DK143600B - Analogifremgangsmaade til fremstilling af 1-substituerede 4-phenyl-2(1h)quinazolinonderivater - Google Patents
Analogifremgangsmaade til fremstilling af 1-substituerede 4-phenyl-2(1h)quinazolinonderivater Download PDFInfo
- Publication number
- DK143600B DK143600B DK445871A DK445871A DK143600B DK 143600 B DK143600 B DK 143600B DK 445871 A DK445871 A DK 445871A DK 445871 A DK445871 A DK 445871A DK 143600 B DK143600 B DK 143600B
- Authority
- DK
- Denmark
- Prior art keywords
- phenyl
- quinazolinone
- substituted
- derivatives
- trifluoroethyl
- Prior art date
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- 238000000034 method Methods 0.000 title description 7
- 238000002360 preparation method Methods 0.000 title description 3
- -1 1-substituted 4-phenyl-2 (1H) -quinazolinone Chemical class 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000006684 polyhaloalkyl group Polymers 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000002904 solvent Substances 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RJAMIBNUGBRPPO-UHFFFAOYSA-N 6-chloro-4-phenyl-1-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(Cl)=CC=C2N(CC(F)(F)F)C(=O)NC1C1=CC=CC=C1 RJAMIBNUGBRPPO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 229960002895 phenylbutazone Drugs 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- ZYEBURLARZGKSU-UHFFFAOYSA-N 1-(2,2-difluoroethyl)-6-nitro-4-phenylquinazolin-2-one Chemical compound C12=CC([N+](=O)[O-])=CC=C2N(CC(F)F)C(=O)N=C1C1=CC=CC=C1 ZYEBURLARZGKSU-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- JYLNVJYYQQXNEK-UHFFFAOYSA-N 3-amino-2-(4-chlorophenyl)-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(CN)C1=CC=C(Cl)C=C1 JYLNVJYYQQXNEK-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XXAVBCJCMSZFSW-UHFFFAOYSA-N 4-phenyl-1-(2,2,2-trifluoroethyl)-6-(trifluoromethyl)quinazolin-2-one Chemical compound N=1C(=O)N(CC(F)(F)F)C2=CC=C(C(F)(F)F)C=C2C=1C1=CC=CC=C1 XXAVBCJCMSZFSW-UHFFFAOYSA-N 0.000 description 1
- GDQTZFLLDBBUEQ-UHFFFAOYSA-N 4-phenyl-1-(2,2,2-trifluoroethyl)quinazolin-2-one Chemical compound N=1C(=O)N(CC(F)(F)F)C2=CC=CC=C2C=1C1=CC=CC=C1 GDQTZFLLDBBUEQ-UHFFFAOYSA-N 0.000 description 1
- YXCNXBIYPAICBQ-UHFFFAOYSA-N 6-chloro-4-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)quinazolin-2-one Chemical compound FC1=CC=CC=C1C1=NC(=O)N(CC(F)(F)F)C2=CC=C(Cl)C=C12 YXCNXBIYPAICBQ-UHFFFAOYSA-N 0.000 description 1
- OAIZNWQBWDHNIH-UHFFFAOYSA-N 6-chloro-4-phenyl-1-(2,2,2-trifluoroethyl)quinazolin-2-one Chemical compound N=1C(=O)N(CC(F)(F)F)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 OAIZNWQBWDHNIH-UHFFFAOYSA-N 0.000 description 1
- GZNZNLMQHVAGKM-UHFFFAOYSA-N 6-methoxy-1-(2,2,3,3,3-pentafluoropropyl)-4-phenylquinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)C(F)(F)F)C(=O)N=C1C1=CC=CC=C1 GZNZNLMQHVAGKM-UHFFFAOYSA-N 0.000 description 1
- MZGQIBQVSJDWHM-UHFFFAOYSA-N 6-methoxy-4-phenyl-1-(2,2,2-trifluoroethyl)quinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)F)C(=O)N=C1C1=CC=CC=C1 MZGQIBQVSJDWHM-UHFFFAOYSA-N 0.000 description 1
- YEQHOEQKTOHZEZ-UHFFFAOYSA-N 6-methyl-1-(2,2,3,3,3-pentafluoropropyl)-4-phenylquinazolin-2-one Chemical compound C12=CC(C)=CC=C2N(CC(F)(F)C(F)(F)F)C(=O)N=C1C1=CC=CC=C1 YEQHOEQKTOHZEZ-UHFFFAOYSA-N 0.000 description 1
- KREUPTNNOSLWMH-UHFFFAOYSA-N 6-nitro-4-phenyl-1-(2,2,2-trifluoroethyl)quinazolin-2-one Chemical compound C12=CC([N+](=O)[O-])=CC=C2N(CC(F)(F)F)C(=O)N=C1C1=CC=CC=C1 KREUPTNNOSLWMH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- SUBCHSYWLHCSLZ-UHFFFAOYSA-N FC(CN1C(N=C(C2=CC(=CC=C12)[N+](=O)[O-])C1=CC(=CC=C1)[N+](=O)[O-])=O)(F)F Chemical compound FC(CN1C(N=C(C2=CC(=CC=C12)[N+](=O)[O-])C1=CC(=CC=C1)[N+](=O)[O-])=O)(F)F SUBCHSYWLHCSLZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- SPAGIJMPHSUYSE-UHFFFAOYSA-N Magnesium peroxide Chemical compound [Mg+2].[O-][O-] SPAGIJMPHSUYSE-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 238000009835 boiling Methods 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
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
(db
I OT
(11) FREMLÆGGELSESSKRIFT 143600 (61) Tillæg til patent nr. 137647 DANMARK <»’» int ci.» c 07 d 239/82 ± (21) Ansøgning nr. 4458/71 (22) Indleveret den 10. Sep. 1971 f(24) Lebedag 10. Sep. 1971 (44) Ansøgningen fremlagt og fremlæggelsesskriftet offentliggjort den 14. 3Θρ. 1981
DIREKTORATET FOR
PATENT- OG VAREMÆRKEVÆSENET <3°) Prioritet begæret fra den
11. sep. 1970, 80173/70, JP
(41) Aim, tilg. 12. mar. 1972___________ (7i) SUMITOMO CHEMICAL COMPANY LIMITED, Osaka, JP.
(72) Opfinder: Shigeho Inaba, JP: Michihiro Yamamoto, JP: Kikuo Ishi= zumi, JP: Kazuo Mori, JP: Masao Koshiba, JP: Hisao Yamamoto, JP.
(74) Fuldmægtig under sagens behandling:
Ingeniørfirmaet Budde, Schou & Co._ (54) Analogifremgangsmåde til fremstilling af 1-substituerede 4-phenyl-2(1H)quinazolinonderivater.
Patent nr. 137.647 angår en analogifremgangsmåde til fremstilling af 1-substituerede 4-pheny1-2(IH)-quinazolinonderivater med den almene formel
HpCX° i hvilken R betyder polyhalogenalkyl med 2-3 carbonatomer og mindst 12 3 2 fluoratomer, og R , R og R hver især betyder hydrogen, alkyl med 1-4 carbonatomer, alkoxy med 1-4 carbonatomer, nitro, trifluor- 2 143600 methyl, alkylthio med 1-4 carbonatomer, alkylsulfonyl med 1-4 car-bonatomer eller halogen, og det ejendommelige ifølge hovedpatentet er, at et trihalogenacetamidobenzophenonderivat med formlen
R yK
N-CO-C-X
*iX Xx R i O-"*3 12 3 hvor R, R , R og R har den ovenfor anførte betydning, og X betyder halogen, omsættes med et ammoniumsalt i nærværelse af et opløsningsmiddel.
