CS268486B1 - Method of 2-(phenylthio) benzylamines and their hydrogen maleates preparation - Google Patents
Method of 2-(phenylthio) benzylamines and their hydrogen maleates preparation Download PDFInfo
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- CS268486B1 CS268486B1 CS887631A CS763188A CS268486B1 CS 268486 B1 CS268486 B1 CS 268486B1 CS 887631 A CS887631 A CS 887631A CS 763188 A CS763188 A CS 763188A CS 268486 B1 CS268486 B1 CS 268486B1
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- phenylthio
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- benzylamines
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- chloroform
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- 238000000034 method Methods 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- DJLYZQORDBVJFE-UHFFFAOYSA-N (2-phenylsulfanylphenyl)methanamine Chemical class NCC1=CC=CC=C1SC1=CC=CC=C1 DJLYZQORDBVJFE-UHFFFAOYSA-N 0.000 title claims abstract 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 title claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 20
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 8
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 2
- 239000001257 hydrogen Substances 0.000 claims abstract 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- COLPCCMCYYQDPN-UHFFFAOYSA-N 1-(chloromethyl)-2-phenylsulfanylbenzene Chemical compound ClCC1=CC=CC=C1SC1=CC=CC=C1 COLPCCMCYYQDPN-UHFFFAOYSA-N 0.000 claims description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 6
- 238000006386 neutralization reaction Methods 0.000 claims description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 11
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 abstract description 10
- 238000006243 chemical reaction Methods 0.000 abstract description 6
- 239000000935 antidepressant agent Substances 0.000 abstract description 2
- 229940005513 antidepressants Drugs 0.000 abstract description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 abstract description 2
- 229940073608 benzyl chloride Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 2
- 229960004801 imipramine Drugs 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- GIIKOPZJCKETRH-UHFFFAOYSA-N 1-[(2-phenylsulfanylphenyl)methyl]piperidine Chemical compound C=1C=CC=C(SC=2C=CC=CC=2)C=1CN1CCCCC1 GIIKOPZJCKETRH-UHFFFAOYSA-N 0.000 description 1
- YPHHLMXERAEIAI-UHFFFAOYSA-N 1-[(2-phenylsulfanylphenyl)methyl]pyrrolidine Chemical compound C=1C=CC=C(SC=2C=CC=CC=2)C=1CN1CCCC1 YPHHLMXERAEIAI-UHFFFAOYSA-N 0.000 description 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- -1 N- [2- (Phenylthio) benzyl] morpholine Chemical compound 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000000891 anti-reserpine Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- FUIKDYGWMKMQNR-UHFFFAOYSA-N n,n-dimethyl-1-(2-phenylsulfanylphenyl)methanamine Chemical compound CN(C)CC1=CC=CC=C1SC1=CC=CC=C1 FUIKDYGWMKMQNR-UHFFFAOYSA-N 0.000 description 1
- OMVKUCDWZIOJEC-UHFFFAOYSA-N n-methyl-1-(2-phenylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC=C1 OMVKUCDWZIOJEC-UHFFFAOYSA-N 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Řešeni spadá do oboru synthesy léčiv. Týká se způsobu přípravy 2-/fenylth1o/benzylamlnů I a jejich krystalických hydrogenmalelnátů. Base jsou meziprodukty přípravy dalších farmakodynamleky účinných látek zatím co hydrogenmaleináty Jsou účinné antlreserplnově, jsou potenciálními antidepreslvy. Způsob přípravy látek spočívá v reakcích 2-/fenylthio/ benzylchlorldu s d1methylam1nem, dlethylamlnem, pyrrolIdlnem, piperidlnem a morfoUnem použitými ve 100 až 120 X přebytku v chloroformu při teplotách 60 až 80 °C. Neutral1sac1 vzniklých olejovítých basi kyselinou malelnovou se získají krystalické hydrogenmaleináty.The solution falls within the field of drug synthesis. It relates to a process for the preparation of 2- (phenylthio) benzylamines I and their crystalline hydrogen maltates. Base are intermediates preparing other pharmacodynamics effective substances while hydrogen maleate They are effective antlreserpline, potential antidepressants. Method of preparation substances consists in the reactions of 2- / phenylthio / benzylchloride with methylamine, diethylamine, pyrrolide, piperidine and morpholine used in 100-120 X excess in chloroform at 60 to 80 ° C ° C. Neutral1sac1 formed oily with malelic acid are obtained crystalline hydrogen maleate.
