CH506474A - 2-aminochlorobenzylamines antipyretics secretolytics - Google Patents
2-aminochlorobenzylamines antipyretics secretolyticsInfo
- Publication number
- CH506474A CH506474A CH1643866A CH1643866A CH506474A CH 506474 A CH506474 A CH 506474A CH 1643866 A CH1643866 A CH 1643866A CH 1643866 A CH1643866 A CH 1643866A CH 506474 A CH506474 A CH 506474A
- Authority
- CH
- Switzerland
- Prior art keywords
- sep
- inorganic
- radicals
- formula
- amines
- Prior art date
Links
- TUCGRWZMAZDCRT-UHFFFAOYSA-N NC1=C(CNCl)C=CC=C1 Chemical class NC1=C(CNCl)C=CC=C1 TUCGRWZMAZDCRT-UHFFFAOYSA-N 0.000 title claims description 4
- 230000001754 anti-pyretic effect Effects 0.000 title abstract description 3
- 239000002221 antipyretic Substances 0.000 title abstract description 3
- 229940125716 antipyretic agent Drugs 0.000 title abstract 2
- 239000002253 acid Substances 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- -1 secretolytics Substances 0.000 claims abstract description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000012433 hydrogen halide Substances 0.000 claims description 5
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 235000005985 organic acids Nutrition 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 150000007530 organic bases Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 230000000954 anitussive effect Effects 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 239000003434 antitussive agent Substances 0.000 abstract 1
- 229940124584 antitussives Drugs 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QPKNLTFEHMEHJU-UHFFFAOYSA-N CC(=O)N(C(C)=O)C1=C(CBr)C(Cl)=CC=C1 Chemical compound CC(=O)N(C(C)=O)C1=C(CBr)C(Cl)=CC=C1 QPKNLTFEHMEHJU-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000020176 deacylation Effects 0.000 description 1
- 238000005947 deacylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- KIJXMUOJNZXYHU-UHFFFAOYSA-N n-propan-2-ylpropan-2-amine;hydrobromide Chemical compound [Br-].CC(C)[NH2+]C(C)C KIJXMUOJNZXYHU-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
(a) Cmpds. of general formula (I) R' and R2 = opt. unsat. lower alkyl, hydroxyalkyl, cycloalkyl, opt. subst. aryl or opt. subst. aralkyl. or - = a 5-7 membered heterocyclic ring opt. contng. a second N atom. X = 3- or 6- Cl. (b) Acid addn. salts of I. Antipyretics, secretolytics, and antitussives.
Description
Verfahren zur Herstellung von neuen 2-Amino-chlor-benzyl-aminen
Die Erfindung betrifft die Herstellung von neuen 2-Amino-chlor-benzyl-aminen der Formel I
EMI1.1
in der das Chloratom in 3- oder 6-Stellung und R1 und R2, die gleich oder verschieden sind und geradkettige oder verzweigte, gesättigte oder ungesättigte niedere aliphatische Kohlenwasserstoffreste, Hydroxyalkyl-, Cycloalkyl-, Aryl-, substituierte Aryl-, Aralkyl- oder substituierte Aralkylreste bedeuten, oder R1 und Re zusammen mit dem benachbaren Stickstoffatom einen gegebenenfalls durch niedre Alkylreste substituierten fünfbis siebengliedrigen gesättigten heterocyclischen Ring bedeuten, der durch ein weiteres Stickstoffatom unterbrochen sein kann.
Die Erfindung betrifft ferner die Herstellung der physiologisch verträglichen Säureadditionssalze mit anorganischen oder organischen Säuren.
Erfindungsgemäss erfolgt die Herstellung der neuen Verbindungen durch Umsetzung von Mono- oder Di acylamido-chlor-benzyl-halogeniden der Formel II
EMI1.2
in der Hal Brom oder Chlor, R3 Wasserstoff oder einen Acylrest und Rd einen Acylrest bedeuten, mit Aminen der Formel III
EMI1.3
in Gegenwart halogenwasserstoffbindender Mittel und anschliessende Abspaltung der Acylreste.
Als halogenwasserstoffbindendes Mittel kann eine anorganische oder tertiäre organische Base oder auch ein Überschuss des eingesetzten Amins der Formel III dienen, wobei pro Mol der Reaktionskomponenten ein Überschuss von mindestens einem Mol eingesetzt wird.
Die Umsetzung erfolgt zweckmässig in Gegenwart eines inerten organischen Lösungsmittels, beispielsweise Tetrachlorkohlenstoff, Äthanol, Aceton, Benzol, Toluol und bei erhöhten Temperaturen, vorzugsweise bei dem Siedepunkt des verwendeten Lösungsmittels. Falls ein Überschuss des Amins der Formel III oder eine tertiäre organische Base als halogenwasserstoffbindendes Mittel verwendet wird, können diese gleichzeitig auch als Lösungsmittel dienen.
