DK141064B - Fremgangsmåde til fremstilling af 3,4-dihydro-2(1H)-quinazolinonderivater. - Google Patents
Fremgangsmåde til fremstilling af 3,4-dihydro-2(1H)-quinazolinonderivater. Download PDFInfo
- Publication number
- DK141064B DK141064B DK22277AA DK22277A DK141064B DK 141064 B DK141064 B DK 141064B DK 22277A A DK22277A A DK 22277AA DK 22277 A DK22277 A DK 22277A DK 141064 B DK141064 B DK 141064B
- Authority
- DK
- Denmark
- Prior art keywords
- dihydro
- formula
- quinazolinone
- compounds
- phenyl
- Prior art date
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- 238000000034 method Methods 0.000 title description 10
- CTOUNZIAEBIWAW-UHFFFAOYSA-N 3,4-dihydro-1h-quinazolin-2-one Chemical class C1=CC=C2NC(=O)NCC2=C1 CTOUNZIAEBIWAW-UHFFFAOYSA-N 0.000 title description 5
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 description 15
- -1 methylene-dioxy Chemical group 0.000 description 14
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- IKFJYSLTRULFPV-UHFFFAOYSA-N 1-(2,2-difluoroethyl)-6-methoxy-4-phenyl-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)F)C(=O)NC1C1=CC=CC=C1 IKFJYSLTRULFPV-UHFFFAOYSA-N 0.000 description 1
- GQTYRBUHGKFRPM-UHFFFAOYSA-N 1-(2-chloro-2,2-difluoroethyl)-6-methoxy-4-phenyl-3,4-dihydroquinazolin-2-one Chemical compound ClC(CN1C(NC(C2=CC(=CC=C12)OC)C1=CC=CC=C1)=O)(F)F GQTYRBUHGKFRPM-UHFFFAOYSA-N 0.000 description 1
- VTPBKOLWXHMSNG-UHFFFAOYSA-N 1-(4-methoxyphenyl)-1-(2,2,2-trifluoroethyl)urea Chemical compound COC1=CC=C(N(CC(F)(F)F)C(N)=O)C=C1 VTPBKOLWXHMSNG-UHFFFAOYSA-N 0.000 description 1
- IBSQPLPBRSHTTG-UHFFFAOYSA-N 1-chloro-2-methylbenzene Chemical compound CC1=CC=CC=C1Cl IBSQPLPBRSHTTG-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
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- 125000004780 2-chloro-2,2-difluoroethyl group Chemical group [H]C([H])(*)C(F)(F)Cl 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- STCLQQPKVUQPRY-UHFFFAOYSA-N 6-methoxy-1-(2,2,3,3,3-pentafluoropropyl)-4-phenyl-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)C(F)(F)F)C(=O)NC1C1=CC=CC=C1 STCLQQPKVUQPRY-UHFFFAOYSA-N 0.000 description 1
- KBZITYIDKPBARR-UHFFFAOYSA-N 6-methoxy-4-phenyl-1-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)F)C(=O)NC1C1=CC=CC=C1 KBZITYIDKPBARR-UHFFFAOYSA-N 0.000 description 1
- OAKRAIGHJUMJMH-UHFFFAOYSA-N 6-methoxy-4-phenyl-1-(2,2,2-trifluoroethyl)-3,4-dihydroquinazoline-2-thione Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)F)C(=S)NC1C1=CC=CC=C1 OAKRAIGHJUMJMH-UHFFFAOYSA-N 0.000 description 1
- KJMMGLIWDINDIJ-UHFFFAOYSA-N 6-methoxy-4-phenyl-1-(2,2,3,3-tetrafluoropropyl)-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)C(F)F)C(=O)NC1C1=CC=CC=C1 KJMMGLIWDINDIJ-UHFFFAOYSA-N 0.000 description 1
- QSCWVGPKFAZOMA-UHFFFAOYSA-N 6-methoxy-4-thiophen-2-yl-1-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(OC)=CC=C2N(CC(F)(F)F)C(=O)NC1C1=CC=CS1 QSCWVGPKFAZOMA-UHFFFAOYSA-N 0.000 description 1
- VOORLLWLXQZWGI-UHFFFAOYSA-N 6-methyl-1-(2,2,3,3,3-pentafluoropropyl)-4-phenyl-3,4-dihydroquinazolin-2-one Chemical compound C12=CC(C)=CC=C2N(CC(F)(F)C(F)(F)F)C(=O)NC1C1=CC=CC=C1 VOORLLWLXQZWGI-UHFFFAOYSA-N 0.000 description 1
- PEPDGNSLDHYFNX-UHFFFAOYSA-N 8-phenyl-5-(2,2,2-trifluoroethyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]quinazolin-6-one Chemical compound C12=CC=3OCOC=3C=C2N(CC(F)(F)F)C(=O)NC1C1=CC=CC=C1 PEPDGNSLDHYFNX-UHFFFAOYSA-N 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
- HCHKCACWOHOZIP-IGMARMGPSA-N Zinc-65 Chemical compound [65Zn] HCHKCACWOHOZIP-IGMARMGPSA-N 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 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
- 125000004708 n-butylthio group Chemical group C(CCC)S* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229940102001 zinc bromide Drugs 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pain & Pain Management (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
(ΐιί^) (ID FREMLÆGGELSESSKRIFT 1 i+1 06 *+ nAMRJIAD/ (51) Int.CI.3 C 07 0 239/78 // C 07 D 409/04 UAI\lmAni\ c 07 D 491/94 §(21) Arowgnlng nr. 222/V (22) Indleverat den 20. jan. I977 (23) Ubedag 20. jan. 1977 (44) Aneagnlngen fremlagt og fremleggeleeeekrlftet offentliggjort den 7« jan. 1980 DIREKTORATET FOR ^ ^ PATENT-OG VAREMÆRKEVÆSENET <30) Prioritet begaerat fra den
23. jan. 1976, ¢920/76, JP
OD SUMITOMO CHEMICAL COMPANY LIMITED, 15, Kltahama-5~chome, Higaehl-ku,
Osaka, JP.
(72) Opfinder: Mlohlhlro Yamamoto, 16-40-309, Takagihlgashl-raachi, Nishi-nomiya-shl, JP: Shigénari Katayama, 14-7, Mefu-2-chome, Taksrazuka-shi, JP: Masao Koshiba, 4-1-1057 Ryadocho, Nishinomlya-shi, JP: Hleao Yamamoto, 4-33, Morlkltacho-6-chome, Higashinada-ku, Kot)©, JP.
(74) Fuldmaagtlg under aagena behandling:
Ingeniørfirmaet Budde, Schou & Co.
....... .............. """"' ....... 'JJI....... -- ' —- (54) Fremgangsmåde til fremstilling af 3,4-dlhydro-2(1H) -quinazolinonderi-vater.
Den foreliggende opfindelse angår en sårlig fremgangsmåde til fremstilling af 3,4-dihydro-2(IH)-quinazolinonderivater med formlen 1 r4 ΪΓ f IT i (i) R^ 1 2 hvor R og R hver isar betyder hydrogen, lavere alkyl, lavere alkyl- 1 2 thio eller lavere alkoxy, eller RA og R kan tilsammen betyde methylen- - 2 - 141064 3 4 dioxy, R betyder polyhalogen-lavere alkyl, R betyder phenyl, halogen- phenyl, lavere alkoxyphenyl, lavere alkylphenyl eller thienyl, og X betyder oxygen eller svovl, ved hvilken en forbindelse med formlen R1 Γ2 I (II) R2 |3
R
12 3 hvor R , R , R og X har de ovennævnte betydninger, omsættes med en forbindelse med formlen R4·-CHO (III) 4 hvor R har den ovennævnte betydning, under opvarmning i nærværelse af en katalysatorf eventuelt i et indifferent opløsningsmiddel, og fremgangsmåden ifølge opfindelsen er ejendommelig ved, at der som katalysator anvendes et zinkhalogenid.
Ved udtrykket lavere alkyl skal her forstås alkyl med 1-4 carbonatomer, f.eks. methyl, ethyl, n-propyl, isopropyl, n-butyl eller isobutyl, ved lavere alkoxy skal forstås alkoxy med 1-4 carbonatomer, f.eks. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy eller isobutoxy, ved lavere alkylthio skal forstås alkylthio med 1-4 carbonatomer, f.eks. methylthio, ethylthio, n-propylthio, isopropylthio eller n-butylthio, ved polyhalogen-lavere alkyl forstås eksempelvis 2,2-difluorethyl, 2-chlor-2,2-difluorethyl, 2,2,2-trifluorethyl, 2,2,3,3-tetrafluorpropyl og 2,2,3,3,3-penta-fluorpropyl, ved halogenphenyl kan forstås o-fluorphenyl, p-fluor-phenyl, o-chlorphenyl, m-chlorphenyl eller p-chlorphenyl, og ved lavere alkylphenyl eller lavere alkoxyphenyl forstås o-, m-eller p-lavere alkyl- eller alkoxy-substitueret phenyl.
3,4-Dihydro-2(IH)-quinazolinonderivaterne med formlen (I) er kendte forbindelser med anti-inflammatoriske og analgetiske virkninger, og de er meget anvendelige mellemprodukter ved fremstillingen af anti-inflammatoriske og analgetiske midler med 4
formlen R
‘‘rr^i -
R2 I 3 X
R
“ 3 " 14106Λ 12 3 4 hvor R , R , R , R og X har de ovennævnte betydninger.
Forbindelserne med den ovennævnte formel (IV) kan nemt fremstilles ved oxidation af forbindelserne med formlen (I) på i og for sig kendt måde.
Fra beskrivelserne til USA patent nr. 3.748.331 og nr. 3.829.420 er det kendt at fremstille forbindelserne med formlen (I) ved ostsætning af forbindelserne med formlen (II) med forbindelserne med foirin-len (III). Ifølge ovennævnte patentbeskrivelser er det hensigtsmæssigt at anvende arylsulfonsyrer, alkylsulfonsyrer, trifluoreddike-syre eller hydrogenchlorid som katalysator. Ifølge ovennævnte kendte fremgangsmåde er udbyttet af de pågældende forbindelser med formlen (I) imidlertid højst på ca. 20%, selv såfremt der anvendes methansulfonsyre, som beskrives som en foretrukken blandt disse kendte katalysatorer, og desuden dannes en stor mængde biprodukter, når forbindelserne med formlen (II) , hvor X betyder oxygen, anvendes som udgangsmateriale. Når endvidere forbindelserne med formlen (II) , hvor X betyder svovl, anvendes '.som udgangsmateriale, kan de pågældende forbindelser med formlen (I) kun vanskeligt fås ved den kendte fremgangsmåde.
Det har vist sig, at ulemperne ved den kendte fremgangsmåde kan undgås, når ifølge opfindelsen reaktionen gennemføres ved anvendelse af et zinkhalogenid som katalysator, hvorved de tilsigtede 3,4-dihydro-2(IH)-quinazolinonderivater fås i usædvanligt godt udbytte med høj renhed.
Ved gennemførelsen af fremgangsmåden ifølge opfindelsen er den anvendte mængde zinkhalogenid fortrinsvis i området 1-5 molækvivalenter baseret på forbindelsen med formlen (II). Som eksempel på et egnet zinkhalogenid kan nævnes zinkchlorid eller zinkbromid.
Den foreliggende fremgangsmåde kan enten gennemføres i nærværelse eller fraværelse af et indifferent opløsningsmiddel. Imidlertid er det hensigtsmæssigt at gennemføre reaktionen ved opvarmning under tilbagesvaling i et indifferent opløsningsmiddel, som f.eks. toluen, xylen, chlorbenzen, o-chlortoluen, tetrachlorethan med flere, idet det dannede vand fjernes azeotropt ved anvendelse af en vandudskiller.
Nedenstående eksempler illustrerer nærmere fremgangsmåden ifølge opfindelsen.
_ 4 - 141064
Eksempel 1
En blanding af 3,23 g (0,013 mol) N-(2,2,2-trifluorethyl)--N-(p-methoxyphenyl)-urinstof, 1,6 g (0,015 mol) benzaldehyd, 5,3 g (0,039 mol) vandfrit zinkchlorid og 65 ml xylen omrøres et stykke tid, hvorpå blandingen opvarmes under tilbagesvaling i 15 timer under azeotrop fjernelse af det dannede vand. Derpå sættes 20 ml lN-saltsyre til reaktionsblandingen, og blandingen omrøres et stykke tid. Det organiske lag isoleres fra reaktionsblandingen, vaskes med vand, tørres over vandfrit natriumsulfat og inddampes under formindsket tryk. Den fremkomne remanens behandles med isopropylalkohol, der fås 2,71 g (62%) 1-(2,2,2-trifluorethyl)-4-phenyl-6-methoxy--3,4-dihydro-2(IH)-quinazolinon med smp. 168-169UC.
Eksempel 2
Nedenstående forbindelser fås praktisk taget analogt med den i eksempel 1 angivne fremgangsmåde ud fra de tilsvarende udgangsforbindelser med formlen (II) og forbindelserne med formlen (III) i udbytter på 45-65%: 1-(2,2-Difluorethyl)-4-phenyl-6-methoxy-3,4-dihydro-2(IH)-quinazolinon, smp. 128-129°C, 1-(2-chlor-2,2-difluorethyl)-4-phenyl-6-methoxy-3,4-dihydro--2(IH)-quinazolinon, smp. 158-159°C, 1-(2,2,2-trifluorethyl)-4-phenyl-6,7-methylendioxy-3,4-dihydro--2 (IH)-quinazolinon, smp. 199-200°C, 1-(2,2,3,3-tetrafluorpropyl)-4-phenyl-6-methoxy-3,4-dihydro--2 (IH)-quinazolinon, smp. 138-139°C, 1-(2,2,3,3,3-pentafluorpropyl)-4-phenyl-6-methoxy-3,4-dihydro--2(IH)-quinazolinon, smp. 135-136°C, 1-(2,2,3,3,3-pentafluorpropyl)-4-phenyl-6-methy1-3,4-dihydro--2(IH)-quinazolinon, smp. 155-156°C, 1-(2,2,2-trifluorethyl)-4-(2-thienyl)-6-methoxy-3,4-dihydro--2(IH)-quinazolinon, smp. 178-179°C og 1-(2,2,2-trifluorethyl)-4-phenyl-6-methoxy-3,4-dihydro-2(IH)--quinazolinthion, smp. 199-199,5 C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP692076A JPS5291885A (en) | 1976-01-23 | 1976-01-23 | 3,4-dihydro-2(1h)-quinazolinone derivatives |
| JP692076 | 1976-01-23 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK22277A DK22277A (da) | 1977-07-24 |
| DK141064B true DK141064B (da) | 1980-01-07 |
| DK141064C DK141064C (da) | 1980-06-23 |
Family
ID=11651662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK22277AA DK141064B (da) | 1976-01-23 | 1977-01-20 | Fremgangsmåde til fremstilling af 3,4-dihydro-2(1H)-quinazolinonderivater. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4048168A (da) |
| JP (1) | JPS5291885A (da) |
| AT (1) | AT353276B (da) |
| CA (1) | CA1069505A (da) |
| CH (1) | CH625231A5 (da) |
| DE (1) | DE2702530A1 (da) |
| DK (1) | DK141064B (da) |
| FR (1) | FR2338934A1 (da) |
| GB (1) | GB1525892A (da) |
| HU (1) | HU174389B (da) |
| MX (1) | MX3959E (da) |
| NL (1) | NL7614574A (da) |
| SE (1) | SE422324B (da) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5271483A (en) * | 1975-12-11 | 1977-06-14 | Sumitomo Chem Co Ltd | Synthesis of 2(1h)-quinazolinone derivatives |
| US4282226A (en) * | 1978-04-26 | 1981-08-04 | E. R. Squibb & Sons, Inc. | Thioxopyrazolo[1,5-c]quinazoline derivatives, anti-allergic compositions and methods for treating allergic conditions by parenteral administration, aerosol or insufflation |
| EP1394242A3 (en) * | 2002-08-07 | 2004-04-21 | Rohm And Haas Company | Cyclic thioureas and their use as additives for lubricating oils |
| HRP20050633A2 (en) * | 2003-01-23 | 2006-06-30 | Shire Holdings Ag | Formulation and methods for the treatment of thrombocythemia |
| US20060030574A1 (en) * | 2004-08-04 | 2006-02-09 | Shire Holdings Ag | Quinazoline derivatives useful for the treatment of peripheral arterial disease and as phosphodiesterase inhibitors |
| US7700608B2 (en) * | 2004-08-04 | 2010-04-20 | Shire Holdings Ag | Quinazoline derivatives and their use in the treatment of thrombocythemia |
| US7910597B2 (en) * | 2006-11-28 | 2011-03-22 | Shire Llc | Substituted quinazolines |
| US8304420B2 (en) | 2006-11-28 | 2012-11-06 | Shire Llc | Substituted quinazolines for reducing platelet count |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3748331A (en) * | 1971-05-06 | 1973-07-24 | Sandoz Ag | 1,4-disubstituted-methylenedioxy -2-(1h)-quinazolinones and quinazolinthiones |
-
1976
- 1976-01-23 JP JP692076A patent/JPS5291885A/ja active Pending
- 1976-12-27 US US05/754,640 patent/US4048168A/en not_active Expired - Lifetime
- 1976-12-30 NL NL7614574A patent/NL7614574A/xx not_active Application Discontinuation
-
1977
- 1977-01-05 GB GB263/77A patent/GB1525892A/en not_active Expired
- 1977-01-17 FR FR7701170A patent/FR2338934A1/fr active Granted
- 1977-01-17 AT AT22777A patent/AT353276B/de not_active IP Right Cessation
- 1977-01-19 SE SE7700533A patent/SE422324B/xx unknown
- 1977-01-20 DK DK22277AA patent/DK141064B/da not_active IP Right Cessation
- 1977-01-20 CA CA270,156A patent/CA1069505A/en not_active Expired
- 1977-01-21 CH CH78877A patent/CH625231A5/de not_active IP Right Cessation
- 1977-01-21 MX MX775376U patent/MX3959E/es unknown
- 1977-01-21 HU HU77SU937A patent/HU174389B/hu unknown
- 1977-01-21 DE DE19772702530 patent/DE2702530A1/de not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| HU174389B (hu) | 1979-12-28 |
| DK22277A (da) | 1977-07-24 |
| JPS5291885A (en) | 1977-08-02 |
| AU2131477A (en) | 1978-02-23 |
| US4048168A (en) | 1977-09-13 |
| FR2338934B1 (da) | 1980-12-19 |
| CH625231A5 (da) | 1981-09-15 |
| SE7700533L (sv) | 1977-07-24 |
| GB1525892A (en) | 1978-09-20 |
| CA1069505A (en) | 1980-01-08 |
| MX3959E (es) | 1981-10-15 |
| DE2702530A1 (de) | 1977-07-28 |
| DK141064C (da) | 1980-06-23 |
| AT353276B (de) | 1979-11-12 |
| SE422324B (sv) | 1982-03-01 |
| NL7614574A (nl) | 1977-07-26 |
| FR2338934A1 (fr) | 1977-08-19 |
| ATA22777A (de) | 1979-04-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |