CH299941A - Process for the preparation of a pyrimidine derivative. - Google Patents
Process for the preparation of a pyrimidine derivative.Info
- Publication number
- CH299941A CH299941A CH299941DA CH299941A CH 299941 A CH299941 A CH 299941A CH 299941D A CH299941D A CH 299941DA CH 299941 A CH299941 A CH 299941A
- Authority
- CH
- Switzerland
- Prior art keywords
- sep
- preparation
- pyrimidine derivative
- methyl
- ethanol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000003230 pyrimidines Chemical class 0.000 title description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 5
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 238000012512 characterization method Methods 0.000 claims 1
- 229960004198 guanidine Drugs 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- JDRJWFLOZMCQMW-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-3-oxobutanenitrile Chemical compound CC(=O)C(C#N)C1=CC=C(Cl)C(Cl)=C1 JDRJWFLOZMCQMW-UHFFFAOYSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Procédé de préparation d'un dérivé de la pyrimidine. La présente invention a pour objet un pro <B>cédé</B> de fabrication dun nouveau composé, la 2,4-diamino-5-(3',4#-dichloro,phényl)-6-méthyl- pyrimidine.
Il a été trouvé que<B>ce</B> composé a des pro- Priétés précieuses par le traitement de la ma laria humaine. On le prépare, selon la pré sente invention, en f aisant réagir un P-alcoy'- oxy- <B>fi</B> -méthy <B>1-</B> a<B>-</B> (3,4<B>-</B> diehlorophényl) <B>-</B> acrylo- nitrile avec de la guanidine. Ce composé cristallise<B>à</B> partir d'éthanol et a un point de fusion de 274-275" <B>C.</B>
L'aerylonitrile susmentionné peut être préparé en partant d'a-acétyl-a-(3,4-dichloro- phényl) -acétonitrile, en faisant réagir ce der nier avec un agent d'alcoylation, par exemple le diazométhane. Comme le groupe alcoyle (R) contenu dans le groupe alcoyloxy n'entre pas dans le produit final, tout groupe alcoyle convenable peut être employé. Ces réactions s'effectuent comme indiqué ci-après:
EMI0001.0025
<I>Exemple:</I> Le produit de départ a été préparé comme suit.
On a chauffé de l'a-acétyl-a-(3,4-dichloro- phényl)-acétonitrile, ayant un point de fu sion de<B>161-1630 C</B> (11,4<B>g),</B> avec de l'orthoaeétate de méthyle<B>(25</B> ml). Les pro duits<B>à</B> bas point d'ébullition ont été éliminés tant qu'ils ont continué<B>à</B> se former. L'ortho- ester a alors été enlevé par distillation dans le vide.
Le produit s'est solidifié et, par re- cristallisation <B>à</B> partir d'éthanol, il a formé des plaques<B>à</B> point de fusion de 71-74" <B>C</B> (C,,H±)ONC12: calculé<B>N 5,8;</B> trouvé<B>6,0).</B>
On a condensé cet a-(3,4-clichlorophényl)- méthoxy-fl-méthyl- acrylonitrile avec une solution de guanidine dans de l'éthanol <B>(50</B> ml) préparée avec 4,7<B>g</B> de son chlorhy- drate. La solution a été chauffée avec reflux pendant 2 heures, l'alcool a été éliminé et le
EMI0002.0001
résidu <SEP> a <SEP> été <SEP> traité <SEP> avec <SEP> de <SEP> la <SEP> soude <SEP> caust.iqLie
<tb> <B>5 <SEP> N.</B> <SEP> La <SEP> substance <SEP> insoluble <SEP> a <SEP> été <SEP> alors <SEP> filtrée.
