CA1192192A - Produits intermediaires pour la synthese de phtalimidines - Google Patents

Produits intermediaires pour la synthese de phtalimidines

Info

Publication number: CA1192192A
Authority: CA; Canada
Prior art keywords: compound; halo; process according; alkyl; formula
Prior art date: 1980-10-31
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000453867A

Other languages

English (en)

Inventor

Joseph Auerbach

Frederick A. Golec, Jr.

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

USV Pharmaceutical Corp

Original Assignee

USV Pharmaceutical Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1980-10-31

Filing date

1984-08-05

Publication date

1985-08-20

1980-10-31 Priority claimed from US06/202,812 external-priority patent/US4331600A/en

1984-08-05 Application filed by USV Pharmaceutical Corp filed Critical USV Pharmaceutical Corp

1985-08-20 Application granted granted Critical

1985-08-20 Publication of CA1192192A publication Critical patent/CA1192192A/fr

Status Expired legal-status Critical Current

Links

239000000543 intermediate Substances 0.000 title abstract description 7
230000015572 biosynthetic process Effects 0.000 title description 3
238000003786 synthesis reaction Methods 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 46
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 20
238000002360 preparation method Methods 0.000 claims abstract description 15
125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
229910052794 bromium Inorganic materials 0.000 claims abstract description 7
229910052801 chlorine Inorganic materials 0.000 claims abstract description 7
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 6
229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract 9
125000001475 halogen functional group Chemical group 0.000 claims abstract 8
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract 6
125000005236 alkanoylamino group Chemical group 0.000 claims abstract 6
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims abstract 3
125000005865 C2-C10alkynyl group Chemical group 0.000 claims abstract 3
125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 38
238000006243 chemical reaction Methods 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 19
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
-1 hydroxylamine compound Chemical class 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
239000005711 Benzoic acid Substances 0.000 claims description 5
229910006080 SO2X Inorganic materials 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
238000006467 substitution reaction Methods 0.000 claims description 5
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 4
229910021529 ammonia Inorganic materials 0.000 claims description 4
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 4
230000000694 effects Effects 0.000 claims description 4
239000000376 reactant Substances 0.000 claims description 4
229910017464 nitrogen compound Inorganic materials 0.000 claims description 3
150000002830 nitrogen compounds Chemical class 0.000 claims description 3
238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
229910006074 SO2NH2 Inorganic materials 0.000 claims 1
238000005935 nucleophilic addition reaction Methods 0.000 claims 1
238000006277 sulfonation reaction Methods 0.000 claims 1
208000024172 Cardiovascular disease Diseases 0.000 abstract description 3
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
239000000243 solution Substances 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
239000000460 chlorine Substances 0.000 description 39
239000000047 product Substances 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
235000002639 sodium chloride Nutrition 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000002253 acid Substances 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 13
229940093499 ethyl acetate Drugs 0.000 description 13
235000019439 ethyl acetate Nutrition 0.000 description 13
239000002244 precipitate Substances 0.000 description 12
239000002904 solvent Substances 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 description 11
239000000203 mixture Substances 0.000 description 11
229960000583 acetic acid Drugs 0.000 description 10
239000012043 crude product Substances 0.000 description 10
239000012362 glacial acetic acid Substances 0.000 description 10
238000010992 reflux Methods 0.000 description 8
239000007858 starting material Substances 0.000 description 8
125000000217 alkyl group Chemical group 0.000 description 7
LLHRMWHYJGLIEV-UHFFFAOYSA-N desoxy Chemical group COC1=CC(CCN)=CC(OC)=C1C LLHRMWHYJGLIEV-UHFFFAOYSA-N 0.000 description 7
239000003814 drug Substances 0.000 description 7
125000005843 halogen group Chemical group 0.000 description 7
229940124597 therapeutic agent Drugs 0.000 description 7
238000003828 vacuum filtration Methods 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
230000003647 oxidation Effects 0.000 description 6
238000007254 oxidation reaction Methods 0.000 description 6
230000001225 therapeutic effect Effects 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
235000011167 hydrochloric acid Nutrition 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
239000007800 oxidant agent Substances 0.000 description 5
230000035484 reaction time Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
239000011701 zinc Substances 0.000 description 5
229910052725 zinc Inorganic materials 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000000284 extract Substances 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
229960000443 hydrochloric acid Drugs 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
238000006213 oxygenation reaction Methods 0.000 description 4
238000000746 purification Methods 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