Den foreliggende opfindelse angår en anden analogifremgangsmåde til fremstilling af forbindelserne med formlen (I).
I forbindelserne med formlen (I) indbefatter halogenatomet chlor, brom, iod og fluor, C-^_^alkylgruppen betyder f.eks. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl og tert.butyl, C^_^-alkoxygruppen betyder f.eks. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy og tert.butoxy, C^_^alkylthiogruppen betyder f.eks. methylthio, ethylthio eller butylthio, og polyhalogenalkyl-gruppen betyder f.eks. difluormethyl, dichlormethyl, dibrommethyl, trifluormethyl, trichlormethyl, chlordifluormethyl og pentafluor-ethy1.
De ifølge opfindelsen fremstillede 1-substituerede 4-phenyl--2(IH)-quinazolinonderivater med formlen (I) har fremragende anti-inflammatorisk og analgetisk virkning med lav toksicitet over for pattedyr. Disse forbindelsers antiinflammatoriske virkning er kraftigere end virkningen af l,2-diphenyl-3,5-dioxo-4-n-butyl-pyrazolidin (phenylbutazon), og den akutte, subakutte og kroniske toksicitet er meget mindre end for phenylbutazon.
Fra beskrivelsen til dansk patent nr. 129.348 er det kendt, at visse 1-substituerede 4-phenylquinazolin-2-onderivater, der er nært beslægtet med de omhandlede 1-substituerede 4-phenyl-2-(1H)-quinazolinonderivater med formlen (I), har anti-inflamma-torisk virkning. Det har vist sig, at de 1-substituerede 4-phenyl--2(IH)-quinazolinonderivater med formlen (I) har en overraskende god anti-inflammatorisk virkning i forhold til de ovenfor omtalte 3 143600 kendte forbindelser, hvilket illustreres nærmere i det følgende.
De omhandlede forbindelsers anti-inflammatoriske virkning er endvidere bestemt ved hjælp af den hæmmende virkning på rotte-bagpoteødem fremkaldt ved injektion af 0,05 ral 1%'s carrageenin i steriliseret 0,9%'s natriumchloridopløsning.
Forsøgsforbindelserne indgives oralt 1 time inden carrageenin-injektionen. Til hver koncentrationsniveau anvendes 6 rotter.
Hos hver rotte måles poterumfanget som indikation for ødem-inhiberingen 3, 4 og 5 timer efter carrageenininjektionen, og gennemsnitsværdien for disse målinger beregnes for hver rotte. Den procentvise øderainhibering beregnes under anvendelse af formlen (1 - T/C) x 100, hvor T er gennemsnitsværdien for ødemrumfanget for den behandlede gruppe, og C er gennemsnitsværdien for ødemrumfanget for den ubehandlede kontrolgruppe. Forsøgsresultaterne er anført i nedenstående tabel.
Tabel
Dosis Inhibering af
Forbindelse_(rag/kg p.o.) ødera (%)_ 1-(2',2'-Difluorethyl)-4-phenyl-6- 20 41,2 -nitro-2(IH)-quinazolinon 50 61,8 1-(2',2',2'-Trifluorethyl)-4-phenyl- 50 44,4 -2 (IH)-quinazolinon 100 50,6 1-(2',2',2'-Trifluorethyl)-4-phenyl- 50 37,1 -6-chlor-2(IH)-quinazolinon 100 46,4 1-(2',2',2'-Trifluorethyl)-4-phenyl- 50 39,0 -6-methoxy-2(IH)-quinazolinon 100 51,0 1-(2',2',2'-Trifluorethyl)-4-phenyl- 50 48,2 -6-nitro-2(IH)-quinazolinon 100 53,1 1- (2',2',3',3'-Tetrafluorpropyl-4- 50 33,3 -phenyl-6-methoxy-2(IH)-quinazolinon 100 53,1 1-(2',2',2'-Trifluorethyl)-4-phenyl-6- 100 29,7 -chlor-3,4-dihydro-2(IH)-quinazolinon 200 46,3 (kendt fra beskrivelsen til tilgængelig ans. nr. 3328/71, der har ført til patent nr. 129.348) 4 143600
Fremgangsmåden ifølge den foreliggende opfindelse er ejendommelig ved, at en forbindelse med formlen (Ila) eller (Ilb)
Rf*TT (IIa) R1
R
f R2 1<:Τ (Ilb) R1
R
12 3 hvor R , R , R og R har den ovenfor anførte betydning bringes i kontakt med et oxidationsmiddel.
Egnede oxidationsmidler er f.eks. alkalimetalpermanganat, såsom natriumpermanganat og kaliumpermanganat, mangandioxid, magnesium-dioxid, alkalimetalferricyanid såsom kaliumferricyanid og mercuriace-tat.
Omsætningen kan fortrinsvis udføres i nærværelse af et opløsningsmiddel eller en opløsningsmiddelblanding. Valget af opløsningsmiddel afhænger af det anvendte oxidationsmiddel, og opløsningsmidlet vælges blandt benzen, toluen, ether, tetrahydrofuran, dioxan, acetone, vand, ethanol, isopropanol og dimethylsulfoxid.
Omsætningen gennemføres sædvanligvis ved en temperatur i området fra ca. stuetemperatur op til kogepunktet for det anvendte opløsningsmiddel.
Fremgangsmåden ifølge opfindelsen forklares nærmere i de følgende eksempler, der illustrerer foretrukne udførelsesformer.
5 143600
Eksempel 1.
Til en opløsning af 7,77 g l-(2,2,2-trifluorethyl)-4-phenyl--6-chlor-3,4-dihydro-2(IH)-quinazolinon i 100 ml dioxan sættes dråbevis en suspension af 3,6 g kaliumpermanganat i 30 ml vand ved 20-30°C. Blandingen omrøres derpå i stuetemperatur i 3 timer.
Til den fremkomne blanding sættes 1 g myresyre, og omrøringen fortsættes. Det dannede brune bundfald frafiltreres og vaskes med 30 ml dioxan. Filtratet og vaskevæskerne kombineres og koncentreres under formindsket tryk. Remanensen opløses i 50 ml chloroform, og chloroformopløsningen vaskes med vand og tørres over vandfri natriumsulfat.
Opløsningsmidlet fjernes under formindsket tryk, og remanensen omkrystalliseres fra isopropylalkohol, hvorved fås 6,95 g 1-(2,-2,2-trifluorethyl)-4-phenyl-6-chlor-2(IH)-quinazolinon med smp. 185-186°C.
Eksempel 2.
Analogt med den i eksempel 1 beskrevne fremgangsmåde fremstilles følgende forbindelser: 1-(2,2,2-trifluorethyl)-4-phenyl-2(IH)-quinazolinon, smp. 181-182°C, 1-(2,2,2-trifluorethyl)-4-phenyl-6-nitro-2(IH)-quinazolinon, smp. 207-208°C, 1-(2,2,2-trifluorethyl)-4-phenyl-6-methoxy-2(IH)-quinazolinon, smp. 157-158°C, 1-(2,2,2-trifluorethyl)-4-phenyl-6-trifluormethyl-2(IH)-quinazolinon, smp. 173-174°C, 1-(2,2,2-trifluorethyl)-4-(o-fluorphenyl)-6-chlor-2(IH)-quinazolinon, smp. 194,5-195,5°C, 1-(2,2,2-trifluorethyl)-4-(m-nitrophenyl)-6-nitro-2(IH)-quinazolinon, smp. 205-206°C, 1-(2,2-difluorethyl)-4-phenyl-6-nitro-2(IH)-quinazolinon, smp.
197-197,5°C, 1-(2,2,3,3-tetrafluorpropyl)-4-phenyl-6-methoxy-2(IH)-quinazolinon smp. 151-152°C, 1-(2,2,3,3,3-pentafluorpropyl)-4-phenyl-6-methyl-2(IH)-quinazolinon, smp. 175-176°C, og 1-(2,2,3,3,3-pentafluorpropyl)-4-phenyl-6-methoxy-2(IH)-quinazolinon, smp. 135-136°C.
6 143600
Eksempel 3.
Analogt med den i eksempel 1 beskrevne fremgangsmåde, idet der dog i stedet for 1-(2,2,2-trifluorethyl)-4-phenyl-6-chlor-3,4--dihydro-2(IH)-quinazolinon anvendes l-(2,2,2-trifluorethyl)-4-phen-yl-6-chlor-l,2-dihydroquinazolin, fremstilles 1-(2,2,2-trifluorethyl) -4-phenyl-6-chlor-2 (IH) -quinazolinon med smp. 185-186°C,
Claims (1)
143600 7 Patentkrav . Analogifremgangsmåde til fremstilling af de i patent nr. 137.647 omhandlede 1-substituerede 4-phenyl-2(IH)-quinazolinon-derivater med formlen . 9"' R (i) fcxiL. R1 R 12 3 hvor R , R og R hver især betyder hydrogen, halogen, C^_4 alkyl, alkoxy, nitro, trifluormethyl, alkylthio eller al- kylsulfonyl, R betyder en polyhalogenalkylgruppe med 2-3 carbon-atomer og mindst 2 fluoratomer, kendetegnet ved, at en forbindelse med formlen (Ila) eller (Ilb) 4--R3 R2 I (Ha) R1 R •i'*'"''! Γ i—R r2 γ dib) R1 I R 12 3 hvor R , R , R og R har den ovenfor anførte betydning, bringes i kontakt med et oxidationsmiddel.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8017370 | 1970-09-11 | ||
| JP8017370 | 1970-09-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK143600B true DK143600B (da) | 1981-09-14 |
| DK143600C DK143600C (da) | 1982-02-15 |
Family
ID=13710930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK445871A DK143600C (da) | 1970-09-11 | 1971-09-10 | Analogifremgangsmaade til fremstilling af 1-substituerede 4-phenyl-2(1h)quinazolinonderivater |
Country Status (8)
| Country | Link |
|---|---|
| AT (1) | AT311360B (da) |
| CA (1) | CA949570A (da) |
| CH (1) | CH557355A (da) |
| DK (1) | DK143600C (da) |
| FI (1) | FI59798C (da) |
| HU (1) | HU162335B (da) |
| NL (1) | NL170954C (da) |
| SU (1) | SU435614A3 (da) |
-
1971
- 1971-09-08 AT AT781671A patent/AT311360B/de not_active IP Right Cessation
- 1971-09-08 FI FI251271A patent/FI59798C/fi active
- 1971-09-08 CH CH1317871A patent/CH557355A/de not_active IP Right Cessation
- 1971-09-08 HU HUSU000671 patent/HU162335B/hu unknown
- 1971-09-09 SU SU1699018A patent/SU435614A3/ru active
- 1971-09-10 CA CA122,570A patent/CA949570A/en not_active Expired
- 1971-09-10 DK DK445871A patent/DK143600C/da not_active IP Right Cessation
- 1971-09-10 NL NL7112458A patent/NL170954C/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HU162335B (da) | 1973-01-29 |
| FI59798C (fi) | 1981-10-12 |
| CA949570A (en) | 1974-06-18 |
| CH557355A (de) | 1974-12-31 |
| NL170954B (nl) | 1982-08-16 |
| FI59798B (fi) | 1981-06-30 |
| NL170954C (nl) | 1983-01-17 |
| AT311360B (de) | 1973-11-12 |
| SU435614A3 (ru) | 1974-07-05 |
| DK143600C (da) | 1982-02-15 |
| NL7112458A (da) | 1972-03-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |