CH314006A - Process for the preparation of a pyrimidine derivative - Google Patents
Process for the preparation of a pyrimidine derivativeInfo
- Publication number
- CH314006A CH314006A CH314006DA CH314006A CH 314006 A CH314006 A CH 314006A CH 314006D A CH314006D A CH 314006DA CH 314006 A CH314006 A CH 314006A
- Authority
- CH
- Switzerland
- Prior art keywords
- chlorophenyl
- amino
- preparation
- hydroxy
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 7
- 238000002360 preparation method Methods 0.000 title description 4
- 150000003230 pyrimidines Chemical class 0.000 title description 2
- KTEOTBKBKDEYDF-UHFFFAOYSA-N 2-amino-5-(4-chlorophenyl)-6-ethyl-1h-pyrimidin-4-one Chemical compound N1C(N)=NC(=O)C(C=2C=CC(Cl)=CC=2)=C1CC KTEOTBKBKDEYDF-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 3
- TUBVXYXSEWNSJG-UHFFFAOYSA-N 2-amino-5-(4-chlorophenyl)-6-ethyl-2,3-dihydro-1H-pyrimidin-4-one Chemical compound NC1NC(=C(C(=N1)O)C1=CC=C(C=C1)Cl)CC TUBVXYXSEWNSJG-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- -1 2-acetyl-amino - 4 - chloro - 5 -p - chlorophenyl-6-ethylpyrimidine Chemical compound 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- VCPXZIUQCXEVCU-UHFFFAOYSA-N 4-ethylpyrimidine Chemical compound CCC1=CC=NC=N1 VCPXZIUQCXEVCU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
<B>Procédé de</B> préparation <B>d'un</B> dérivé <B>de la</B> pyrimidine La présente invention se rapporte à un pro cédé de préparation d'un dérivé de la pyrimi dine.
On connaît l'activité thérapeutique du com posé 2,4-diamino-5-p-chlorophényl-6-éthyl- pyrimidine contre le parasite paludéen, ce composé étant utilisé en clinique contre les in fections de malaria chez l'homme.
Il a été synthétisé par condensation d'un fl-éthyl-i3- alcoxyl-a-p-chlorophényl-acrylonitrile avec la guanidine. Il peut être synthétisé aussi par condensation dans l'oléum de l'éthyl-2-(p- chlorophényl)-3-pentanone-oate avec la gua- nidine, pour donner la 2-amino-4-hydroxy-5-p- chlorophényl-6-éthylpyrimidine, ce dernier composé, ou son dérivé 2-acétylamino,
étant chloré pour donner la 2-amino- ou la 2-acétyl- amino - 4 - chloro - 5 -p - chlorophényl-6-éthylpy- rimidine. Ce dernier corps, par chauffage avec de l'ammoniaque, est transformé en le com posé 2,4-diamino correspondant.
La présente invention concerne un autre procédé pour fabriquer le composé 2-amino-4- hydroxy - 5 -p-chlorophényl- 6 - éthylpyrimidine, qui peut être utilisé pour la préparation de la 2,4-diamino-5-p-chlorophényl-6-éthylpyrimi- dine.
On a trouvé qu'une 2-amino-4-hydroxy-5- p-chlorophényl-6-éthyldihydropyrimidine peut être déshydrogénée au moyen du soufre en la 2 - amino - 4 - hydroxy-5-p-chlorophényl-6-éthyl- pyrimidine. Ce composé peut être facilement converti en le composé 2,4-diamino par des méthodes connues.
La dihydropyrimidine peut être obtenue par condensation de la guanidine avec l'a-p- chlorophényl-,B-éthylacrylonitrile, pour donner une dihydropyrimidine qui peut avoir la struc ture représentée par les formules I, II ou III.
EMI0001.0052
La présente invention a pour objet un pro cédé de préparation de la 2-amino-4-hydroxy- 5-p-chlorophényl-6-éthylpyrimidine. Ce pro cédé est caractérisé en ce qu'on traite une 2-amino-4-hydroxy-5-p-chlorophényl-6-éthyl- dihydropyrimidine avec du soufre. . - <I>Exemple</I> On pulvérise 5,0 g de dihydropyrimidine et on la mélange intimement avec 12,0 g de soufre en poudre. On chauffe le mélange à 190-2100 C jusqu'à ce que la production d'hydrogène sul furé cesse (environ 3 heures).