<tb> Après <SEP> purification <SEP> par <SEP> précipitation,
<SEP> avec <SEP> de
<tb> la <SEP> soude <SEP> caustique, <SEP> d'une <SEP> solution <SEP> dans <SEP> -de
<tb> l'acide <SEP> acétique <SEP> dilué <SEP> et <SEP> recristallisation <SEP> dans
<tb> de <SEP> Èéthanol, <SEP> le <SEP> produit <SEP> avait <SEP> -un <SEP> point <SEP> de <SEP> fu sion <SEP> de <SEP> <B>274-2750 <SEP> C.</B>
<tb>
Calculé <SEP> pour <SEP> C,,I-I,()N4CI2 <SEP> <B>- <SEP> N <SEP> 20,9.</B>
<tb> Trouvé <SEP> <B>N</B> <SEP> 21,2.
Process for the preparation of a pyrimidine derivative. The present invention relates to a <B> assigned </B> process for the manufacture of a new compound, 2,4-diamino-5- (3 ', 4 # -dichloro, phenyl) -6-methyl-pyrimidine.
<B> this </B> compound has been found to have valuable properties in the treatment of human ma laria. It is prepared, according to the present invention, by reacting a P-alkyl-oxy- <B> fi </B> -méthy <B> 1- </B> a <B> - </B> (3,4 <B> - </B> diehlorophenyl) <B> - </B> acrylonitrile with guanidine. This compound crystallizes <B> from </B> from ethanol and has a melting point of 274-275 "<B> C. </B>
The above-mentioned aerylonitrile can be prepared starting from α-acetyl-α- (3,4-dichlorophenyl) -acetonitrile, by reacting the latter with an alkylating agent, for example diazomethane. Since the alkyl group (R) contained in the alkyloxy group does not enter into the final product, any suitable alkyl group can be employed. These reactions are carried out as indicated below:
EMI0001.0025
<I> Example: </I> The starting material was prepared as follows.
Α-Acetyl-α- (3,4-dichlorophenyl) -acetonitrile, having a melting point of <B> 161-1630 C </B> (11.4 <B> g ), </B> with methyl orthoaeetate <B> (25 </B> ml). The low boiling <B> </B> products have been eliminated as long as they continue to <B> to </B> form. The orthoester was then removed by vacuum distillation.
The product solidified and on recrystallization <B> from </B> from ethanol, it formed plaques <B> with </B> melting point of 71-74 "<B> C </B> (C ,, H ±) ONC12: calculated <B> N 5.8; </B> found <B> 6.0). </B>
This a- (3,4-clichlorophenyl) - methoxy-fl-methyl-acrylonitrile was condensed with a solution of guanidine in ethanol <B> (50 </B> ml) prepared with 4.7 <B> g </B> of its hydrochloride. The solution was heated with reflux for 2 hours, the alcohol was removed and the
EMI0002.0001
residue <SEP> has <SEP> been <SEP> treated <SEP> with <SEP> of <SEP> the <SEP> soda <SEP> caust.iqLie
<tb> <B> 5 <SEP> N. </B> <SEP> The <SEP> substance <SEP> insoluble <SEP> has <SEP> been <SEP> then <SEP> filtered.
<tb> After <SEP> purification <SEP> by <SEP> precipitation,
<SEP> with <SEP> from
<tb> the <SEP> caustic <SEP> soda, <SEP> of a <SEP> solution <SEP> in <SEP> -de
<tb> <SEP> acetic acid <SEP> diluted <SEP> and <SEP> recrystallization <SEP> in
<tb> of <SEP> ethanol, <SEP> the <SEP> product <SEP> had <SEP> -a <SEP> point <SEP> of <SEP> fusion <SEP> of <SEP> <B> 274 -2750 <SEP> C. </B>
<tb>
Calculated <SEP> for <SEP> C ,, I-I, () N4CI2 <SEP> <B> - <SEP> N <SEP> 20.9. </B>
<tb> Found <SEP> <B> N </B> <SEP> 21.2.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US299941XA | 1950-12-30 | 1950-12-30 | |
| CH297992T | 1951-06-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH299941A true CH299941A (en) | 1954-06-30 |
Family
ID=25733914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH299941D CH299941A (en) | 1950-12-30 | 1951-06-13 | Process for the preparation of a pyrimidine derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH299941A (en) |
-
1951
- 1951-06-13 CH CH299941D patent/CH299941A/en unknown
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