NO771722L - PROCEDURES FOR THE PREPARATION OF THERAPEUTIC ACTIVE BENZOPYRANE COMPOUNDS - Google Patents
PROCEDURES FOR THE PREPARATION OF THERAPEUTIC ACTIVE BENZOPYRANE COMPOUNDSInfo
- Publication number
- NO771722L NO771722L NO771722A NO771722A NO771722L NO 771722 L NO771722 L NO 771722L NO 771722 A NO771722 A NO 771722A NO 771722 A NO771722 A NO 771722A NO 771722 L NO771722 L NO 771722L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- alkyl
- compound
- hydrogen
- derivative
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 13
- 150000001562 benzopyrans Chemical class 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title description 2
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 229910052783 alkali metal Chemical group 0.000 claims description 3
- 150000001340 alkali metals Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- HBBZNIVGQORKNC-UHFFFAOYSA-N 6,8-diethyl-5-hydroxy-4-oxochromene-2-carboxylic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C(O)C(CC)=CC(CC)=C21 HBBZNIVGQORKNC-UHFFFAOYSA-N 0.000 claims 1
- CJTURQGHQPDNDA-UHFFFAOYSA-N 6,8-ditert-butyl-4-oxochromene-2-carboxylic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=CC(C(C)(C)C)=CC(C(C)(C)C)=C21 CJTURQGHQPDNDA-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- -1 alkaline earth metal salts Chemical class 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- VFFTVZUIDYJUQS-UHFFFAOYSA-N 5-hydroxy-4-oxo-10-propyl-6,7,8,9-tetrahydrobenzo[g]chromene-2-carboxylic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1CCCCC1=C2O VFFTVZUIDYJUQS-UHFFFAOYSA-N 0.000 description 1
- VJRXKKYEAJRAQL-UHFFFAOYSA-N 6,8-ditert-butyl-4-oxochromene-2-carboxamide Chemical compound O1C(C(N)=O)=CC(=O)C2=CC(C(C)(C)C)=CC(C(C)(C)C)=C21 VJRXKKYEAJRAQL-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940116731 Uricosuric agent Drugs 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940066769 systemic antihistamines substituted alkylamines Drugs 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 239000003383 uricosuric agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Foreliggende oppfinnelse vedrører en ny fremgangsmåte til fremstilling av benzopyranforbindelser, samt nye mellom-produkter. The present invention relates to a new method for the production of benzopyran compounds, as well as new intermediate products.
Oppfinnelsen angår mer spesielt fremstilling av forbindelser med den generelle formel: hvor R,., Rg, R^og Rg er valgt fra hydrogen, hydroksy, alkyl, eller et tilstøtende par av Rj-, R^, R^og Rg sammen danner en -(CH2)4-kjede, samt farmasøytisk akseptable derivater derav, og denne fremgangsmåte er kjennetegnet ved.at man ringslutter en forbindelse med formelen: The invention relates more particularly to the preparation of compounds of the general formula: where R,., Rg, R^ and Rg are selected from hydrogen, hydroxy, alkyl, or an adjacent pair of Rj-, R^, R^ and Rg together form a -(CH2)4 chain, as well as pharmaceutically acceptable derivatives thereof, and this method is characterized by ring-closing a compound with the formula:
eller et egnet derivat derav, hvor Rc, R,., R_, og R„ har den or a suitable derivative thereof, wherein Rc, R,., R_, and R„ have it
Db/ oDb/ o
ovenfor angitte betydning, og L^, som kan være like eller forskjellige, er hver hydrogen, aryl eller alkyl, eller danner sammen en mettet eller umettet alkylenkjede, og M er hydrogen eller et alkali-metall. meaning above, and L^, which may be the same or different, are each hydrogen, aryl or alkyl, or together form a saturated or unsaturated alkylene chain, and M is hydrogen or an alkali metal.
