CS235174B1 - Method of 2-chlor-8-fluoro-6,11-dihydrodibenzo-(b,e)-thiepin derivatives preparation - Google Patents
Method of 2-chlor-8-fluoro-6,11-dihydrodibenzo-(b,e)-thiepin derivatives preparation Download PDFInfo
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- CS235174B1 CS235174B1 CS781583A CS781583A CS235174B1 CS 235174 B1 CS235174 B1 CS 235174B1 CS 781583 A CS781583 A CS 781583A CS 781583 A CS781583 A CS 781583A CS 235174 B1 CS235174 B1 CS 235174B1
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- dihydrodibenzo
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- 238000002360 preparation method Methods 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 5
- GBQFYIYBAUYADB-UHFFFAOYSA-N 2-chloro-8-fluoro-6,11-dihydrobenzo[c][1]benzothiepine Chemical class ClC1=CC2=C(SCC3=C(C2)C=CC(=C3)F)C=C1 GBQFYIYBAUYADB-UHFFFAOYSA-N 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- -1 1-methyl-4-piperidylidene Chemical group 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- 238000006297 dehydration reaction Methods 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 238000006386 neutralization reaction Methods 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims 2
- 238000010992 reflux Methods 0.000 claims 1
- 150000003509 tertiary alcohols Chemical class 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 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 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 1
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 1
- KKDJJBAMSYLYQS-UHFFFAOYSA-N 5-fluoro-3h-2-benzofuran-1-one Chemical compound FC1=CC=C2C(=O)OCC2=C1 KKDJJBAMSYLYQS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000021962 pH elevation Effects 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- BISQTCXKVNCDDA-UHFFFAOYSA-N thiepine Chemical compound S1C=CC=CC=C1 BISQTCXKVNCDDA-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Vynález se týká způsobu přípravy derivátu 2-chlior-8-fluor-6,ll-dihydrodibenzo(b,e)thiepinu vzorce I,The invention relates to a process for the preparation of a 2-chloro-8-fluoro-6,11-dihydrodibenzo (b, e) thiepine derivative of the formula I,
tj. 2-chlor-8-fluor-ll- (l-methyl-4-piperidylidenj-6,ll-dihydrodibenzo(b,e jthiepinu, jakož i jeho solí s anorganickými nebo organickými kyselinami.i.e. 2-chloro-8-fluoro-11- (1-methyl-4-piperidylidene) -6,11-dihydrodibenzo (b, e-thiepine), as well as its salts with inorganic or organic acids.
Látka vzorce I je meziproduktem přípravy farmaikodynamicky účinných látek a sama o sobě vykazuje rovněž určité účinky. Byla testována ve formě hydrogenmaleinátu. Při orálním podání vyvolává u myší ataxii (diskoordinační účinek) v testu rotující tyčky; EDso = 15,9 mg/Rg (účinek doznívá do 24 hodin po- podání). V koncentraci 25 (Ug/ml působí inhibičně vůči růstu těchto mikroorganismů: Streptococcus ,3-haemolycus, Streptococcus faecalis, Staphylococcus pyogenes aureus a Escherichia coll. Způsob přípravy látky vzorce I podle tohoto vynálezu spočívá v kysele kátalyzované dehydrataci terciárního' alkoholu vzorce IIThe compound of formula (I) is an intermediate in the preparation of pharmacodynamically active substances and, in itself, also has certain effects. It was tested in the form of hydrogen maleate. When administered orally, it induces ataxia (discoordinating effect) in mice in a rotating rod test; ED 50 = 15.9 mg / Rg (effect resolved within 24 hours of dosing). At a concentration of 25 (Ug / ml), it inhibits the growth of the following microorganisms: Streptococcus, 3-haemolycus, Streptococcus faecalis, Staphylococcus pyogenes aureus and Escherichia coll.
která se s výhodou provede varem ze směsí kyseliny octové a acetylchloridu. Látka vzorce II je látka nová a její příprava je popsána v příkladu. Látka vzorce I rezultuje jako olejovitá báze, která se neutralizací převede na: krystalický maleinát a v této formě se vyčistí krystalizaeí. Rozkladem této čisté soli alkalízací lze získat homogenní olejovitou bázi I. Identita konečného produktu vzorce I i všech nových meziproduktů byla zajišitěna analýzami a pomocí spekter. Po235174 drobnosti provedení přípravy látky vzorce I podle tohoto vynálezu jsou uvedeny v příkladu, jehož účelem je ilustrovat možnosti vynálezu, ale ne všechny tyto možnosti vyčerpávajícím způsobem popisovat.which is preferably carried out by boiling from a mixture of acetic acid and acetyl chloride. The compound of formula II is novel and its preparation is described in the example. The compound of formula I results in an oily base which is converted to crystalline maleate by neutralization and purified in this form by crystallization. Decomposition of this pure salt by alkalinization yields a homogeneous oily base I. The identity of the end product of formula I as well as of all novel intermediates was assured by analyzes and spectra. The details of the preparation of the compound of formula (I) according to the invention are given in an example which is intended to illustrate the possibilities of the invention, but not all of these possibilities are exhaustively described.
