-diketone, it is characterized in that: methyl acrylate, ethyl cyanoacetate and thiocarbamide one kettle way obtain important intermediate sodium alkoxide used, including but not limited to sodium methylate, sodium ethylate, sodium isopropylate and sodium tert-butoxide etc.; Reaction solvent can be anhydrous methanol, can be also dehydrated alcohol, Virahol and the trimethyl carbinol etc.; Temperature of reaction is at 65 to 100 ℃.
3. as claimed in claim 5,6-dihydropyridine [2,3-d] pyrimidine-4, the synthetic method second step of 7 (3H, 8H)-diketone, is characterized in that: the first step gained intermediate obtains target compound through Raney-Ni reduction, and temperature of reaction is at 100 to 105 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310125810.5A CN104098562A (en) | 2013-04-12 | 2013-04-12 | Synthetic method of 5,6-dihydropyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310125810.5A CN104098562A (en) | 2013-04-12 | 2013-04-12 | Synthetic method of 5,6-dihydropyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104098562A true CN104098562A (en) | 2014-10-15 |
Family
ID=51667146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310125810.5A Pending CN104098562A (en) | 2013-04-12 | 2013-04-12 | Synthetic method of 5,6-dihydropyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104098562A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002006245A1 (en) * | 2000-07-05 | 2002-01-24 | Synaptic Pharmarceutical Corporation | Selective melanin concentrating hormone-1 (mch1) receptor antagonists and uses thereof |
| US6720324B2 (en) * | 2000-07-05 | 2004-04-13 | Synaptic Pharmaceutical Corporation | Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof |
-
2013
- 2013-04-12 CN CN201310125810.5A patent/CN104098562A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002006245A1 (en) * | 2000-07-05 | 2002-01-24 | Synaptic Pharmarceutical Corporation | Selective melanin concentrating hormone-1 (mch1) receptor antagonists and uses thereof |
| US6720324B2 (en) * | 2000-07-05 | 2004-04-13 | Synaptic Pharmaceutical Corporation | Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| 任青云等: "《吡啶并嘧啶类化合物的合成研究进展》", 《有机化学》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106608876B (en) | A kind of preparation method of high-purity Pa Boxini | |
| CN103261173A (en) | Method for preparation of 2-ethyl-4-amtno-5-cyanopyrimidine | |
| CN103113300A (en) | Preparation method and application of compound with antitumor activity | |
| CN103172639B (en) | A kind of preparation method of the hexa-atomic two ring guanidines based on Guanidinium hydrochloride | |
| CN104098562A (en) | Synthetic method of 5,6-dihydropyrimidine[2,3-d]pyrimidine-4,7(3H,8H)-dione | |
| CN104341345B (en) | A kind of synthetic method of 2-methoxyl group-6-ketone-5,6,7,8-tetrahydroquinoline | |
| CN103992278B (en) | A kind of synthetic method of cytosine | |
| CN104109182A (en) | Preparation method of gemcitabine hydrochloride | |
| CN101555248B (en) | Method for preparing poly-substituted 1, 5-naphthyridine compound | |
| CN103896859A (en) | Process for synthesizing cytosine | |
| CN104496913B (en) | A method of preparing 5- substitution -2,4- dimethyl sulphur-based pyrimidines | |
| CN110156672B (en) | Preparation method of semicarbazide compound and application of prepared compound | |
| CN106397416B (en) | A kind of preparation method of Tegafur | |
| CN104211644B (en) | A kind of synthetic method of 3,4-dichloro-pyridazine | |
| CN101935317B (en) | Synthesizing method of 2-methyl-7-(substituted pyrimidine-4-amino)-4-(substituted piperazine-1-base) piperidine-1-base) isoindoline-1-ketone and intermediate thereof | |
| CN105175400A (en) | Preparation method of Afatinib intermediate | |
| CN106883185B (en) | Preparation method of 4-chloro-2-trifluoromethylpyrimidine | |
| CN105461603A (en) | Preparation method of fudosteine | |
| CN104478762B (en) | Preparation method of N,O-dimethyl-N-nitroisourea | |
| CN102399196A (en) | Synthesizing method of 4,6-dihydroxy-2-methylpyrimidine | |
| CN103242244B (en) | Canertinib preparation method | |
| CN1800169B (en) | Pemetrexed disodium key intermediate and its synthesis method, and method for synthesizing pemetrexed disodium from the said intermediate | |
| CN101555225B (en) | Method for preparing poly-substituted quinoline compound | |
| CN105218554A (en) | The synthesis technique of 4-chlorine pyrrolo-[2,3-D] pyrimidine | |
| CN103304527A (en) | Novel preparation method of 5-nitrobenzofuran-2-formic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20141015 |