CS218387B1 - 7-substitution derivatives of the 7h-benzo/c/fluorene - Google Patents
7-substitution derivatives of the 7h-benzo/c/fluorene Download PDFInfo
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- CS218387B1 CS218387B1 CS252781A CS252781A CS218387B1 CS 218387 B1 CS218387 B1 CS 218387B1 CS 252781 A CS252781 A CS 252781A CS 252781 A CS252781 A CS 252781A CS 218387 B1 CS218387 B1 CS 218387B1
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- Prior art keywords
- benzo
- fluorene
- hydroxy
- formula
- group
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- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 title 2
- 238000006467 substitution reaction Methods 0.000 title 1
- -1 3,9-Dimethyl-5- (2-diethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorene hydrochloride Chemical compound 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229910052801 chlorine Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- AMLZJBJUPQPFNG-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]-7h-benzo[c]fluoren-7-ol Chemical compound C12=CC=CC=C2C(OCCN(C)C)=CC2=C1C1=CC=CC=C1C2O AMLZJBJUPQPFNG-UHFFFAOYSA-N 0.000 claims description 3
- FRIJWEQBTIZQMD-UHFFFAOYSA-N Benzo[c]fluorene Chemical class C1=CC2=CC=CC=C2C2=C1CC1=CC=CC=C12 FRIJWEQBTIZQMD-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 241000193996 Streptococcus pyogenes Species 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 241000194032 Enterococcus faecalis Species 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
- WNLNIVVFWRVLTM-UHFFFAOYSA-N 5-[2-(diethylamino)ethoxy]-3,9-dimethylbenzo[c]fluoren-7-one Chemical compound C12=CC=C(C)C=C2C(OCCN(CC)CC)=CC2=C1C1=CC=C(C)C=C1C2=O WNLNIVVFWRVLTM-UHFFFAOYSA-N 0.000 description 1
- IALAUUKEGMAATC-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]benzo[c]fluoren-7-one Chemical compound C12=CC=CC=C2C(OCCN(C)C)=CC2=C1C1=CC=CC=C1C2=O IALAUUKEGMAATC-UHFFFAOYSA-N 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GOXIYIHTWMCOOR-UHFFFAOYSA-N Cl.C12=CC=CC=C2C(OCCN(C)C)=CC2=C1C1=CC=CC=C1C2O Chemical compound Cl.C12=CC=CC=C2C(OCCN(C)C)=CC2=C1C1=CC=CC=C1C2O GOXIYIHTWMCOOR-UHFFFAOYSA-N 0.000 description 1
- GJEPCLZVXSSTRW-UHFFFAOYSA-N F.F.F.Cl Chemical compound F.F.F.Cl GJEPCLZVXSSTRW-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001123227 Saccharomyces pastorianus Species 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Vynález se týká 7-substitučních derivátů 7H-benzo(c)fluorenu obecného vzorce IThe present invention relates to 7-substituted 7H-benzo (c) fluorene derivatives of formula (I)
ve kterémin which
R1 značí atom vodíku nebo methylskupinu,R 1 represents a hydrogen atom or a methyl group,
R2 seskupení obecného vzorce II —CIT2CH2N(R3)2 (II), kde R3 znáči methyl- nebo ethylskupinu nebo seskupení vzorce III —CH2—C(CH3)2—CH2N(CH3)2 (III), a X značí hydroxyskupinu nebo atom chloru, jakož i jejich adičních solí s farmaceuticky vhodnými kyselinami, zejména se silnými kyselinami organickými a anorganickými.R 2 groups of formula II -City 2 CH 2 N (R 3) 2 (II) wherein R 3 represents methyl or ethyl, or a group of the formula III, -CH 2 -C (CH 3) 2 -CH 2 N (CH 3 12 and X represents a hydroxy group or a chlorine atom, as well as their addition salts with pharmaceutically acceptable acids, in particular with strong organic and inorganic acids.
Vynález se rovněž týká adičních solí se silnými kyselinami organickými i anorganickými.The invention also relates to addition salts with strong organic and inorganic acids.
Látky obecného vzorce I, o výše uvedeném významu R1, R2, R3 a X jsou deriváty benzo(c)fluorenu, o nichž je známo, že v závislosti na druhu substituentu a jeho poloze na aromatickém skeletu, vykazují různé biologické účinnosti potenciálně použitelné v humánní i veterinární medicíně (viz např. čsl. autorská osvědčení č. 204 211, 202 213, 200 094). Autoři vynálezu nyní nalezli, že látky obecného vzorce I vykazují antibakteriální účinnost in vitro, která je charakterizována hodnotou minimální inhibiční koncentrace (MIC) vyjádřená v ^g/ /ml, testované na bakteriích (Streptococcus pyogenes Cl, Streptococcus faecalis, Staphylococcus pyogenes, Mycobacterium tuberculosis), dvou druzích kvasinek (Saccharomyces pastorianus, Trichophyton mentagrophytes) a dvou druzích plísní (Candida albicans, Aspergillus niger).The compounds of formula I, as defined above for R 1 , R 2 , R 3 and X, are benzo (c) fluorene derivatives which are known to exhibit different biological activities potentially depending on the type of substituent and its position on the aromatic skeleton. can be used in human and veterinary medicine (see eg Czech author's certificates No. 204 211, 202 213, 200 094). The present inventors have now found that the compounds of formula I exhibit in vitro antibacterial activity, characterized by a minimum inhibitory concentration (MIC) value expressed in µg / ml, tested on bacteria (Streptococcus pyogenes C1, Streptococcus faecalis, Staphylococcus pyogenes, Mycobacterium tuberculosis ), two yeast species (Saccharomyces pastorianus, Trichophyton mentagrophytes) and two mold species (Candida albicans, Aspergillus niger).
Testované látky vykázaly slabý účinek na kvasinky i plísně, s hodnotou MIC = 50 /ťg/ml. Výraznější aktivita byla zjištěna u bakterií. Tak např. 5-(2-dimethylaminoethoxy) -7-hydroxy-7H-benzo (c jf luorenhydr ochlorid vykazuje účinek proti Streptococcus pyogenes, Escherichia coli a Mycobacterium tuberculosis a hodnotu MIC = 6,25 ,ug/ml a proti Streptococcus faecalis a Streptococcus pyogenes hodnotu MIC = 50 ,ug/ml; 3,9-dimethyl-5- (2-diethylaminoethoxy) -7-hydroxy-7H-benzo(c)fluorenhydroehlorid vykazuje následující hodnoty MIC: (^g/mlj Streptococcus pyogenes Cl (6,25), Streptococcus faecalis (25,0), Streptococcus pyogenes (12,5). Escherichia coli (25,0) a Mycobacterium tuberculosis (12,5); 5-[2-(dimethylamino) ethoxy ] -7-chlor-7H-benzo (c) fluorenhydrochlorid vykazuje MIC = 6,25 ^g/ml u Streptococcus pyogenes, Escherichia coli a Mycobacterium tuberculosis a MIC = 12,5 ^ig/ml u Streptococcus faecalis, Staphylococcus pyogenes.The test substances showed a weak effect on both yeast and fungi, with a MIC value of 50 µg / ml. More significant activity was found in bacteria. Thus, for example, 5- (2-dimethylaminoethoxy) -7-hydroxy-7H-benzo (fluorofluoride chloride has an action against Streptococcus pyogenes, Escherichia coli and Mycobacterium tuberculosis and an MIC value of 6.25 µg / ml and against Streptococcus faecalis and Streptococcus pyogenes MIC value = 50 µg / ml; 3,9-dimethyl-5- (2-diethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorene hydrochloride shows the following MIC values: (µg / ml Streptococcus pyogenes Cl ( 6.25), Streptococcus faecalis (25.0), Streptococcus pyogenes (12.5), Escherichia coli (25.0) and Mycobacterium tuberculosis (12.5); 5- [2- (dimethylamino) ethoxy] -7- chloro-7H-benzo (c) fluorene hydrochloride shows MIC = 6.25 µg / ml in Streptococcus pyogenes, Escherichia coli and Mycobacterium tuberculosis and MIC = 12.5 µg / ml in Streptococcus faecalis, Staphylococcus pyogenes.