Ringslutningen kan utføres ved oppvarming underThe loop closure can be carried out by heating below
basiske eller nøytrale betingelser. Det er imidlertid foretrukket å utføre ringslutningen i nærvær av en syre, f.eks. saltsyre, og i et oppløsningsmiddel som er inert under reaksjonsbetingelsene, f.eks. en lavere alkanol slik som etanol. Reaksjonen kan utføres ved fra ca. 20 til 150 C. Reaksjonen kan hensiktsmessig utføres når derivatet av -COOH-gruppen er en gruppe -CONL^L^hvor og har den ovenfor angitte betydning. Det er foretrukket at L, og er hydrogen, fenyl, alkyl Cl-6 eller sammen danner en 4- eller 5-ledet alkylenkjede, f. eks. danner en piperidinring sammen med nitrogenatomet. basic or neutral conditions. However, it is preferred to carry out the ring closure in the presence of an acid, e.g. hydrochloric acid, and in a solvent which is inert under the reaction conditions, e.g. a lower alkanol such as ethanol. The reaction can be carried out at from approx. 20 to 150 C. The reaction can conveniently be carried out when the derivative of the -COOH group is a group -CONL^L^where and has the above meaning. It is preferred that L, and is hydrogen, phenyl, alkyl Cl-6 or together form a 4- or 5-membered alkylene chain, e.g. forms a piperidine ring together with the nitrogen atom.
Forbindelser med formel II, kan fremstilles ved omsetning av en forbindelse med formel I med et amin, HNL^L^, f.eks. ved en forhøyet temperatur og i et oppløsningsmiddel som er inert under reaksjonsbetingelsene, slik som etanol, Compounds of formula II can be prepared by reacting a compound of formula I with an amine, HNL^L^, e.g. at an elevated temperature and in a solvent that is inert under the reaction conditions, such as ethanol,
eller ved omsetning av en forbindelse med formelen:or by reacting a compound with the formula:
hvor Rc, R-, R.., RQ og M har den ovenfor angitte betydning, med where Rc, R-, R.., RQ and M have the meaning stated above, med
b b / ob b / o
en forbindelse med formelen:a compound with the formula:
eller et acetal derav, hvor L, og L_ har den overnfor angitte betydning. Denne sistnevnte reaksjon kan utføres ved en temperatur på fra ca. 20° til 100°C, og fortrinnsvis i et oppløsnings-middel som er inert under reaksjonsbetingelsene, f.eks. en lavere alkanol slik som etanol. Når en av L, og L2er hydrogen kan forbindelsen med formel II eksistere i den tautomere form av forbindelsen med formelen: or an acetal thereof, where L, and L_ have the meaning indicated above. This latter reaction can be carried out at a temperature of from approx. 20° to 100°C, and preferably in a solvent which is inert under the reaction conditions, e.g. a lower alkanol such as ethanol. When one of L, and L2 is hydrogen, the compound of formula II can exist in the tautomeric form of the compound of formula:
eller et egnet derivat derav, hvor M og har den ovenfor angitte betydning. or a suitable derivative thereof, where M and have the above meaning.
Alternativt kan forbindelser med formel II fremstilles ved omsetning av en forbindelse med formelen: Alternatively, compounds of formula II can be prepared by reacting a compound of the formula:
hvor R er en alkylgruppe og i Hal er klor eller brom, med en forbindelse med formelen: eller et egnet derivat derav, dealkylering av den resulterende forbindelse med formelen: eller et egnet derivat derav, hvor R^., Rg, R^og Rg og M har den ovenfor angitte betydning, for oppnåelse av en forbindelse med formelen: wherein R is an alkyl group and in Hal is chlorine or bromine, with a compound of the formula: or a suitable derivative thereof, dealkylation of the resulting compound of the formula: or a suitable derivative thereof, wherein R^, Rg, R^ and Rg and M has the meaning given above, to obtain a compound of the formula:
eller et egnet derivat derav, hvor R^, Rg, R^og Rg og M har den ovenfor angitte betydning, og deretter i omsetning av forbindelsen med formel XI med en forbindelse med formelen HNL^I^hvor og har den ovenfor angitte betydning. or a suitable derivative thereof, where R^, Rg, R^ and Rg and M have the above-mentioned meaning, and then in reaction of the compound of formula XI with a compound of the formula HNL^I^where and has the above-mentioned meaning.
Forbindelsene med formel V, VIII samt forbindelsen med formel VI og IX er enten kjente eller kan fremstilles fra kjente forbindelser under anvendelse av konvensjonell teknikk. The compounds of formula V, VIII as well as the compound of formula VI and IX are either known or can be prepared from known compounds using conventional techniques.
Passende derivater av -COOH-gruppen i forbindelsene med formelene VII, IX, X og XI omfatter alkylesterene derav og Suitable derivatives of the -COOH group in the compounds of formulas VII, IX, X and XI include the alkyl esters thereof and
-NL^l^-amidene derav.-NL^l^-amides thereof.