239000003513 alkali Substances 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000001914 filtration Methods 0.000 description 3
238000002955 isolation Methods 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical class C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
208000027032 Renal vascular disease Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
125000000304 alkynyl group Chemical group 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000000538 analytical sample Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
150000001768 cations Chemical class 0.000 description 2
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
229910000366 copper(II) sulfate Inorganic materials 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000002934 diuretic Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229940099594 manganese dioxide Drugs 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 2
238000004452 microanalysis Methods 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
230000001590 oxidative effect Effects 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
UIVIXKOOYPLSIB-UHFFFAOYSA-N phthalazin-1-one Chemical compound C1=CC=C[C]2C(=O)N=NC=C21 UIVIXKOOYPLSIB-UHFFFAOYSA-N 0.000 description 2
125000005506 phthalide group Chemical group 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000007787 solid Substances 0.000 description 2
230000003595 spectral effect Effects 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
UKRADWWBRBBJLZ-UHFFFAOYSA-N 2-(4-chloro-3-sulfamoylbenzoyl)benzoic acid Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(=O)C=2C(=CC=CC=2)C(O)=O)=C1 UKRADWWBRBBJLZ-UHFFFAOYSA-N 0.000 description 1
YWECCEXWKFHHQJ-UHFFFAOYSA-N 2-(4-chlorobenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(Cl)C=C1 YWECCEXWKFHHQJ-UHFFFAOYSA-N 0.000 description 1
YRLWBFRYPAFHNL-UHFFFAOYSA-N 2-chloro-5-(4-oxo-3h-phthalazin-1-yl)benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C=2C3=CC=CC=C3C(=O)NN=2)=C1 YRLWBFRYPAFHNL-UHFFFAOYSA-N 0.000 description 1
JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
FPFSGDXIBUDDKZ-UHFFFAOYSA-N 3-decyl-2-hydroxycyclopent-2-en-1-one Chemical compound CCCCCCCCCCC1=C(O)C(=O)CC1 FPFSGDXIBUDDKZ-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
ZWWXEGPFZYMTNJ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2H-phthalazin-1-one Chemical compound ClC1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O.ClC1=CC=C(C=C1)C1=NNC(C2=CC=CC=C12)=O ZWWXEGPFZYMTNJ-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
FBXGQDUVJBKEAJ-UHFFFAOYSA-N 4h-oxazin-3-one Chemical group O=C1CC=CON1 FBXGQDUVJBKEAJ-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical class F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
240000008881 Oenanthe javanica 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
239000005708 Sodium hypochlorite Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
IRAKVRJJLPZVGE-UHFFFAOYSA-L acetic acid;dihydroxy(dioxo)chromium Chemical compound CC(O)=O.O[Cr](O)(=O)=O IRAKVRJJLPZVGE-UHFFFAOYSA-L 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000005915 ammonolysis reaction Methods 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
239000000043 antiallergic agent Substances 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000012431 aqueous reaction media Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
125000000068 chlorophenyl group Chemical group 0.000 description 1
229960001523 chlortalidone Drugs 0.000 description 1
ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical class [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
239000004927 clay Substances 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
229940045803 cuprous chloride Drugs 0.000 description 1
238000006392 deoxygenation reaction Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000428 dust Substances 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
IMBKASBLAKCLEM-UHFFFAOYSA-L ferrous ammonium sulfate (anhydrous) Chemical compound [NH4+].[NH4+].[Fe+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O IMBKASBLAKCLEM-UHFFFAOYSA-L 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical class Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
239000000155 melt Substances 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
GEMHFKXPOCTAIP-UHFFFAOYSA-N n,n-dimethyl-n'-phenylcarbamimidoyl chloride Chemical compound CN(C)C(Cl)=NC1=CC=CC=C1 GEMHFKXPOCTAIP-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
YMVDIDRLTRKWOW-UHFFFAOYSA-N oxazin-6-one Chemical compound O=C1C=CC=NO1 YMVDIDRLTRKWOW-UHFFFAOYSA-N 0.000 description 1
125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical class OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical class C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
125000005543 phthalimide group Chemical group 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000000079 presaturation Methods 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000011946 reduction process Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
229910052712 strontium Inorganic materials 0.000 description 1
239000000758 substrate Substances 0.000 description 1
238000000967 suction filtration Methods 0.000 description 1
125000000565 sulfonamide group Chemical group 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000453867A 1980-10-31 1984-08-05 Produits intermediaires pour la synthese de phtalimidines Expired CA1192192A (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US06/202,812 US4331600A (en)	1980-10-31	1980-10-31	Intermediates for the synthesis of phthalimidines
US202,812		1980-10-31
CA000389082A CA1172634A (fr)	1980-10-31	1981-10-30	Produits intermediaires pour la synthese des phtalimidines

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000389082A Division CA1172634A (fr)	1980-10-31	1981-10-30	Produits intermediaires pour la synthese des phtalimidines

Publications (1)

Publication Number	Publication Date
CA1192192A true CA1192192A (fr)	1985-08-20

Family

ID=25669478

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000453867A Expired CA1192192A (fr)	1980-10-31	1984-08-05	Produits intermediaires pour la synthese de phtalimidines

Country Status (1)

Country	Link
CA (1)	CA1192192A (fr)

1984
- 1984-08-05 CA CA000453867A patent/CA1192192A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2002-08-20	MKEX	Expiry
2023-05-26	MKEX	Expiry	Effective date: 20020820

Publication	Publication Date	Title
US4327222A (en)	1982-04-27	3,4-Diarylisoxazol-5-acetic acids and process for making same
CA1172634A (fr)	1984-08-14	Produits intermediaires pour la synthese des phtalimidines
JPS58164570A (ja)	1983-09-29	アセメタシンの製造法
FR2493147A1 (fr)	1982-05-07	Compositions pharmaceutiques contenant des pyranones substituees en position 6
US4400520A (en)	1983-08-23	Novel process for preparing isoindoline derivatives
EP0138490B1 (fr)	1988-04-27	Alkyl-4-méthylènedioxy-1[H]-quinazolinones-2
US4034045A (en)	1977-07-05	2,4-Disubstituted-4b,5,6,7,8,8a,9,10-octahydro-9-oxo-phenanthrenes
JPS5927343B2 (ja)	1984-07-05	３−アミノイソオキサゾ−ル類の合成法
PL114677B1 (en)	1981-02-28	Process for preparing novel derivatives of 6,7-dimethoxy-1,2,3,4-tetrahydro-1-isoquinolinoacetamide
US3598861A (en)	1971-08-10	2-(5'-phenyl-m-terphenyl - 4 - yloxy) lower aliphatic monocarbocyclic acids and esters thereof
JPS62205043A (ja)	1987-09-09	９，１０−ジヒドロ−フエナントレン誘導体およびその製法
JPH0586042A (ja)	1993-04-06	２−メルカプト−フエノチアジンの製造方法
US4176196A (en)	1979-11-27	Hypoglycemic arylcyclohexane acetic acids
JPS6051473B2 (ja)	1985-11-14	４−置換フエニルフタラジン誘導体
JP2744653B2 (ja)	1998-04-28	ジフエニルメチルアミン誘導体
KR820001835B1 (ko)	1982-10-13	4-아미노-2-피페리디노퀴나졸린 유도체의 제조방법
CH650255A5 (fr)	1985-07-15	Derives d'imidazole, leur procede de preparation et composition pharmaceutique les contenant.
JPS58148870A (ja)	1983-09-05	２−〔４−（２−チアゾリルオキシ）フエニル〕プロピオン酸の工業的製造法
JPH0267278A (ja)	1990-03-07	ベンゾジオキソール誘導体
EP0051217A1 (fr)	1982-05-12	Procédé d'oxydation
JPS61268679A (ja)	1986-11-28	２−チオクロメニリデンアセト酢酸エステルの製法
JPS6110560A (ja)	1986-01-18	２−タ−シヤリ−ブチル−４，　５−ジクロル−３　（２ｈ）−ピリダジノンの製法
JPH01261355A (ja)	1989-10-18	安息香酸誘導体の製造方法
JPS59176268A (ja)	1984-10-05	スピロイソキサゾリン化合物
JPS58164573A (ja)	1983-09-29	１−（４−クロロベンゾイル）−５−メトキシ−２−メチル−３−インド−ルアセトキシ酢酸類の製法