Description
Tento vynález se týká způsobu přípravy 2-/fenylthío/benzylaminů obecného vzorce I, sc6H5 ch2r /1/, ve kterém R je zbytek dímethylamínu, diethylaaínu, pyrrolídinu, píperidinu a morfolinu, a jejich hydrogenmaleinátů.This invention relates to the preparation of 2- / phenylthio / benzylamines of the formula I, SC 6 H 5 CH 2 R / 1 / wherein R is the residue of dimethylamine, diethylamine, pyrrolidine, piperidine and morpholine, and hydrogen maleate.
Látky podle vynálezu vzorce I jsou meziprodukty přípravy dalších farmakodynamícky účinných sloučenin. Ve formě svých hydrogenmaleinátů orojevuji však samy o sobě použitelné farmakodynamícké efekty, v prvé řadě takové, které z nich činí potenciální antidepresiva.The compounds of the formula I according to the invention are intermediates for the preparation of further pharmacodynamically active compounds. However, in the form of their hydrogen maleates, I reveal the pharmacodynamic effects which can be used on their own, primarily those which make them potential antidepressants.
Typickou látkou podle vynálezu je N, N-dímethyl-2-/fenyI th io/benzy lamin /1, R = N/CHj/j/, jehož hydrogenmaleinát byl testován při orálním podání /kromě testů in vitro/. Jeho akutní toxicita u myši LD^g je 211 mg/kg. V testu reserpí nových vředů u krys má látka signifikantní inhibični účinek v dávce 50 mg/kg. Rovněž v testu reserpinové ptosy u myší vykazuje látka výrazný antireserpinový účinek; účinek je signifikantní v dávce 12,5 mg/kg a prahová účinná dávka je 3 mg/kg, což je obdobné jako u imipraminu. Látka výrazně inhibuje vazbu 4 nM /^H/imipraminu v hypothalamu krysího mozku; IC-- 3 i uA typical substance according to the invention is N, N-dimethyl-2- (phenylthio) benzylamine (1, R = N (CH 2) 3), whose hydrogen maleate has been tested for oral administration (except for in vitro tests). Its acute toxicity in LD50 mice is 211 mg / kg. In a test for new ulcers in rats, the substance has a significant inhibitory effect at a dose of 50 mg / kg. Also in the mouse reserpine ptosis test, the substance shows a significant antireserpine effect; the effect is significant at 12.5 mg / kg and the threshold effective dose is 3 mg / kg, which is similar to imipramine. The substance significantly inhibits the binding of 4 nM (1H) imipramine in the rat brain hypothalamus; IC-- 3 and u
13,54 nN. Podobně Inhibuje též vazbu 4 nM / H/desi pra mi nu v hypothalamu krysího mozku; ICSO = 16,6 n«. '13.54 nN. Similarly, it also inhibits 4 nM / H / desi pramin binding in the rat brain hypothalamus; IC SO = 16.6 n «. '
Látek podobných látkám podle vynálezu se týká US patent č. 4 018 830. Tento patent však konkrétně popisuje jedinou látku, tj. N-methy1-2-/Íenylthío/benzylamin /a jeho hydrogenma1einát/. K její přípravě používá zásadně jinou metodu, než jaká je předmětem vynálezu. Kromě toho látky, které jsou nekonkrétně v citovaném spisu uváděny /včetně jediné jmenované konkrétní l.átky jsou označovány jako ant i arytmíka, z čehož plyne, že způsob jejích použití je zcela jiný než způsob využiti láiek podle tohoto vynálezu vyrobených. Látky podle předloženého vynálezu jsou z hlediska vědeckého pojetí nové, tj. nebyly nikdy předtím v literatuře popsány a charakterizovány. Jejich identita byta zajištěna obvyklými analytickými a spektrálními metodami.Substances similar to the compounds of the invention are disclosed in U.S. Patent No. 4,018,830. However, this patent specifically discloses a single substance, i.e., N-methyl-2- (phenylthio) benzylamine (and its hydrogen maleate). It uses a fundamentally different method for its preparation than that which is the subject of the invention. In addition, substances which are specifically mentioned in the cited document / including the only named specific substance are referred to as anti-arrhythmics, which implies that the method of their use is completely different from the method of using the medicaments according to the invention. The substances according to the present invention are new from a scientific point of view, i.e. they have never been described and characterized in the literature before. Their identity is ensured by the usual analytical and spectral methods.
Látky vzorce I podle vynálezu se připraví substituční reakcí známého 2-/fenyI th i o/ benzylchloridu /Jílek J. 0. et al., Monatsh. Chem. 96, 182 /1965/; Jílek J. 0. et al., Collect. Czech. Chem. Commun. 32, 3186 /1967// se sekundárními aminy obecného vzorce H-R, ve kterém R značí totéž jako ve vzorci I. Reakce lze provést za různých podmínek, s výhodou v chloroformu při teplotách 60 až 80 °C. Nejvýhodnějši variantou je vaření směsi jmenovaného chloridu se 100 až 120 % přebytkem aminu H-R v chloroformu pod zpětným chladičem. Pokud toto nedovolí těkavost použitého aminu, provede se reakce v autoklavu. získané base se převedou neutralizaci kyselinou maleinovou na příslušné soli, tj. hydrogenmalefnáty. Další podrobnosti provedeni způsobu přípravy látek vzorce I podle vynálezu vyplývají z příkladů, které samozřejmě nepopisují všechny možností vynálezu.The compounds of formula I according to the invention are prepared by a substitution reaction of the known 2- (phenylthio) benzyl chloride [Jílek J. 0. et al., Monatsh. Chem. 96, 182 (1965); Jílek J. 0. et al., Collect. Czech. Chem. Commun. 32, 3186 (1967) with secondary amines of the general formula H-R, in which R is the same as in the formula I. The reaction can be carried out under various conditions, preferably in chloroform at temperatures of 60 to 80 ° C. The most preferred variant is the refluxing of a mixture of said chloride with a 100 to 120% excess of amine H-R in chloroform. If this does not allow the volatility of the amine used, the reaction is carried out in an autoclave. the bases obtained are converted by neutralization with maleic acid into the corresponding salts, i.e. hydrogen malonates. Further details of the process for the preparation of the compounds of the formula I according to the invention follow from the examples, which, of course, do not describe all the possibilities of the invention.
Přiklad 1Example 1
N,N-D1methyl-2-/fenylth1o/benzylaminN, N-D-methyl-2- (phenylthio) benzylamine
Roztok 11,7 g 2-/fenylthio/benzylchlorídu v 50 ml chloroformu se nasytí 9,0 g dímethylamínu a směs se zahřívá 12.h v autoklavu na 75 °C. Po ochladnutí se chloroform, odpaří a zbytek se rozdělí mezi 150 ml benzenu a 150 ml vody za přídavku 10 ml 10 roztoku hydroxidu sodného. Benzenová vrstva se promyje vodou a báze se z ní extrahuje do 15C ml 1,5N HCl. Vodný roztok spolu s vyloučeným olejovitým hydrochloridem se zalkalízuje vod2 . CS268486 B1 ným amoniakem a báze se extrahuje benzenem. Zpracování extraktu se získá 12,0 g surové báze, která se předestíluje ve vakuu; 10,6 g /87 X/, t. v. 128 až 129 °C/50 °a. Neutralizaci kyselinou maleinovou v acetonu poskytuje krystalický hydrogenmaleinát, který z acetonu krystalizuje a v čistém stavu taje při 144 °c.A solution of 11.7 g of 2- (phenylthio) benzyl chloride in 50 ml of chloroform was saturated with 9.0 g of dimethylamine and the mixture was heated in an autoclave at 75 ° C for 12 h. After cooling, chloroform was evaporated and the residue was partitioned between 150 ml of benzene and 150 ml of water with the addition of 10 ml of sodium hydroxide solution. The benzene layer was washed with water and the base was extracted into 15 ml of 1.5 N HCl. The aqueous solution together with the precipitated oily hydrochloride is basified with water2. CS268486 B1 ammonia and the base is extracted with benzene. Work-up of the extract gave 12.0 g of crude base, which was distilled in vacuo; 10.6 g (87%), m.p. 128-129 ° C (50 ° C). Neutralization with maleic acid in acetone gives crystalline hydrogen maleate, which crystallizes from acetone and melts in pure form at 144 ° C.
Příklad 2 ·Example 2 ·
N,N-Blethy1-2-/fenyIthío/benzylaminN, N-Blethyl-2- (phenylthio) benzylamine
Smis 11,7 g 2-/fenylthio/benzylchlorídu, 50 ml chloroformu a 14,6 g díethylaminu se vaří 8 h pod zpitným chladičem a zpracuje se podobni jako v předešlém příkladu. Získá se 10,8 g /80 %/ olejovítého produktu vroucího pří 133 až 135 °C/50 Pa. Poskytuje krystalický hydrogenmaleínát tající při 68 až 69 °C /acetcn-ether/. 'A mixture of 11.7 g of 2- (phenylthio) benzyl chloride, 50 ml of chloroform and 14.6 g of diethylamine was refluxed for 8 hours and worked up as in the previous example. 10.8 g (80%) of an oily product boiling at 133 DEG-135 DEG C./50 Pa are obtained. It gives a crystalline hydrogen maleate melting at 68-69 ° C (acetyl ether). '
Přiklad 3Example 3
N-/2-/FenyIthio/benzyl/pyrrolidínN- [2- (Phenylthio) benzyl] pyrrolidine
Podobná reakce 11,7 g 2-fenylthío/benzylchloridu a 14,2 g pyrrolidinu v 50 ml vroucího chloroformu poskytne 10,2 g /76 %/ olejovlté báze, b. v. 143 až 145 °c/50 Pa. Poskytuje krystalický hydrogenmaleínát tající pří 93 až 94 °C /aceton-ether/.A similar reaction of 11.7 g of 2-phenylthio / benzyl chloride and 14.2 g of pyrrolidine in 50 ml of boiling chloroform gives 10.2 g (76%) of an oily yellow base, m.p. 143-145 ° C / 50 Pa. It gives a crystalline hydrogen maleate melting at 93-94 ° C (acetone ether).
Příklad 4Example 4
N-/2-/Fenylthío/benzyl/piperidinN- [2- (Phenylthio) benzyl] piperidine
Podobná reakce 11,7 g 2-/fenylthío/benzylchloridu a 17,0 g piperidinu v 50 ml vroucího chloroformu poskytuje 10,7 g /76 %/ olejovlté báze vroucí při 146 až 150 °C/60 Pa. Báze poskytuje krystalický hydrogenmaleínát, t. t. 102 až 103 °C /aceton-ether/.A similar reaction of 11.7 g of 2- (phenylthio) benzyl chloride and 17.0 g of piperidine in 50 ml of boiling chloroform gives 10.7 g (76%) of an oily yellow base boiling at 146-150 ° C / 60 Pa. The base gives crystalline hydrogen maleate, m.p. 102-103 ° C (acetone ether).
Příklad 5Example 5
N-/2-/Fenylthío/benzyl/morfolínN- [2- (Phenylthio) benzyl] morpholine
Podobná reakce 11,7 g 2-/fenylthio/benzylchloridu a 17,4 g morfolinu v 50 ml vroucího chloroformu dává 11,9 g /84 Z/ olejovíti báze vroucí při 159 až 161-?C. Neutralizací kyselinou malelnovou poskytuje krystalický hydrogenmaleínát, t. t. 118 až 119 °C /aceton-ether/.A similar reaction of 11.7 g of 2- (phenylthio) benzyl chloride and 17.4 g of morpholine in 50 ml of boiling chloroform gives 11.9 g (84%) of an oily base boiling at 159-161 ° C. Neutralization with malic acid gives crystalline hydrogen maleate, mp 118-119 ° C (acetone-ether).
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CS887631A CS268486B1 (en) | 1988-11-21 | 1988-11-21 | Method of 2-(phenylthio) benzylamines and their hydrogen maleates preparation |
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---|---|---|---|
CS887631A CS268486B1 (en) | 1988-11-21 | 1988-11-21 | Method of 2-(phenylthio) benzylamines and their hydrogen maleates preparation |
Publications (2)
Publication Number | Publication Date |
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CS763188A1 CS763188A1 (en) | 1989-08-14 |
CS268486B1 true CS268486B1 (en) | 1990-03-14 |
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CS887631A CS268486B1 (en) | 1988-11-21 | 1988-11-21 | Method of 2-(phenylthio) benzylamines and their hydrogen maleates preparation |
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CS (1) | CS268486B1 (en) |
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1988
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CS763188A1 (en) | 1989-08-14 |
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