Ke stanovení aktivity byla použita diluční metoda, pro bakteriální kmeny v živném bujónu č. 2 (IMUNA), pro Mycobacterium tuberculosis půda podle Šuly (IMUNA) a pro kvasinky a plísně Sabouraudova tekutá půda.The dilution method was used to determine activity, for bacterial strains in Nutrient Broth # 2 (IMUNA), for Mycobacterium tuberculosis by Shula (IMUNA) soil, and for yeast and fungi Sabouraud's liquid soil.
Látky obecného vzorce I, ve kterém R1 a R2 mají výše uvedený význam a kde X značí hydroxyskupinu, se podle vynálezu připravují z látek obecného vzorce IVCompounds of formula I in which R 1 and R 2 are as defined above and where X represents OH, according to the invention are prepared from compounds of formula IV
ve kterém R1 má výše uvedený význam a R2 značí seskupení obecného vzorce II, nebo vzorce III, redukci 7-oxoskupiny působením natriumborohydridu, v množství 20 až 40 molekvivalentů, v prostředí nižšího alkoholu, výhodně v ethanolu, v rozmezí teplot od 20 °C do teploty varu reakční směsi.wherein R 1 is as defined above and R 2 represents a group of formula II or formula III, reduction of the 7-oxo group by treatment with sodium borohydride in an amount of 20 to 40 molar equivalents, in a lower alcohol, preferably ethanol, in the temperature range from 20 ° C to the boiling point of the reaction mixture.
Látka obecného vzorce I, ve kterém R1 značí atom vodíku, R2 značí seskupení vzorce II, ve kterém R3 značí methylskupinu, a X značí atom chloru, se podle vynálezu připravuje z látky obecného vzorce I, ve kterém R1 značí atom vodíku, R2 značí seskupení vzorce II, ve kterém R3 značí methylskupinu, a X značí hydroxyskupinu, reakcí s 5 až 10 molekvivalenty thionylchloridu v prostředí benzenu při teplotě varu reakční směsi.A compound of formula I wherein R 1 is hydrogen, R 2 is a group of formula II in which R 3 is methyl, and X is chlorine is prepared according to the invention from a compound of formula I in which R 1 is hydrogen R @ 2 denotes a group of formula II in which R @ 3 denotes methyl, and X denotes hydroxy by reaction with 5 to 10 mol equivalents of thionyl chloride in benzene at the boiling point of the reaction mixture.
Redukce 7-oxoskupiny na 7-hydroxyskupinu lze provést i za použití jiných postupů, i jiných činidel, např. komplexních hydridů, alkalických kovů nebo alkoholátů kovů ve vhodném prostředí, tlakových redukčních postupů a takových podmínek, které nepovedou k destrukci etherické vazby v poloze 5.Reduction of the 7-oxo group to the 7-hydroxy group can also be accomplished using other methods, including other reagents, such as complex hydrides, alkali metals or metal alcoholates in a suitable environment, pressure reduction procedures and conditions that will not destroy the ether bond at the 5-position. .
Použiti natriumborohydridu se jeví však jako nejjednodušší z hlediska přípravy a provedení reakce. Podobně i k výměně 7-hydroxyskupiny za atom chloru lze použít i jiných činidel; použití thionylchloridu se však jeví jako nejschůdnější a nejekonomičtější.However, the use of sodium borohydride appears to be the easiest to prepare and carry out the reaction. Similarly, other reagents may be used to exchange the 7-hydroxy group for a chlorine atom; however, the use of thionyl chloride appears to be the most feasible and economical.
