DE1264445B - Process for the preparation of 2,6-dichloro-5-fluoropyrimidine - Google Patents
Process for the preparation of 2,6-dichloro-5-fluoropyrimidineInfo
- Publication number
- DE1264445B DE1264445B DER36298A DER0036298A DE1264445B DE 1264445 B DE1264445 B DE 1264445B DE R36298 A DER36298 A DE R36298A DE R0036298 A DER0036298 A DE R0036298A DE 1264445 B DE1264445 B DE 1264445B
- Authority
- DE
- Germany
- Prior art keywords
- fluoropyrimidine
- dichloro
- fluorouracil
- preparation
- ethyl
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Verfahren zur Herstellung von 2, 6-Dichlor-5-fluorpyrimidin Die Erfindung betrifft ein Verfahren zur Herstellung von 2,6-Dichlor-5-fluorpyrimidin. Gemäß der Erfindung wird diese Verbindung hergestellt, indem man ein l-Alkyl-5-fluoruracil in Gegenwart von Phosphorsäure bzw. geringen Mengen Wasser mit Phosphoroxychlorid bei Rückflußtemperatur umsetzt.Process for the preparation of 2,6-dichloro-5-fluoropyrimidine The invention relates to a process for the preparation of 2,6-dichloro-5-fluoropyrimidine. According to the Invention this compound is prepared by adding a l-alkyl-5-fluorouracil in the presence of phosphoric acid or small amounts of water with phosphorus oxychloride converts at reflux temperature.
An diesem Verfahren ist überraschend, daß es in einer Stufe gelingt, das Ausgangsprodukt gleichzeitig zu entalkylieren und zu halogenieren. Ein solcher Reaktionsablauf war bei derartigen Heterocyclen bisher nicht bekannt. What is surprising about this process is that it succeeds in one step to dealkylate and halogenate the starting product at the same time. Such a The course of the reaction in such heterocycles was not previously known.
Die nach dem Verfahren der Erfindung hergestellte Verbindung ist ein wichtiges Zwischenprodukt für die Herstellung von cytostatisch wirksamen Antimetaboliten, beispielsweise 5-Fluoruracil und 5-Fluorcytosin. The compound made by the method of the invention is an important intermediate for the production of cytostatic antimetabolites, for example 5-fluorouracil and 5-fluorocytosine.
Das 2,6-Dichlor-5-fluorpyrimidin wurde bisher in 84,50/0iger Ausbeute hergestellt aus 5-Fluoruracil, das wiederum aus 5-Äthylisothioharnstoff und dem Kaliumsalz von ol-Fluor-P-hydroxyacrylsäureäthylester über das 2-Äthylmercapto-5-fluor-6-hydroxypyrimidin in nur 17,28°/Oiger Ausbeute, bezogen auf das Harnstoffderivat, erhältlich ist. Das gemäß der Erfindung als Ausgangsstoff verwendbare l-Äthyl-5-fluoruracil ist hingegen erhältlich aus N-Äthylharnstoff und Fluormalonsäurediäthylester über 1 -Äthyl-5-fiuor-barbitursäure und dann l-Äthyl-4-chlor-5-fluoruracil in 640/0der Ausbeute, bezogen auf das Harnstoffderivat. The 2,6-dichloro-5-fluoropyrimidine has so far been in 84.50/0 yield made from 5-fluorouracil, which in turn is made from 5-ethylisothiourea and the Potassium salt of ethyl ol-fluoro-P-hydroxyacrylate via 2-ethylmercapto-5-fluoro-6-hydroxypyrimidine is available in only 17.28% yield, based on the urea derivative. The usable according to the invention as a starting material is l-ethyl-5-fluorouracil on the other hand, available from N-ethylurea and fluoromalonic acid diethyl ester via 1 -Ethyl-5-fluorobarbituric acid and then l-ethyl-4-chloro-5-fluorouracil in 640/0der Yield based on the urea derivative.
Beispiel 600 mg 1-Äthyl-5-fluoruracil (F.:131"C) werden mit zwei Tropfen Wasser und 5 mol Phosphoroxychlorid 8 Stunden unter Rückfluß erhitzt. Das überschüssige Phosphoroxychlorid wird dann im Vakuum abdestilliert und der Rückstand mit Eis-Äther-Gemisch zersetzt. Die Ätherschicht wird mit Natriumsulfat entwässert und abfiltriert. Der Äther wird abdestilliert und der Rückstand im Vakuum fraktioniert. Example 600 mg of 1-ethyl-5-fluorouracil (F.:131 "C) are mixed with two Drops of water and 5 mol of phosphorus oxychloride heated under reflux for 8 hours. That Excess phosphorus oxychloride is then distilled off in vacuo and the residue decomposed with a mixture of ice and ether. The ether layer is dehydrated with sodium sulfate and filtered off. The ether is distilled off and the residue is fractionated in vacuo.
2,6-Dichlor-5-fluorpyrimidin geht im Vakuum von 16 Torr bei 75 bis 80"C über. 2,6-dichloro-5-fluoropyrimidine goes in a vacuum of 16 torr at 75 to 80 "C about.
Ausbeute: 570 mg; F.: 38° C. Yield: 570 mg; F .: 38 ° C.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DER36298A DE1264445B (en) | 1963-10-09 | 1963-10-09 | Process for the preparation of 2,6-dichloro-5-fluoropyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DER36298A DE1264445B (en) | 1963-10-09 | 1963-10-09 | Process for the preparation of 2,6-dichloro-5-fluoropyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1264445B true DE1264445B (en) | 1968-03-28 |
Family
ID=7404869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DER36298A Pending DE1264445B (en) | 1963-10-09 | 1963-10-09 | Process for the preparation of 2,6-dichloro-5-fluoropyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1264445B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB877318A (en) * | 1959-06-03 | 1961-09-13 | Hoffmanni La Roche & Co Ag F | The manufacture of cytidines |
-
1963
- 1963-10-09 DE DER36298A patent/DE1264445B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB877318A (en) * | 1959-06-03 | 1961-09-13 | Hoffmanni La Roche & Co Ag F | The manufacture of cytidines |
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