CS261332B1 - Esters of arylalkane acids with 1,2-diglycerides and method of their production - Google Patents
Esters of arylalkane acids with 1,2-diglycerides and method of their production Download PDFInfo
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- 239000002253 acid Substances 0.000 title claims abstract description 21
- 150000007513 acids Chemical class 0.000 title claims abstract description 12
- 150000002148 esters Chemical class 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 3
- -1 carbon chain saturated Chemical group 0.000 claims abstract description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims abstract description 4
- LHOIAFAJRRSRRQ-UHFFFAOYSA-N 1,1-dimethyl-2-pyridin-4-ylhydrazine Chemical compound CN(C)NC1=CC=NC=C1 LHOIAFAJRRSRRQ-UHFFFAOYSA-N 0.000 claims abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 230000003197 catalytic effect Effects 0.000 claims abstract description 3
- 150000004820 halides Chemical class 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 3
- VRWJOISQKOAUMR-UHFFFAOYSA-N n,n-dibutylpyridin-4-amine Chemical compound CCCCN(CCCC)C1=CC=NC=C1 VRWJOISQKOAUMR-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims abstract description 3
- 150000004670 unsaturated fatty acids Chemical group 0.000 claims abstract description 3
- 238000000605 extraction Methods 0.000 claims abstract 2
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract description 2
- 150000001412 amines Chemical class 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 238000004821 distillation Methods 0.000 abstract 1
- 235000003441 saturated fatty acids Nutrition 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 125000005633 phthalidyl group Chemical group 0.000 description 2
- QEGGEIPOBKSVQQ-UHFFFAOYSA-N 2-(N,2-dichloroanilino)-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)N(Cl)C1=CC=CC=C1Cl QEGGEIPOBKSVQQ-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Abstract
Estery arylalkanových kyselin s 1,2- -diglyceridy obecného vzorce I, kde R značí uhlíkatý řetězec nasycené nebo nenasycené mastné kyseliny obsahující 11 až 19 atomů uhlíku, R1 značí vodík nebo methyl, Ar značí 4-isobutylfenyl-, 6-methoxy-2-naftyl-, 2- -fluor-4-bifenyl- nebo /1-(4-chlorbenzoyl)- -5-methoxy-2-methylíndol-3-yl/-skupinu, patří do skupiny nesteroidních protizánětlivých léčiv. Způsob jejich výroby spočívá v tom, že se na substituované arylalkanové kyseliny obecného vzorce II, kde Ar a Rl mají shora uvedený význam, ve formě halogenidu působí 1,2-diglyceridem obecného vzorce III, kde R má shora uvedený význam, při teplotě 0 až 50 °C v prostředí terciárního aminu s výhodou pyridinu, triethylaminu, ethyldiisopropylaminu popřípadě za přítomnosti katalytického mnžoství 4-dimethylamino- nebo 4-dibutylaminopyridinu po dobu 1 až 12 hodin, načež se po zředění reakční směsi vodou, případně po předchozím oddestilováni rozpouštědla za sníženého tlaku, izoluje extrakcí organickým rozpouštědlem produkt obecného vzorce I.1,2-Esters of arylalkanoic acids -diglycerides of formula I wherein R is carbon chain saturated or unsaturated fatty acids containing 11 to 19 atoms carbon, R 1 is hydrogen or methyl, Ar is 4-isobutylphenyl-, 6-methoxy-2-naphthyl-, 2- -fluoro-4-biphenyl- or 1- (4-chlorobenzoyl) - -5-methoxy-2-methylindol-3-yl / group, belongs to the group of non-steroidal anti-inflammatory drugs drugs. The way they are made rests in that it is substituted arylalkanoic acids of formula II, wherein Ar and R1 are as defined above in the form of a halide treated with 1,2-diglyceride of formula III, wherein R is as defined above, at 0 to 50 ° C in a tertiary environment amine, preferably pyridine, triethylamine, ethyldiisopropylamine optionally in the presence of of catalytic quantities of 4-dimethylamino- or 4-dibutylaminopyridine for a period of time 1 to 12 hours, after which the reaction was diluted with water, or after distillation solvents under reduced pressure it is isolated by extraction with an organic solvent the product of formula (I).