Látky obecného vzorce I, nesoucí bazickou skupinu v etherické vázané části lze připravit jednak ve formě bází nebo ve formě adičních solí se silnými kyselinami, které lze považovat z farmaceutického hlediska za vyhovující. Zvláště vhodné se z hlediska rozpustnosti jeví použití adičních solí s kyselinou chlorovodíkovou.The compounds of formula (I) bearing a basic group in the ether bonded moiety can be prepared either in the form of bases or in the form of strong acid addition salts, which can be considered pharmaceutically acceptable. The use of hydrochloric acid addition salts appears to be particularly suitable from the standpoint of solubility.
Reakční směsi se po proběhnutí reakcí zpracovávají obvyklými postupy, např. se odpaří k suchu a surové produkty se po úpravě pH přečistí krystaíizací nebo sloupcovou chromatografií. Adiční soli se nejlépe přečistí krystaíizací. Látky obecného vzorce IV, používané jako výchozí suroviny, jsou látky známé a snadno získatelné. Podrobnější údaje o přípravě látek vyplynou z následujících příkladů provedení, které rozsah vynálezu neomezují.After the reactions have been completed, the reaction mixtures are worked up according to conventional methods, for example, evaporated to dryness and the crude products are purified by crystallization or by column chromatography after pH adjustment. The addition salts are best purified by crystallization. The compounds of formula (IV) used as starting materials are known and readily obtainable. The following non-limiting examples illustrate the preparation of the compounds.
PřikladlHe did
3,9-dimethyl-5- (2-diethylamirioethoxy) -7-hydroxy-7H-benzO'(c)fluorenhydrochlorid3,9-Dimethyl-5- (2-diethylamirioethoxy) -7-hydroxy-7H-benzo (c) fluorene hydrochloride
K suspenzi 500 mg (1,2 mmol) 3,9-dimethyl-5-( 2-diethylaminoethoxy )-7-oxo-7H-benzo(c)fluorenu ve 20 ml ethanolu se po částech přidá 1,5 g (40 mmol) natriumborohydridu a reakční směs se míchá při teplotě místnosti 6 hodin a pak se odpaří k suchu. Surový produkt se rozmíchá s vodou, okyselí kyselinou chlorovodíkovou a vyjme do chloroformu. Chloroformový extrakt se zalkalizuje vytřepáním nasyceným roztokem uhličitanu sodného, po vysušení odpaří a přečistí chromatografií na sloupci silikagelu za použití chloroformu jako elučního činidla. Spojené jednotné frakce se rozpustí v ethanolu a okyselí se ethanolickým roztokem chlorovodíku a zahuštěním se získá látka o teplotě tání 180 až 182 °C. Analogickým postupem byly připraveny:To a suspension of 500 mg (1.2 mmol) of 3,9-dimethyl-5- (2-diethylaminoethoxy) -7-oxo-7H-benzo (c) fluorene in 20 mL of ethanol was added portionwise 1.5 g (40 mmol) of The reaction mixture was stirred at room temperature for 6 hours and then evaporated to dryness. The crude product is stirred with water, acidified with hydrochloric acid and taken up in chloroform. The chloroform extract was basified by shaking with saturated sodium carbonate solution, evaporated after drying and purified by silica gel column chromatography using chloroform as eluent. The combined unitary fractions were dissolved in ethanol and acidified with ethanolic HCl solution and concentrated to give a melting point of 180-182 ° C. The following were prepared in an analogous way:
5- (2-diethylaminoethoxy) -7-hydroxy-7H-benzo(c)fluorenhydrochlorid o t. t. 122 až 124 °C (EtOH),5- (2-diethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorene hydrochloride, m.p. 122-124 ° C (EtOH),
GG
5-[ (3-dimethylamino) -2,2-dimethylpropoxy ]-7-hydroxy-7H-benzo (c jfluorenhydrochlorid o t. t. 241 až 244 °C (ethanol) a5 - [(3-dimethylamino) -2,2-dimethylpropoxy] -7-hydroxy-7H-benzo (trifluoride hydrochloride, m.p. 241 DEG-244 DEG C. (ethanol); and
5- (2-dimethylaminoethoxy) -7-hydroxy-7H-benzo(c)fluorenhydrochlorid o t. t. 224 až 230 °C (ethanol).5- (2-dimethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorene hydrochloride, m.p. 224-230 ° C (ethanol).