L'excès de soufre est alors dissous dans du disulfure de carbone et le résidu insoluble est repris dans de l'hy droxyde de sodium. On précipite le produit avec de l'acide acétique. Le produit est purifié par dissolution dans l'hydroxyde de sodium dilué, traitement au carbone et cristallisation par addition de la solution alcaline à de l'acide acétique dilué bouillant.
Il se sépare sous forme d'aiguilles incolores (3,5 g) fondant à 2710 C, et il est, identique sous tous rapports à la 2-ami- no - 4 - hydroxy- 5 -p - chlorophényl -6-éthylpyri- midine préparée par d'autres méthodes.
Par acylation avec de l'anhydride acétique, on obtient un dérivé acétyle fondant à 2620 C, identique aux dérivés préparés à partir d'autres échantillons de l'amino-hydroxypyrimidine.
<B> Process for </B> preparation <B> of </B> derivative <B> of </B> pyrimidine The present invention relates to a process for preparing a derivative of pyrimidine .
The therapeutic activity of the compound 2,4-diamino-5-p-chlorophenyl-6-ethyl-pyrimidine against the malaria parasite is known, this compound being used clinically against malaria infections in humans.
It was synthesized by condensation of β-ethyl-13-alkoxyl-α-p-chlorophenyl-acrylonitrile with guanidine. It can also be synthesized by condensation in oleum of ethyl-2- (p-chlorophenyl) -3-pentanone-oate with guanidine, to give 2-amino-4-hydroxy-5-p- chlorophenyl-6-ethylpyrimidine, the latter compound, or its 2-acetylamino derivative,
being chlorinated to give 2-amino- or 2-acetyl-amino - 4 - chloro - 5 -p - chlorophenyl-6-ethylpyrimidine. The latter body, on heating with ammonia, is transformed into the corresponding 2,4-diamino compound.
The present invention relates to another process for making the compound 2-amino-4-hydroxy - 5 -p-chlorophenyl-6-ethylpyrimidine, which can be used for the preparation of 2,4-diamino-5-p-chlorophenyl-. 6-ethylpyrimidine.
It has been found that 2-amino-4-hydroxy-5-p-chlorophenyl-6-ethyldihydropyrimidine can be dehydrogenated by means of sulfur to 2-amino-4-hydroxy-5-p-chlorophenyl-6-ethyl- pyrimidine. This compound can be easily converted to the 2,4-diamino compound by known methods.
Dihydropyrimidine can be obtained by condensing guanidine with α-p-chlorophenyl-, B-ethylacrylonitrile, to give a dihydropyrimidine which may have the structure represented by formulas I, II or III.
EMI0001.0052
The present invention relates to a process for the preparation of 2-amino-4-hydroxy-5-p-chlorophenyl-6-ethylpyrimidine. This process is characterized in that a 2-amino-4-hydroxy-5-p-chlorophenyl-6-ethyl-dihydropyrimidine is treated with sulfur. . - <I> Example </I> 5.0 g of dihydropyrimidine is pulverized and it is thoroughly mixed with 12.0 g of powdered sulfur. The mixture is heated to 190-2100 ° C until the production of hydrogen sulphide ceases (about 3 hours).
The excess sulfur is then dissolved in carbon disulfide and the insoluble residue is taken up in sodium hydroxide. The product is precipitated with acetic acid. The product is purified by dissolving in dilute sodium hydroxide, treating with carbon and crystallizing by adding the alkaline solution to boiling dilute acetic acid.
It separates in the form of colorless needles (3.5 g) melting at 2710 C, and it is identical in all respects to 2-amino - 4 - hydroxy- 5 -p - chlorophenyl -6-ethylpyri- midine prepared by other methods.
By acylation with acetic anhydride, an acetyl derivative is obtained, melting at 2620 C, identical to the derivatives prepared from other samples of the amino-hydroxypyrimidine.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB314006X | 1952-04-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH314006A true CH314006A (en) | 1956-05-31 |
Family
ID=10322530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH314006D CH314006A (en) | 1952-04-01 | 1953-04-01 | Process for the preparation of a pyrimidine derivative |
Country Status (2)
| Country | Link |
|---|---|
| CH (1) | CH314006A (en) |
| DE (1) | DE934947C (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2579259A (en) * | 1951-12-18 | Iamino-s- | ||
| US2576939A (en) * | 1951-12-04 | -diamino-s-phenyl-e-alkyl- | ||
| US2602794A (en) * | 1952-07-08 | Process for preparation of x-amino-s |
-
1953
- 1953-03-31 DE DEW10923A patent/DE934947C/en not_active Expired
- 1953-04-01 CH CH314006D patent/CH314006A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE934947C (en) | 1955-11-10 |
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