Description
Vynález se týká esterů arylalkanových kyselin s 1,2-diglyceridy obecného vzorce I,The invention relates to arylalkanoic acid esters of the 1,2-diglycerides of the general formula I,
RCOOCHRCOOCH
I 2 I 2
RCOOCHRCOOCH
ArCHCOOCH, íl1 (I) kde R značí uhlíkatý řetězec nasycené nebo nenasycené mastné kyseliny obsahující 11 až 19 atomů uhlíku, r' značí vodík nebo methylArCHCOOCH, clay 1 (I) wherein R denotes a carbon chain of a saturated or unsaturated fatty acid containing from 11 to 19 carbon atoms, r 'denotes hydrogen or methyl
Ar značí 4-isobutylfenyl-, 6-methoxy-2-naftyl-, 2-fluor-4-bifenylyl- nebo /1-(4-chlorbenzoyl) -5-n\ethoxy-2-methylindol-3-yl) -skupinu.Ar is 4-isobutylphenyl-, 6-methoxy-2-naphthyl-, 2-fluoro-4-biphenylyl- or 1- (4-chlorobenzoyl) -5-methoxy-2-methylindol-3-yl) .
Uvedené estery obecného vzorce I patří do skupiny nesteroidních protizánětlivých léčiv (Čs. farmacie 29, 309 (1980); Chronicles of Drugs Discovery, J. Wiley, New York 1981; J. Pharm Sci, 73, 579 (1984)). V řadě případů bylo prokázáno, že estery 2-arylalkanových kyselin vykazují vyšSÍ analgetickou a protizánětlivou účinnost než volné kyseliny. NSR pat. spis Ger. Offen. 3 043 712 chrání ftalidylestery arylalkanových kyselin jako ftalidyl-3-(4-isobutylfenyl) propionát, ftalidyl-d-2-(6-methoxy-2-naftyl)propionát, ftalidyl-2-(3-benzoylfenyl)propionát a další. Tyto látky vykazují prokazatelně vyšší protizánětlivou a analgatickou účinnost než odpovídající matečné kyseliny, a to i v lékových formách. Ve švýcarských patentních spisech 579 051 a 594 625 jsou chráněny (2-pyridyl)methyl-, (3-pyridyl)methyl-, (4-pyridyl)methyl-, 3-(4-pyridyl)propylestery kyseliny o-(2,6-dichloranilino)fenyloctové a dalších příbuzných kyselin, které vedle protizánětlivých a analgetických účinků se osvědčily jako filtry proti nebezpečnému krátkovlnnému slunečnímu zářeni. Zvláště výrazná analgetická účinnost (Euro pat. spis 166 135) byla prokázána u /4-(2-hydroxy-2-propyl)-1-(cyklohexen-l-yl/methylesteru kyseliny 2-(6-methoxy-2-naftyl)propionové, který mimoto vykazuje 3krát vyšší toleranci na gastrointestinální trakt. V belg. pat. spise 887 460 jsou chráněny estery polyethylenglykolů s arylpropionovými kyselinami se srovnatelnou účinností matečných kyselin, ale s protrahovanými účinky. Do stejné skupiny přísluší i 2,3,4,6-tetraacetyl-l-/2-(4-isobutylfenyl)propionyl/-beta-D-glukopyranosa a 2,3,4,6-tetraacetyl-l-/2-(6-methoxy-2-naftyl)propionyl/-beta-D-glukopyranosa (Indián, J. Chem., Séct. Β 25B, 337 (1986)). Dalši terapeutické použiti (Euro pat. 70 717) nalezly také při léčení akutního respiračního syndromu.The esters of formula (I) belong to the group of non-steroidal anti-inflammatory drugs (Pharm. Pharm. 29, 309 (1980); Chronicles of Drugs Discovery, J. Wiley, New York 1981; J. Pharm. Sci, 73, 579 (1984)). In many cases, 2-arylalkanoic acid esters have been shown to have higher analgesic and anti-inflammatory activity than free acids. NSR pat. spis Ger. Offen. 3,043,712 protects phthalidyl esters of arylalkanoic acids such as phthalidyl-3- (4-isobutylphenyl) propionate, phthalidyl-2- (6-methoxy-2-naphthyl) propionate, phthalidyl 2- (3-benzoylphenyl) propionate and others. These substances have been shown to have greater anti-inflammatory and analgatic activity than the corresponding parent acids, even in dosage forms. Swiss Patent Nos. 579,051 and 594,625 disclose (2-pyridyl) methyl-, (3-pyridyl) methyl-, (4-pyridyl) methyl-, 3- (4-pyridyl) propyl esters of o- (2,6) (Dichloroanilino) phenylacetic acid and other related acids which, in addition to anti-inflammatory and analgesic effects, have proved to be filters against dangerous shortwave solar radiation. Particularly pronounced analgesic efficacy (Euro Pat. 166,135) has been demonstrated for 2- (6-methoxy-2-naphthyl) [4- (2-hydroxy-2-propyl) -1- (cyclohexen-1-yl) methyl ester. In addition, in patent specification 887 460, esters of polyethylene glycols with arylpropionic acids with comparable efficacy of the parent acids, but with protracted effects, are protected in the same group. -tetraacetyl-1- [2- (4-isobutylphenyl) propionyl] -beta-D-glucopyranose and 2,3,4,6-tetraacetyl-1- [2- (6-methoxy-2-naphthyl) propionyl] -beta -D-Glucopyranose (Indian, J. Chem., S ct 25B, 337 (1986)) Other therapeutic uses (Euro Pat. 70,717) have also been found in the treatment of acute respiratory syndrome.