Forbindelsene med formel I (og særlig forbindelsen i eksemplene 1 og 3) er nyttige ved behandling av tilstander hvori antigen/antistoff-reaksjoner finner sted, f.eks. allergisk astma. Forbindelsen med formelen I hvori R^og R^begge er hydrogen og Rg og Rg begge er t-butyl, samt farmasøytisk akseptable derivater derav, er også nyttige som uricosuriske midler. The compounds of formula I (and particularly the compound in examples 1 and 3) are useful in the treatment of conditions in which antigen/antibody reactions take place, e.g. allergic asthma. The compound of formula I wherein R₁ and R₂ are both hydrogen and Rg and Rg are both t-butyl, as well as pharmaceutically acceptable derivatives thereof, are also useful as uricosuric agents.
Farmasøytisk akseptable derivater av forbindelsenePharmaceutically acceptable derivatives of the compounds
med formel I omfatter farmasøytisk akseptable salter, estereof formula I include pharmaceutically acceptable salts, esters
og amider av 2- karboksylsyre-gruppen. Egnede salter er ammonium-, og alkalimetall - (f.eks. natrium, kalium og litium) and amides of the 2-carboxylic acid group. Suitable salts are ammonium and alkali metal - (e.g. sodium, potassium and lithium)
og jordalkalimetallsalter (f.eks. kalsium eller magnesium),and alkaline earth metal salts (e.g. calcium or magnesium),
og salter med egnede organiske baser, f.eks. salter med lavere alkylaminer slik som i metylamin eller,etylamin, med substi-tuerte lavere alkylaminer, f.eks. hydroksysubstituerte alkylaminer eller med enkle monocykliske nitrogenheterocykliske. forbindelser, f.eks. piperidin eller morfolin. Egnede estere er enkle lavere alkylestere, estere avledet fra alkoholer inneholdende basiske grupper, f.eks. di-lavere-alkylaminosubstituerte alkanoler, og acyloksyalkylestere, f.eks. en lavere acyl-lavere alkylester, eller en bis-ester avledet fra en di-hydroksyforbind-else, f.eks. en di (hydroksy-lavere alkyDeter. De farma- and salts with suitable organic bases, e.g. salts with lower alkylamines such as in methylamine or ethylamine, with substituted lower alkylamines, e.g. hydroxy-substituted alkylamines or with simple monocyclic nitrogen heterocyclics. compounds, e.g. piperidine or morpholine. Suitable esters are simple lower alkyl esters, esters derived from alcohols containing basic groups, e.g. di-lower-alkylamino-substituted alkanols, and acyloxyalkyl esters, e.g. a lower acyl lower alkyl ester, or a bis ester derived from a dihydroxy compound, e.g. a di (hydroxy-lower alkylDeter. The pharma-
søytisk akseptable saltene av basiske estere, f.eks. cytically acceptable salts of basic esters, e.g.
hydrokloride, kan også anvendes. Esterene kan fremstilles på konvensjonell måte, f.eks. ved forestering, transfor-estering eller omsetning med syren eller et salt derav med en passende forbindelse inneholdende en avspaltningsgruppe. hydrochloride, can also be used. The esters can be prepared in a conventional manner, e.g. by esterification, transesterification or reaction with the acid or a salt thereof with a suitable compound containing a leaving group.
Som amider kan nevnes det enkle amid avledet fra ammoniakkAs amides, the simple amide derived from ammonia can be mentioned
og amider avledet fra mono- eller di-alkyl C 1-6 aminer.and amides derived from mono- or di-alkyl C 1-6 amines.
I forbindelser med formel I er det foretrukket atIn compounds of formula I, it is preferred that
R,, er hydrogen eller hydroksy, Rg er alkyl og R^ er hydrogen eller Rg og R^sammen danner en -( CU^)^-kjede, og Rg er alkyl. Når en eller flere av R,-, Rg, R^ og Rg er alkyl er det foretrukket at de er alkyl C 1-4, og spesielt propyl eller botyl. R,, is hydrogen or hydroxy, Rg is alkyl and R^ is hydrogen or Rg and R^ together form a -(CU^)^ chain, and Rg is alkyl. When one or more of R1-, Rg, R1 and Rg are alkyl, it is preferred that they are alkyl C 1-4, and especially propyl or butyl.
Oppfinnelsen illustreres ytterligere ved hjelp avThe invention is further illustrated by means of
de nednestående eksempler, hvor delangivelsene er vektdeler. the examples below, where the parts are parts by weight.
