CH259701A - Process for the preparation of a biguanide derivative. - Google Patents
Process for the preparation of a biguanide derivative.Info
- Publication number
- CH259701A CH259701A CH259701DA CH259701A CH 259701 A CH259701 A CH 259701A CH 259701D A CH259701D A CH 259701DA CH 259701 A CH259701 A CH 259701A
- Authority
- CH
- Switzerland
- Prior art keywords
- chloro
- preparation
- methyl
- biguanide derivative
- bromophenyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 4
- 150000004283 biguanides Chemical class 0.000 title description 2
- QLYHPNUFNZJXOQ-UHFFFAOYSA-N 4-bromo-3-chloroaniline Chemical compound NC1=CC=C(Br)C(Cl)=C1 QLYHPNUFNZJXOQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 230000000078 anti-malarial effect Effects 0.000 claims 1
- 150000003839 salts Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- SWHSXWLSBBYLGM-UHFFFAOYSA-N 2-[(2-carboxyphenoxy)methoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCOC1=CC=CC=C1C(O)=O SWHSXWLSBBYLGM-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
- C07C279/26—X and Y being nitrogen atoms, i.e. biguanides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung eines Biguanidderivates. Die vorliegende Erfindung betrifft ein Verfahren zur Heisstellung von N'-3-Chlor-4- bromphen3#1- N' - methy 1-N'-isopropy lbiguanid, welches ein wertvolles chemotherapeutisches Mittel ist oder als Zwischenprodukt für die Herstellung von chemotherapeutischen Mitteln verwendet. werden kann. Es ist insbesondere ein wertvolles Antimalariamittel.
Erfindungsgemäss wird die besagte neue Verbindung, nämlich N'-3-Chlor-4-brom- phenyl-NS-inethyl-N5-isopropylbiguanid, da durch erhalten, dass man N3-Methyl-N'-iso- propyldicyandiamid mit 3-Chlor-4-bromanilin umsetzt.
Die Umsetzung erfolgt zweckmässig durch Erhitzen eines Salzes des Amins mit dem sub stituierten Dicyandiainid in Gegenwart eines Lösungsmittels, wie z. B. Wasser oder Äthoxyäthanol.
Das NI -3-Chlor-4-brotnphenyl-N5-methyl- N'-isopropylbiguanid stellt eine starke Base dar, welche mit organischen und anorgani- sehen Säuren beständige Salze ergibt, die in n.anelien Fällen in Wasser leielit löslieh sind.
Die Salze lassen sieh dadurch herstellen, da.ss die Base in wässrigen Lösungen der Säure gelöst und hierauf das Wasser verdampft wird, doch können sie in trockener Form be quemer durch Vermischen der Komponenten in einem organischen Lösungsmittel, wie z. B. Aceton, oder in einem Alkohol, in welchem die Salze spärlich löslich sind, hergestellt erden. Auf diese Weise kann man beispiels weise die Salze mit Essigsäure, Milchsäure, Methansulfonsäure, Methylendisalicylsäure, lIethylen-bis-ss-oxynaphthoesäure und Salz säure bequem herstellen.
Das folgende Beispiel diene zur Erläute rung der Erfindung. <I>Beispiel:</I> Ein Gemisch von 13,0 Teilen N--Methyl- N3-isopropyldicyandiamid und 24,3 Teilen 3 Chlor-4-broma.nilin-chlorhy drat in 80 Teilen f,-Äthoxyäthanol wird während 3 Stunden. unter R.ückfluss zum Sieden erhitzt. Hierauf lässt man das Gemisch abkühlen, worauf ab filtriert wird. Der feste Rückstand wird mit kaltem Äthylacetat gewaschen und aus Was ser umkristallisiert.
Auf diese Weise erhält man -NI - 3 - Chlor-4-bromphenyl-N' 1-nieth3#1-N- isopropylbiguanid in Form seines illonohydro- chlorids, welches bei 244 C schmilzt.
Process for the preparation of a biguanide derivative. The present invention relates to a process for the preparation of N'-3-chloro-4-bromophen3 # 1-N '-methy 1-N'-isopropylbiguanide, which is a valuable chemotherapeutic agent or used as an intermediate for the preparation of chemotherapeutic agents . can be. It is a particularly valuable antimalarial drug.
According to the invention, said new compound, namely N'-3-chloro-4-bromophenyl-NS-ynethyl-N5-isopropylbiguanide, is obtained because N3-methyl-N'-isopropyldicyandiamide is obtained with 3-chloro- 4-bromaniline converts.
The reaction is conveniently carried out by heating a salt of the amine with the sub-substituted dicyandiainide in the presence of a solvent, such as. B. water or ethoxyethanol.
The NI -3-chloro-4-brotnphenyl-N5-methyl-N'-isopropylbiguanide is a strong base which, with organic and inorganic acids, results in stable salts which, in normal cases, are easily soluble in water.
The salts can be prepared by dissolving the base in aqueous solutions of the acid and then evaporating the water, but they can be added in dry form by mixing the components in an organic solvent, e.g. B. acetone, or in an alcohol in which the salts are sparingly soluble, ground. In this way, for example, the salts with acetic acid, lactic acid, methanesulphonic acid, methylenedisalicylic acid, ethylene-bis-β-oxynaphthoic acid and hydrochloric acid can be conveniently prepared.
The following example serves to explain the invention. <I> Example: </I> A mixture of 13.0 parts of N-methyl-N3-isopropyldicyandiamide and 24.3 parts of 3-chloro-4-broma.nilin-chlorohydrate in 80 parts of f, -ethoxyethanol is used during 3 Hours. heated to boiling under R. reflux. The mixture is then allowed to cool, whereupon it is filtered off. The solid residue is washed with cold ethyl acetate and recrystallized from What water.
In this way, -NI - 3 - chloro-4-bromophenyl-N '1-nieth3 # 1-N-isopropyl biguanide is obtained in the form of its illonohydrochloride, which melts at 244.degree.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB259701X | 1945-10-08 | ||
| GB170946X | 1946-09-17 | ||
| CH254800T | 1946-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH259701A true CH259701A (en) | 1949-01-31 |
Family
ID=27178057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH259701D CH259701A (en) | 1945-10-08 | 1946-10-08 | Process for the preparation of a biguanide derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH259701A (en) |
-
1946
- 1946-10-08 CH CH259701D patent/CH259701A/en unknown
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