V poslední době (Folia pharmacol. japon. 88, 33-40, 77-84 a 205-213 (1986)) byly do klinické praxe zavedeny nové estery 1-(4-chlorbenzoyl)-5-methoxy-3-methylindol-3-yloctové kyseliny s protizánětlivou účinností volné kyseliny (léčivo indomethacin), ale s podstatně nižším ulcerogenním účinkem (1/7 až 1/10 indomethacinu) vedle menšího inhibičního účinku na biosyntézu prostaglandinů.Recently (Folia pharmacol. Japanese. 88, 33-40, 77-84 and 205-213 (1986)), new esters of 1- (4-chlorobenzoyl) -5-methoxy-3-methylindole-3 have been introduced into clinical practice. -acetic acids with the anti-inflammatory activity of the free acid (drug indomethacin) but with a significantly lower ulcerogenic effect (1/7 to 1/10 indomethacin) in addition to a lesser inhibitory effect on prostaglandin biosynthesis.
Způsob výroby esterů arylalkanových kyselin s 1,2-diglyceridy obecného vzorce I podle vynálezu spočívá v tom, Že se na snadno dostupné substituované arylalkanové kyseliny obecného vzorce IIThe process for the preparation of the arylalkanoic acid esters of the 1,2-diglycerides of the formula I according to the invention consists in the conversion of readily available substituted arylalkanoic acids of the formula II
ArCHCOOH (II)ARCHCOOH (II)
R1 kde Ar a r' mají shora uvedený význam, ve formě halogenidů působí 1,2-diglyceridem obecného vzorce III!R 1 wherein Ar and r 'are as defined above, in the form of halides, acts with the 1,2-diglyceride of formula III;
RCOOyHjRCOOyHj
RCOOCH (III) ho<!:h2 kde R má shora uvedený význam, za míchání při teplotě reakční směsi 0 až 50 °C v prostředí terciárního aminu s výhodou pyridinu, triethylaminu, ethyldiisopropylaminu, popřípadě za přítomnosti katalytického množství 4-dimethylamino-, nebo 4-dibutylaminopyridinu po dobu 1 až 12 hodin. Průběh reakce RCOOCH (III), it <h 2 !: wherein R is as defined above, with stirring at an internal temperature of 0-50 ° C in an environment of a tertiary amine, preferably pyridine, triethylamine, ethyldiisopropylamine, optionally in the presence of a catalytic amount of 4-dimethylamino, or 4-dibutylaminopyridine for 1 to 12 hours. The course of the reaction
je možné sledovat'pomocí chromatografických metod, zvláště pomocí chromatografie na tenké vrstvě. Po ukončení reakce se reakční směs zředí vodou, případně po předchozím odpaření části rozpouštědla za sníženého tlaku, vodná fáze se extrahuje organickým rozpouštědlem jako dichlormethan, 1,2-dichlorethan nebo toluen, spojené organické podíly se promyjí zředěným roztokem minerální kyseliny, s výhodou kyseliny chlorovodíkové nebo sírové, vysuší a rozpouštědla se oddestilují za sníženého tlaku. Získá se ester obecného vzorce I.This can be monitored by chromatographic methods, in particular by thin-layer chromatography. After completion of the reaction, the reaction mixture is diluted with water, optionally after previously evaporating some of the solvent under reduced pressure, the aqueous phase is extracted with an organic solvent such as dichloromethane, 1,2-dichloroethane or toluene, and the combined organics are washed with a dilute mineral acid solution, preferably hydrochloric acid. or sulfuric acid, dried and the solvents distilled off under reduced pressure. An ester of formula I is obtained.