Die Entacylierung kann in üblicher Weise erfolgen, vorzugsweise durch Erhitzen mit verdünnten Mineralsäuren oder verdünnten anorganischen Basen.
Die als Ausgangsstoffe verwendeten Verbindungen der Formel II sind aus der Literatur bekannt oder können nach literaturbekannten Verfahren hergestellt werden. So können beispielsweise die 2-Diacylamino-chlorbenzylhalogenide der Formel II aus den entsprechenden 2-Diacylamino-chlor-toluolen durch Umsetzung mit N Bromsuccinimid bzw. mit Chlor oder Brom unter UV Bestrahlung hergestellt werden.
Die erhaltenen Verbindungen können mit anorganischen oder organischen Säuren in üblicher Weise in ihre physiologisch verträglichen Säureadditionssalze überführt werden. Als Säuren haben sich beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Milchsäure, Zitronensäure, Weinsäure und Maleinsäure als geeignet erwiesen. Die Säureadditionssalze sind wasserlöslich, praktische Verwendung finden vor allem Salze mit 1, 2 und 3 Äquivalenten der betreffenden Säure, je nach der Anzahl der basischen Gruppen.
Die erfindungesgemäss hergestellten Verbindungen weisen wertvolle pharmakologische Eigenschaften auf, sie zeigen insbesondere neben antipyretischer und sekretolytischer Aktivität eine sehr gute hustenstillende Wirkung bei geringer Toxizität.
Beispiel I N,N-Diisopropyl-(2-amino-6-cS110r-benzyl)-amin
Zu einer Lösung von 56,3 g 6-Chlor-2-diacetylamino-benzyl-bromid in 0,9 1 Tetrachlorkohlenstoff werden 39,4 g Diisopropylamin gegeben. Das Reaktionsgemisch wird 1 Stunde am Rückfluss gekocht, anschliessend abgekühlt, das ausgefallene Diisopropylammonium-bromid abgesaugt und das Filtrat im Wasserstrahlvakuum eingeengt. Der verbliebene Rückstand wird in 520 cm3 Äthanol gelöst und nach Zusatz von 280 cm3 konzentrierter Salzsäure 20 Stunden am Rückfluss gekocht. Nach der Verseifung wird die Lösung eingeengt und der Rückstand in wenig absolutem Äthanol aufgenommen, wobei das N,N-Diisopropyl (2-amino-6-chlor-benzyl)-amin als Dihydrochlorid auskristallisiert.
Aus absolutem Äthanol umkristallisiert zeigt die Verbindung unter Zersetzung einen Schmelzpunkt von 198-2030 C.
In der folgenden Tabelle sind weitere Verbindungen angegeben, die erfindungsgemäss erhältlich sind.
EMI2.1
<tb>
Beispiel <SEP> Mal <SEP> R1 <SEP> R2 <SEP> F. <SEP> des <SEP> Dihydrochlorids, <SEP> 0
<tb> <SEP> 2 <SEP> 6-Cl <SEP> Methyl <SEP> Phenyl <SEP> 210-220 <SEP> (Zers.)
<tb> <SEP> 3 <SEP> 6-Ül <SEP> Butyl <SEP> Butyl <SEP> 174-178 <SEP> (Zers.)
<tb> <SEP> 4 <SEP> 6-C1 <SEP> Isobutyl <SEP> Isobutyl <SEP> 156-159 <SEP> (Zers.)
<tb> <SEP> 5 <SEP> 6-Cl <SEP> Amyl <SEP> Amyl <SEP> 152-158
<tb> <SEP> 6 <SEP> 6-C1 <SEP> Methyl <SEP> Cyclohexyl <SEP> 200-210 <SEP> (Zers.)
<tb> <SEP> 7 <SEP> 6-C1 <SEP> Äthyl <SEP> Cyclohexyl <SEP> 176-180 <SEP> (Zers.)
<tb> <SEP> R1 <SEP> ¯¯
<tb> <SEP> 8 <SEP> 6-C1 <SEP> N <SEP> = <SEP> NX <SEP> zu <SEP> 205-208 <SEP> (Zers.)
<tb> <SEP> Rs
<tb> <SEP> R1
<tb> <SEP> R1 <SEP> /CH2-CH2-CH2
<tb> <SEP> 9 <SEP> 6-Cl <SEP> -N <SEP> = <SEP> -N <SEP> | <SEP> 193-197 <SEP> (Zers.)