Směs 8,5 g surové báze 2-chlor-8-fluor-ll-(l-methyl-4-piperidyl)-6,ll-dihydrodibenzo(b,e)ithiepin-ll-olu, 85 ml kyseliny octové a 25 ml acetylchloridu se míchá a zahřívá 3 hodiny pod zpětným chladičem na 100 °C. Po stání přes noc se zředí vodou, zalkalizuje se vodným amoniakem a extrahuje dichlormethanem. Extrakt se vysuší uhličitanem draselným a odpaří. Tmavý zbytek se rozpustí v benzenu a chromatografuje se na sloupci 250 g neutrálního oxidu hlinitého (aktivita IIj. Benzenem se eluuje 3,4 gramu (42 °/o) homogenní olejovité báze 2-chlor-8-f luor-11- (l-methyl-4-piperidyliden]-6,ll-dihydrodibenzo(b,e) thiepinu vzorce I, která se neutralizuje pomocí 1,2 g kyseliny maleinové v ethanolu. Krystalizaci se získá 4,0 hydrogenmaleinátu tajícího při 172 až 175 °C (ethanol-ether). Rozkladem maleinátu mírným přebytkem vodného amoniaku a extrakcí etherem se získá homogenní olejovitá báze vzorce I, která je vhodná pro další zpracování a pro měření spektra. . Výchozí 2-chlor-8-f luor-11- (l-methyl-4-piperidyl) -6,11-dihydrodibenzo (b,e) thiepin-ll-ol je látkou novou, která se získá ze známých výchozích látek například tímto způsobem:A mixture of 8.5 g of crude 2-chloro-8-fluoro-11- (1-methyl-4-piperidyl) -6,11-dihydrodibenzo (b, e) ithiepine-11-ol base, 85 ml of acetic acid and 25 ml of acetyl chloride was stirred and refluxed at 100 ° C for 3 hours. After standing overnight, dilute with water, basify with aqueous ammonia and extract with dichloromethane. The extract was dried over potassium carbonate and evaporated. The dark residue is dissolved in benzene and chromatographed on a 250 g neutral alumina column (activity IIj. 3.4 g (42%) of a homogeneous oily base of 2-chloro-8-fluoro-11- (1- methyl 4-piperidylidene] -6,11-dihydrodibenzo (b, e) thiepine of formula I which is neutralized with 1.2 g of maleic acid in ethanol to give 4.0 hydrogen maleate melting at 172-175 ° C (ethanol) By decomposing the maleate with a slight excess of aqueous ammonia and extracting with ether, a homogeneous oily base of formula I is obtained, which is suitable for further processing and for the measurement of the spectrum. 4-piperidyl) -6,11-dihydrodibenzo (b, e) thiepine-11-ol is a novel substance which is obtained from known starting materials, for example, as follows:
Ve 150 mil l-butanolu se rozpustí 7,5 g kovového sodíku, k roztoku butoxidu se přidá 47 g 4-chlorthiofenolu a směs se míchá 10 minut. Potom se přidá 50 g 5-fluorftalidu (M. Rajšer a M. Protiva, Collect. Czech, Chem;. Commun. 32, 2021, 1967) a směs se míchá a vaří 4 hodiny pod zpětným chladičem,. Rozpouštědlo se odpaří za sníženého tlaku, zbytek se rozpustí ve vodě, roztok se zfiltruje s karborafinem a filtrát se okyselí kyselinou chlorovodíkovou. Po stání přes noc se vyloučená kyselina 2-(4-chlorfeny*lthiomethylj-4-fluorbenzoová odsaje, promyje se vodou a vysuší ve vakuu. Získá se ve výtěžku 83 g (96 %.) a po krystalizaci z cyklohexanu taje při 144 až 146 °C.7.5 g of sodium metal are dissolved in 150 ml of 1-butanol, 47 g of 4-chlorothiophenol are added to the butoxide solution and the mixture is stirred for 10 minutes. 50 g of 5-fluorophthalide (M. Rajser and M. Protiva, Collect. Czech, Chem .; Commun. 32, 2021, 1967) are then added and the mixture is stirred and refluxed for 4 hours. The solvent was evaporated under reduced pressure, the residue was dissolved in water, the solution was filtered with carboraffin and the filtrate acidified with hydrochloric acid. After standing overnight, the precipitated 2- (4-chlorophenylthiomethyl) -4-fluorobenzoic acid was filtered off with suction, washed with water and dried in vacuo to give a yield of 83 g (96%) and melted at 144-146 after crystallization from cyclohexane. Deň: 32 ° C.