Vynález a jeho účinky jsou demonstrovány na několika příkladech.The invention and its effects are demonstrated in several examples.
Příklad 1Example 1
Směs 5,4 g kyseliny obecného vzorce II, kde Ar značí 4-isobutylfenyl, I? značí CHg,A mixture of 5.4 g of an acid of formula II wherein Ar is 4-isobutylphenyl; denotes CHg,
6,2 g thionylchloridu v 50 ml toluenu byla zahřívána 3 hodiny k varu, odpařena k suchu a zbytek byl rozpuštěn ve 20 ml pyridinu. Tento roztok byl během 30 minut přikapán za míchání k roztoku 10 g alkoholu vzorce III, kde R značí alkyl C15H31' ve 20 ml pyridinu při 0 °C. Pak byla směs míchána 6 hodin při 20 °C, rozložena ledovou vodou, promyta 3x 100 ml 1,2-dichlorethanu. Organický roztok byl promyt vodou, 5 % hmot. kyselinou sirovou, 5 % hmot. NaOH, vodou a vysušen bezvodým síranem hořečnatým. Po odpaření rozpouštědla byl zbytek přečištěn sloupcovou chromatografií. Bylo získáno 9,3 g (70 %) glyceridu obecného vzorce I, kde Ar,6.2 g of thionyl chloride in 50 ml of toluene were heated to boiling for 3 hours, evaporated to dryness and the residue was dissolved in 20 ml of pyridine. This solution was added dropwise with stirring to a solution of 10 g of the alcohol of formula III, wherein R is alkyl C 15 H 31 'in 20 ml pyridine at 0 ° C over 30 minutes. The mixture was stirred at 20 ° C for 6 hours, quenched with ice water, washed 3 times with 100 mL 1,2-dichloroethane. The organic solution was washed with water, 5 wt. % sulfuric acid, 5 wt. NaOH, water and dried over anhydrous magnesium sulfate. After evaporation of the solvent, the residue was purified by column chromatography. 9.3 g (70%) of a glyceride of the formula I were obtained, wherein Ar,
R1 a R mají výše uvedený význam, teploty tání 44 až 46 °C. NMR spektrum (CDClj, delta): 0,88 t (CH3), 1,26 s (CH2), 1,50 d (CH3), 1,63 m (CH2), 1,84 m (CH), 2,25 t (CH2), 2,30 t (CH2), 2,44 d (CH2), 3,70 q (CH), 4,08 m, 4,23 m, 4,30 m (CHp, 5,24 m (CH), 7,09 d a 7,18 d (jádro).R 1 and R are as defined above, melting point 44-46 ° C. NMR Spectrum (CDCl 3, δ): 0.88 t (CH 3 ), 1.26 s (CH 2 ), 1.50 d (CH 3 ), 1.63 m (CH 2 ), 1.84 m (CH) ), 2.25 t (CH 2 ), 2.30 t (CH 2 ), 2.44 d (CH 2 ), 3.70 q (CH), 4.08 m, 4.23 m, 4.30 m (CH p, 5.24 m (CH), 7.09 d and 7.18 d (nucleus)).
Příklad 2Example 2
Stejným způsobem jako v příkladu 1 bylo z 6,5 g kyseliny obecného vzorce II, kde Ar značí 2-fluor-4-bifenylyl, R1 = CH3, 6,2 g thionylchloridu v toluenu připraven odpovídající chlorid, který byl rozpuštěn ve 20 ml CH2C12· Roztok byl za míchání při 0 °C přikapán ke směsi 10 g alkoholu vzorce III, kde R značí uhlíkatý zbytek 4 g trlethylaminu, 0,1 gIn the same manner as in Example 1, 6.5 g of the acid of formula II wherein Ar is 2-fluoro-4-biphenylyl, R 1 = CH 3, 6.2 g of thionyl chloride in toluene, prepared the corresponding acid chloride which was dissolved in 20 ml CH 2 Cl 2 · The solution was added dropwise with stirring at 0 ° C to a mixture of 10 g of the alcohol of formula III, where R stands for a carbon residue 4 g of trlethylamine, 0.1 g
4-dimethylaminopyridinu a 30 ml CH2C12· Po 3 hodinách byla reakční směs rozložena vodou a zpracována jako v přikladu 1. Bylo získáno 9,1 g (65 %) esteru obecného vzorce I, kde Ar značí 2-fluor-4-bifenyl, R^ = CH3 a R = C^^Hj^, teploty tání 46 až 48 °C. NMR spektrum (CDC13, delta): 0,88 t (CHj) , 1,26 s (CH.,) , 1,54 d (CH3>, 1,60 m (CH2) , 2,25 m (CH2), 3,77 q (CH), 4,11 m, 4,21 m, 4,31 m (CHj), 5,28 m (CH), 7,10 až 7,55 m (jádro).4-dimethylaminopyridine and 30 ml of CH 2 Cl 2 · After 3 hours, the reaction was quenched with water and worked up as in Example 1. 9.1 g (65%) of the ester of formula I were obtained, where Ar is 2-fluoro-4- biphenyl, R ^ = CH 3 and R = C ^^^ Hj ^, mp 46-48 ° C. NMR Spectrum (CDCl 3 , δ): 0.88 t (CH 3 ), 1.26 s (CH 3 ), 1.54 d (CH 3 ), 1.60 m (CH 2 ), 2.25 m ( CH 2 ), 3.77 q (CH), 4.11 m, 4.21 m, 4.31 m (CH 3), 5.28 m (CH), 7.10 to 7.55 m (core).
Příklad 3Example 3
Stejným způsobem jako v přikladu 1 byl z 3,45 g kyseliny obecného vzorce II, kde Ar značí 6-methoxy-2-naftyl, F? = CH3, 2,7 g thionylchloridu v toluenu připraven chlorid, který byl rozpuštěn v CH2C12· Roztok byl za míchání při 0 °C přikapán ke směsi 6,21 g alkoholu vzorce III, kde R značí uhlíkatý zbytek olejové kyseliny, tj. ois-8-heptadecenyl, 2,5 g ethyldiisopropylaminu, 0,1 g 4-dimethylaminopyridinu v 50 ml dichlormethanu. Po 3 hodinách byla reakční směs zpracována jako v příkladu 1. Bylo získáno 5,7 g (68 %) esteru obecného vzorce I, kde Ar značí 6-methoxy-2-naftyl, R1 = CH3 a R značí uhlíkatý zbytek cis-8-heptadecenyl, jako olej. NMR spektrum (COClj, delta): 0,88 t (CHj), 1,26 s (CHj), 1,53 d (CHj), 1,58 m (CH2), 2,25 t (CH2) , 2,30 t (CH.,) , 3,75 q (CH) , 3,98 s (OCH3) , 4,10 m, 4,21 m, 4,30 m (CH2), 5,28 m (CH), 5,39 m (CH=CH), 7,08 až J,74 m (jádro).In the same manner as in Example 1, from 3.45 g of an acid of formula II wherein Ar is 6-methoxy-2-naphthyl, F? = CH 3 , 2.7 g of thionyl chloride in toluene prepared chloride which was dissolved in CH 2 Cl 2 · The solution was added dropwise with stirring at 0 ° C to a mixture of 6.21 g of an alcohol of formula III, where R is a carbonic oleic acid residue, i.e. ois-8-heptadecenyl, 2.5 g of ethyldiisopropylamine, 0.1 g of 4-dimethylaminopyridine in 50 ml of dichloromethane. After 3 hours, the reaction mixture was worked up as in Example 1. 5.7 g (68%) of the ester of formula I were obtained, wherein Ar is 6-methoxy-2-naphthyl, R 1 = CH 3 and R is the carbon residue of cis- 8-heptadecenyl, as an oil. Nuclear Magnetic Resonance Spectrum (COCl 3, delta): 0.88 t (CH 3 ), 1.26 s (CH 3 ), 1.53 d (CH 3 ), 1.58 m (CH 2 ), 2.25 t (CH 2 ), 2.30 t (CH.), 3.75 q (CH), 3.98 s (OCH 3 ), 4.10 m, 4.21 m, 4.30 m (CH 2 ), 5.28 m (CH), 5.39 m (CH = CH), 7.08 to J, 74 m (core).
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| CS876536A CS261332B1 (en) | 1987-09-10 | 1987-09-10 | Esters of arylalkane acids with 1,2-diglycerides and method of their production |
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| CS876536A CS261332B1 (en) | 1987-09-10 | 1987-09-10 | Esters of arylalkane acids with 1,2-diglycerides and method of their production |
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| CS876536A CS261332B1 (en) | 1987-09-10 | 1987-09-10 | Esters of arylalkane acids with 1,2-diglycerides and method of their production |
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