Příklad 2Example 2
5- (2-dimethylaminoethoxy) -7-hydroxy-7H-benzo(c)fluoren5- (2-dimethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorene
K suspenzi 500 mg (1,6 mmol) 5-(2-dimethylaminoethoxy ) -7-oxo-7H-benzo (c) fluorenu, ve 20 ml ethanolu se po částech přidá 1,5 g (40 mmol) natriumborohydridu a reakční směs se míchá při teplotě místnosti 6 hodin a odpaří se k suchu.To a suspension of 500 mg (1.6 mmol) of 5- (2-dimethylaminoethoxy) -7-oxo-7H-benzo (c) fluorene, in 20 ml of ethanol was added portionwise 1.5 g (40 mmol) of sodium borohydride and the reaction mixture. The mixture was stirred at room temperature for 6 hours and evaporated to dryness.
Surový produkt se rozmíchá s vodou, okyselí kyselinou chlorovodíkovou a vyjme do chloroformu. Chloroformový extrakt se zalkalizuje vytřepáním nasyceným roztokem uhličitanu sodného, po vysušení odpaří a přečistí chromatografií na sloupci silikagelu za použití chloroformu jako elučního' činidla. Spojením jednotných frakci a krystalizací v ethanolu se získá látka o t. t. 152 až 155 °C.The crude product is stirred with water, acidified with hydrochloric acid and taken up in chloroform. The chloroform extract was basified by shaking with saturated sodium carbonate solution, evaporated after drying and purified by silica gel column chromatography using chloroform as eluent. Combined fractions and crystallization in ethanol gave a melting point of 152-155 ° C.
Příklad 3Example 3
5- (2-dimethylaminoethoxy) -7-chlor-benzo(c) f luorenhydrochlorid5- (2-dimethylaminoethoxy) -7-chloro-benzo (c) fluorene hydrochloride
Suspenze 500 mg (1,6 mmol) 5-(2-dimethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorenu v 5 ml benzenu a 1 ml (1,77 g) (15 mmol) thionylchloridu se refluxuje 6 hodin. Vyloučený surový produkt se po ochlazení odsaje a přečistí krystaíizací ze směsi chloroform — hexan. Získá se látka o teplotě tání 198 až 200 °C.A suspension of 500 mg (1.6 mmol) of 5- (2-dimethylaminoethoxy) -7-hydroxy-7H-benzo (c) fluorene in 5 ml of benzene and 1 ml (1.77 g) (15 mmol) of thionyl chloride is refluxed for 6 hours . The precipitated crude product is suctioned off after cooling and purified by crystallization from chloroform-hexane. M.p. 198-200 ° C.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS252781A CS218387B1 (en) | 1981-04-03 | 1981-04-03 | 7-substitution derivatives of the 7h-benzo/c/fluorene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS252781A CS218387B1 (en) | 1981-04-03 | 1981-04-03 | 7-substitution derivatives of the 7h-benzo/c/fluorene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS218387B1 true CS218387B1 (en) | 1983-02-25 |
Family
ID=5362661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS252781A CS218387B1 (en) | 1981-04-03 | 1981-04-03 | 7-substitution derivatives of the 7h-benzo/c/fluorene |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS218387B1 (en) |
-
1981
- 1981-04-03 CS CS252781A patent/CS218387B1/en unknown
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