EksemplerExamples
1. 6, 8- di- t- butyl- 4- okso- 4H- l- benzopyran- 2- karboksamid1. 6, 8- di- t- butyl- 4- oxo- 4H- l- benzopyran- 2- carboxamide
En oppløsning av 2-amino-3-(3,5-di-t-butyl-2-hydroksy-benzoyl)akrylamid (1,1 g) i etanol (100 ml) blir mettet med hydrogenklorid. Den resulterende blanding ble hensatt ved rom-temperatur i en time. Tilsétning av eter ga et hvitt bunn-fall som ble frafiltrert, vasket med eter og tørket hvilket ga den ovenstående ønskede forbindelse, smp-255-257°C. 2 . 6 , 8- dietyl- 5- hydroksy- 4- okso- 4H-^ l- benzopyran- 2- karboksylsyre En oppløsning av 2-fenylamino-3(3,5-diety1-2,6-dihydroksy-benzoyl)-akrylsyre (2 g) i etanol (100 ml), ble mettet med hydrogenklorid. Den resulterende blanding ble hensatt ved rom-temperatur i 1 time. Fjerning av etanol i vakuum ga en olje som ble krystallisert fra eddiksyre hvilket ga,den ovenstående ønskede forbindelse, smp. 220-221°C. 3.. 6, 7, 8, 9- tetrahydro- 5- hydroksy- 4- okso- 10- n- propyl- 4H- nafto ( 2, 3- b) pyran- 2- karboksylsyre A solution of 2-amino-3-(3,5-di-t-butyl-2-hydroxy-benzoyl)acrylamide (1.1 g) in ethanol (100 ml) is saturated with hydrogen chloride. The resulting mixture was left at room temperature for one hour. Addition of ether gave a white precipitate which was filtered off, washed with ether and dried to give the above desired compound, mp-255-257°C. 2. 6 , 8- diethyl- 5- hydroxy- 4- oxo- 4H-^ l- benzopyran- 2- carboxylic acid A solution of 2-phenylamino-3(3,5-diethy1-2,6-dihydroxy-benzoyl)-acrylic acid ( 2 g) in ethanol (100 ml), was saturated with hydrogen chloride. The resulting mixture was left at room temperature for 1 hour. Removal of ethanol in vacuo gave an oil which crystallized from acetic acid to give the above desired compound, m.p. 220-221°C. 3.. 6, 7, 8, 9- tetrahydro- 5- hydroxy- 4- oxo- 10- n- propyl- 4H- naphtho ( 2, 3- b) pyran- 2- carboxylic acid
Behandling av 2-piperidino-3-(4,5,6,7-tetrahydro-2,8-dihydroksy-4-n-propylnaftoyl)- akrylsyre med hydrogenklorid i etanol som i eksempel 2, ga etter krystallisering fra aceton den ovenstående ønskede forbindelse, smp. 23 0-/ 23 2 oC. Treatment of 2-piperidino-3-(4,5,6,7-tetrahydro-2,8-dihydroxy-4-n-propylnaphthoyl)-acrylic acid with hydrogen chloride in ethanol as in Example 2 gave, after crystallization from acetone, the above desired compound, m.p. 23 0-/ 23 2 oC.
Claims (10)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2057176 | 1976-05-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO771722L true NO771722L (en) | 1977-11-22 |
Family
ID=10148114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO771722A NO771722L (en) | 1976-05-19 | 1977-05-16 | PROCEDURES FOR THE PREPARATION OF THERAPEUTIC ACTIVE BENZOPYRANE COMPOUNDS |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS52142073A (en) |
| DK (1) | DK208877A (en) |
| FI (1) | FI771545A (en) |
| NO (1) | NO771722L (en) |
| PT (1) | PT66569B (en) |
| SE (1) | SE7705849L (en) |
-
1977
- 1977-05-12 DK DK208877A patent/DK208877A/en unknown
- 1977-05-16 FI FI771545A patent/FI771545A/fi not_active Application Discontinuation
- 1977-05-16 NO NO771722A patent/NO771722L/en unknown
- 1977-05-17 SE SE7705849A patent/SE7705849L/en unknown
- 1977-05-17 JP JP5605177A patent/JPS52142073A/en active Pending
- 1977-05-18 PT PT66569A patent/PT66569B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT66569B (en) | 1979-04-13 |
| DK208877A (en) | 1977-11-20 |
| SE7705849L (en) | 1977-11-20 |
| PT66569A (en) | 1977-06-01 |
| FI771545A (en) | 1977-11-20 |
| JPS52142073A (en) | 1977-11-26 |
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