Směs 21,9 g předešlé kyseliny a 250 g kyseliny polyfosforečné se míchá 8 hodin a zahřívá na 150 až 155 °C. Po ochlazení se rozloží vodou a ledem a produkt se extrahuje benzenem. Extrakt se promyje 5% roztokem hydroxidu sodného a vodou, vysuší se síranem 'hořečnatým1 a odpaří. Zbytek se krystalizuje z ethanolu. Ve výtěžku 14,5 g (71 procent) se získá 2-chlor-8-flu*ordibenzo(b,e)thiepin-ll(6H)-on tající v čistém stavu při 172 až 174°C (aceton).A mixture of 21.9 g of the previous acid and 250 g of polyphosphoric acid was stirred for 8 hours and heated to 150-155 ° C. After cooling, it is quenched with water and ice and the product is extracted with benzene. The extract was washed with 5% sodium hydroxide solution and water, dried over magnesium sulfate 1 and evaporated. The residue was crystallized from ethanol. Yield: 14.5 g (71%). 2-Chloro-8-fluoro-ordibenzo (b, e) thiepin-11 (6H) -one, m.p. 172 DEG-174 DEG C. (acetone).
Známým způsobem (E. Adlerová a spol., Česfc. Farm. 12, 122, 1963) se připraví Grignardovo činidlo z 5,0 g 4-chlor-l-methylpiperidinu a 0,9 g hořčíku ve 20 ml tetrahydrofuranu (iniciace zrnkem jodu a několika kapkami 1,2-dibromethanu) a za míchání při teplotě místnosti se přidá roztok 7,0 g předešlého ketonu v 50 ml benzenu (po; kapkách). Směs se vaří 2,5 hodiny pod zpětným chladičem a ponechá se při teplotě místnosti přes -noc v klidu. Potom se odpaří za sníženého tlaku, zbytek se rozloží roztokem chloridu amonného a extrahuje se benzenem, Extrakt se promyje vodou, vysuší se uhličitanem draselným a zfiltruje přes 3 cm vrstvu oxidu hlinitého. Odpařením filtrátu za sníženého* tlaku se získá 8,5 g (90 %) téměř homogenního' olejovitého 2-chlor-8-f luor-11- (l-methyl-4-piperidyl)-6,11dihydrodibenzo (b,e)thiepin-ll-olu (II), kterého se v tomto stavu použije k závěrečné dehydratační reakci. K vyčištění vzorku lze použít chromatografie na sloupci neutrálního* oxidu hlinitého (aktivita II). Benzenový eluát krystaluje jako modifikace A ze směsi benzenu a petroletheru a taje při 199 až 200° Celsia, Odpařením matečného louhu a krystalizací zbytku ze směsi benzenu a petroletheru se získá modifikace B tající při 176 až 178 °C. Obě modifikace poskytují analytická data v souhlase se sumárním složením C20H21CIFNOS, jejich 1H NMR spektra v* deuteriochloroformu jsou totožná, avšak jejich infračervená spektra v Nujolu vykazují zřetelné rozdíly.By the known method (E. Adler et al., Cesfc. Farm. 12, 122, 1963), a Grignard reagent was prepared from 5.0 g of 4-chloro-1-methylpiperidine and 0.9 g of magnesium in 20 ml of tetrahydrofuran (initiation by iodine grain) and a few drops of 1,2-dibromoethane) and with stirring at room temperature, a solution of 7.0 g of the previous ketone in 50 ml of benzene (dropwise) is added. The mixture was refluxed for 2.5 hours and allowed to stand at room temperature overnight. It is then evaporated under reduced pressure, the residue is quenched with ammonium chloride solution and extracted with benzene. The extract is washed with water, dried over potassium carbonate and filtered through a 3 cm layer of alumina. Evaporation of the filtrate under reduced pressure gave 8.5 g (90%) of an almost homogeneous oily 2-chloro-8-fluoro-11- (1-methyl-4-piperidyl) -6,11-dihydrodibenzo (b, e) thiepine -II-ol (II), which in this state is used for the final dehydration reaction. Neutral alumina column chromatography (activity II) can be used to purify the sample. The benzene eluate crystallizes as modification A from the benzene / petroleum ether mixture and melts at 199-200 ° C. Evaporation of the mother liquor and crystallization of the residue from the benzene / petroleum ether mixture yields modification B melting at 176-178 ° C. Both modifications provide analytical data in accordance with the overall composition of C20H21CIFNOS, their 1 H NMR spectra in deuteriochloroform being identical, but their infrared spectra in Nujol show marked differences.
Claims (2)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS781583A CS235174B1 (en) | 1983-10-24 | 1983-10-24 | Method of 2-chlor-8-fluoro-6,11-dihydrodibenzo-(b,e)-thiepin derivatives preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS781583A CS235174B1 (en) | 1983-10-24 | 1983-10-24 | Method of 2-chlor-8-fluoro-6,11-dihydrodibenzo-(b,e)-thiepin derivatives preparation |
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| Publication Number | Publication Date |
|---|---|
| CS235174B1 true CS235174B1 (en) | 1985-05-15 |
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|---|---|---|---|
| CS781583A CS235174B1 (en) | 1983-10-24 | 1983-10-24 | Method of 2-chlor-8-fluoro-6,11-dihydrodibenzo-(b,e)-thiepin derivatives preparation |
Country Status (1)
| Country | Link |
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| CS (1) | CS235174B1 (en) |
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1983
- 1983-10-24 CS CS781583A patent/CS235174B1/en unknown
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