<tb> <SEP> \R2 <SEP> \CH2-CH=CH2
<tb> <SEP> 10 <SEP> 3-Cl <SEP> Propyl <SEP> Propyl
<SEP> 172-180
<tb> <SEP> 11 <SEP> 3-Cl <SEP> Isopropyl <SEP> Isopropyl <SEP> Hydrochlorid <SEP> 181-186 <SEP> (Zers.)
<tb> <SEP> 12 <SEP> 3-C1 <SEP> Butyl <SEP> Butyl <SEP> 158-167
<tb> <SEP> 13 <SEP> 3-C1 <SEP> Isobutyl <SEP> Isobutyl <SEP> 167-174
<tb> <SEP> 14 <SEP> 3-C1 <SEP> Amyl <SEP> Amyl <SEP> 144-150
<tb> <SEP> 15 <SEP> 3-Cl <SEP> Methyl <SEP> Cyclohexyl <SEP> 165-173
<tb> <SEP> 16 <SEP> 3-C1 <SEP> Äthyl <SEP> Cyclohexyl <SEP> Hydrochlorid <SEP> 177-179
<tb> <SEP> CH3
<tb> <SEP> 17 <SEP> 3-C1 <SEP> NÄRl <SEP> = <SEP> -N <SEP> zu <SEP> Hydrochlorid <SEP> 225-226 <SEP> (Zers.)
<tb> <SEP> Rs
<tb> <SEP> 18 <SEP> 3-C1 <SEP> Methyl <SEP> Benzyl <SEP> Hydrochlorid <SEP> 193-194
<tb>
Process for the preparation of new 2-amino-chloro-benzyl-amines
The invention relates to the preparation of new 2-amino-chloro-benzyl-amines of the formula I.
EMI1.1
in which the chlorine atom in the 3- or 6-position and R1 and R2, which are identical or different and are straight-chain or branched, saturated or unsaturated lower aliphatic hydrocarbon radicals, hydroxyalkyl, cycloalkyl, aryl, substituted aryl, aralkyl or substituted Aralkyl radicals, or R1 and Re together with the adjacent nitrogen atom represent a five to seven-membered saturated heterocyclic ring which is optionally substituted by lower alkyl radicals and which can be interrupted by a further nitrogen atom.
The invention also relates to the preparation of the physiologically acceptable acid addition salts with inorganic or organic acids.
According to the invention, the new compounds are prepared by reacting mono- or di-acylamido-chlorobenzyl halides of the formula II
EMI1.2
in which Hal is bromine or chlorine, R3 is hydrogen or an acyl radical and Rd is an acyl radical, with amines of the formula III
EMI1.3
in the presence of hydrogen halide binding agents and subsequent cleavage of the acyl radicals.
An inorganic or tertiary organic base or an excess of the amine of the formula III used can serve as the hydrogen halide-binding agent, an excess of at least one mole being used per mole of the reaction components.
The reaction is advantageously carried out in the presence of an inert organic solvent, for example carbon tetrachloride, ethanol, acetone, benzene, toluene and at elevated temperatures, preferably at the boiling point of the solvent used. If an excess of the amine of the formula III or a tertiary organic base is used as the hydrogen halide binding agent, these can also serve as a solvent at the same time.
The deacylation can be carried out in a customary manner, preferably by heating with dilute mineral acids or dilute inorganic bases.
The compounds of the formula II used as starting materials are known from the literature or can be prepared by processes known from the literature. For example, the 2-diacylamino-chlorobenzyl halides of the formula II can be prepared from the corresponding 2-diacylamino-chloro-toluenes by reaction with N bromosuccinimide or with chlorine or bromine under UV radiation.
The compounds obtained can be converted into their physiologically acceptable acid addition salts using inorganic or organic acids in the customary manner. As acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid and maleic acid have proven to be suitable. The acid addition salts are water-soluble; in practice, salts with 1, 2 and 3 equivalents of the acid in question are mainly used, depending on the number of basic groups.
The compounds prepared according to the invention have valuable pharmacological properties; in addition to antipyretic and secretolytic activity, they show, in particular, a very good antitussive effect with low toxicity.
Example I N, N-Diisopropyl- (2-amino-6-cS110r-benzyl) -amine
39.4 g of diisopropylamine are added to a solution of 56.3 g of 6-chloro-2-diacetylamino-benzyl bromide in 0.9 l of carbon tetrachloride. The reaction mixture is refluxed for 1 hour, then cooled, the diisopropylammonium bromide which has precipitated is filtered off with suction and the filtrate is concentrated in a water-jet vacuum. The remaining residue is dissolved in 520 cm3 of ethanol and, after addition of 280 cm3 of concentrated hydrochloric acid, refluxed for 20 hours. After the saponification, the solution is concentrated and the residue is taken up in a little absolute ethanol, the N, N-diisopropyl (2-amino-6-chlorobenzyl) amine crystallizing out as dihydrochloride.
Recrystallized from absolute ethanol, the compound exhibits a melting point of 198-2030 ° C. with decomposition.
The following table shows further compounds which can be obtained according to the invention.
EMI2.1
<tb>
Example <SEP> times <SEP> R1 <SEP> R2 <SEP> F. <SEP> of the <SEP> dihydrochloride, <SEP> 0
<tb> <SEP> 2 <SEP> 6-Cl <SEP> Methyl <SEP> Phenyl <SEP> 210-220 <SEP> (decomp.)
<tb> <SEP> 3 <SEP> 6-Ül <SEP> Butyl <SEP> Butyl <SEP> 174-178 <SEP> (decomp.)
<tb> <SEP> 4 <SEP> 6-C1 <SEP> isobutyl <SEP> isobutyl <SEP> 156-159 <SEP> (decomp.)
<tb> <SEP> 5 <SEP> 6-Cl <SEP> Amyl <SEP> Amyl <SEP> 152-158
<tb> <SEP> 6 <SEP> 6-C1 <SEP> methyl <SEP> cyclohexyl <SEP> 200-210 <SEP> (decomp.)
<tb> <SEP> 7 <SEP> 6-C1 <SEP> Ethyl <SEP> Cyclohexyl <SEP> 176-180 <SEP> (decomp.)
<tb> <SEP> R1 <SEP> ¯¯
<tb> <SEP> 8 <SEP> 6-C1 <SEP> N <SEP> = <SEP> NX <SEP> to <SEP> 205-208 <SEP> (dec.)
<tb> <SEP> Rs
<tb> <SEP> R1
<tb> <SEP> R1 <SEP> / CH2-CH2-CH2
<tb> <SEP> 9 <SEP> 6-Cl <SEP> -N <SEP> = <SEP> -N <SEP> | <SEP> 193-197 <SEP> (dec.)
<tb> <SEP> \ R2 <SEP> \ CH2-CH = CH2
<tb> <SEP> 10 <SEP> 3-Cl <SEP> Propyl <SEP> Propyl
<SEP> 172-180
<tb> <SEP> 11 <SEP> 3-Cl <SEP> isopropyl <SEP> isopropyl <SEP> hydrochloride <SEP> 181-186 <SEP> (decomp.)
<tb> <SEP> 12 <SEP> 3-C1 <SEP> Butyl <SEP> Butyl <SEP> 158-167
<tb> <SEP> 13 <SEP> 3-C1 <SEP> isobutyl <SEP> isobutyl <SEP> 167-174
<tb> <SEP> 14 <SEP> 3-C1 <SEP> Amyl <SEP> Amyl <SEP> 144-150
<tb> <SEP> 15 <SEP> 3-Cl <SEP> Methyl <SEP> Cyclohexyl <SEP> 165-173
<tb> <SEP> 16 <SEP> 3-C1 <SEP> ethyl <SEP> cyclohexyl <SEP> hydrochloride <SEP> 177-179
<tb> <SEP> CH3
<tb> <SEP> 17 <SEP> 3-C1 <SEP> NÄRl <SEP> = <SEP> -N <SEP> to <SEP> hydrochloride <SEP> 225-226 <SEP> (decomp.)
<tb> <SEP> Rs
<tb> <SEP> 18 <SEP> 3-C1 <SEP> methyl <SEP> benzyl <SEP> hydrochloride <SEP> 193-194
<tb>
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1643866A CH506474A (en) | 1963-10-14 | 1966-11-16 | 2-aminochlorobenzylamines antipyretics secretolytics |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DET24890A DE1226115B (en) | 1963-10-14 | 1963-10-14 | Process for the preparation of new amino-halogen-benzylamines |
| US40333964A | 1964-10-12 | 1964-10-12 | |
| DET0028358 | 1965-04-09 | ||
| CH1643866A CH506474A (en) | 1963-10-14 | 1966-11-16 | 2-aminochlorobenzylamines antipyretics secretolytics |
| GB54637/66A GB1154547A (en) | 1963-10-14 | 1966-12-06 | Substituted Benzylamines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH506474A true CH506474A (en) | 1971-04-30 |
Family
ID=27509533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1643866A CH506474A (en) | 1963-10-14 | 1966-11-16 | 2-aminochlorobenzylamines antipyretics secretolytics |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH506474A (en) |
-
1966
- 1966-11-16 CH CH1643866A patent/CH506474A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |