DE2438966A1 - Basisch substituierte 3,,4-dihydro2h-isochinolin-1-one und verfahren zu ihrer herstellung - Google Patents
Basisch substituierte 3,,4-dihydro2h-isochinolin-1-one und verfahren zu ihrer herstellungInfo
- Publication number
- DE2438966A1 DE2438966A1 DE19742438966 DE2438966A DE2438966A1 DE 2438966 A1 DE2438966 A1 DE 2438966A1 DE 19742438966 DE19742438966 DE 19742438966 DE 2438966 A DE2438966 A DE 2438966A DE 2438966 A1 DE2438966 A1 DE 2438966A1
- Authority
- DE
- Germany
- Prior art keywords
- formula
- dihydro
- compound
- isoquinolin
- meaning given
- Prior art date
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 67
- YWPMKTWUFVOFPL-UHFFFAOYSA-N 3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(=O)NCCC2=C1 YWPMKTWUFVOFPL-UHFFFAOYSA-N 0.000 title description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 67
- -1 2-Diisopropylaminoethyl Chemical group 0.000 claims description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 230000029936 alkylation Effects 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 6
- 230000003288 anthiarrhythmic effect Effects 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 150000002923 oximes Chemical class 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 150000003862 amino acid derivatives Chemical class 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 150000003949 imides Chemical class 0.000 claims description 3
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical class NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 150000002596 lactones Chemical group 0.000 claims description 2
- 230000008707 rearrangement Effects 0.000 claims description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 239000003416 antiarrhythmic agent Substances 0.000 claims 2
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
- NKSZCPBUWGZONP-UHFFFAOYSA-N 3,4-dihydroisoquinoline Chemical class C1=CC=C2C=NCCC2=C1 NKSZCPBUWGZONP-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 16
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 14
- 239000012442 inert solvent Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 239000002585 base Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 6
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
- 150000003335 secondary amines Chemical class 0.000 description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- 150000002540 isothiocyanates Chemical class 0.000 description 5
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 239000008164 mustard oil Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- VPYIIVAOZQDMBH-UHFFFAOYSA-N 5-isothiocyanato-n,n-dimethyl-4,4-diphenylpentan-1-amine Chemical compound C=1C=CC=CC=1C(CN=C=S)(CCCN(C)C)C1=CC=CC=C1 VPYIIVAOZQDMBH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 235000013877 carbamide Nutrition 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 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
- 239000005457 ice water Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 150000003585 thioureas Chemical class 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- NTNKZGHUNBWBBV-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-isoquinolin-1-one Chemical compound C1C=CC=C2C(=O)NCCC21 NTNKZGHUNBWBBV-UHFFFAOYSA-N 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229940112021 centrally acting muscle relaxants carbamic acid ester Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical class C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 150000002927 oxygen compounds Chemical class 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- CPEONABTMRSIKA-UHFFFAOYSA-N 1,4$l^{2}-oxazinane Chemical compound C1COCC[N]1 CPEONABTMRSIKA-UHFFFAOYSA-N 0.000 description 1
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- QVVFXYSMWXIJQM-UHFFFAOYSA-N 1-(5-isocyanato-4,4-diphenylpentyl)piperidine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(CN=C=O)CCCN1CCCCC1 QVVFXYSMWXIJQM-UHFFFAOYSA-N 0.000 description 1
- RGVPOXRFEPSFGH-UHFFFAOYSA-N 1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol Chemical compound COC1=C(OC)C(OC)=CC(CC2C3=CC(O)=C(O)C=C3CCN2)=C1 RGVPOXRFEPSFGH-UHFFFAOYSA-N 0.000 description 1
- WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
- VFGGBORNHGKXDZ-UHFFFAOYSA-N 2,2-diphenyl-4-piperidin-1-ylbutan-1-amine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(CN)CCN1CCCCC1 VFGGBORNHGKXDZ-UHFFFAOYSA-N 0.000 description 1
- GDSAWKYILHIKBA-UHFFFAOYSA-N 2,3,4a,5-tetrahydro-1h-isoquinolin-4-one Chemical compound C1=CCC2C(=O)CNCC2=C1 GDSAWKYILHIKBA-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- IRXWBCKPECPALY-UHFFFAOYSA-N 3,4-dihydro-2h-isoquinoline-1-thione Chemical class C1=CC=C2C(=S)NCCC2=C1 IRXWBCKPECPALY-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
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- NXLQDNROFXLLDC-UHFFFAOYSA-N ethyl n-[4-(diethylamino)-2,2-diphenylbutyl]carbamate Chemical compound C=1C=CC=CC=1C(CCN(CC)CC)(CNC(=O)OCC)C1=CC=CC=C1 NXLQDNROFXLLDC-UHFFFAOYSA-N 0.000 description 1
- ZMGWTLDUTWBIKM-UHFFFAOYSA-N ethyl n-[4-[di(propan-2-yl)amino]-2,2-diphenylbutyl]carbamate Chemical compound C=1C=CC=CC=1C(CCN(C(C)C)C(C)C)(CNC(=O)OCC)C1=CC=CC=C1 ZMGWTLDUTWBIKM-UHFFFAOYSA-N 0.000 description 1
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- 239000011261 inert gas Substances 0.000 description 1
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- 239000011147 inorganic material Substances 0.000 description 1
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- 238000005342 ion exchange Methods 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
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- 239000008101 lactose Substances 0.000 description 1
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- 230000007935 neutral effect Effects 0.000 description 1
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- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
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- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 229940100684 pentylamine Drugs 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000004053 quinones Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000003464 sulfur compounds Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or 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 to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or 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 to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742438966 DE2438966A1 (de) | 1974-08-14 | 1974-08-14 | Basisch substituierte 3,,4-dihydro2h-isochinolin-1-one und verfahren zu ihrer herstellung |
| NL7509486A NL7509486A (nl) | 1974-08-14 | 1975-08-08 | Werkwijze voor het bereiden van basisch gesub- stitueerde 3,4-dihydro-2h-isochinoline-1-onen. |
| LU73197A LU73197A1 (enExample) | 1974-08-14 | 1975-08-12 | |
| IE180275A IE41512B1 (en) | 1974-08-14 | 1975-08-13 | 3,4-dihydro-2h-isoquinoline-1-ones and process for preparing them |
| AT629775A AT349019B (de) | 1974-08-14 | 1975-08-13 | Verfahren zur herstellung von neuen, basisch substituierten 3,4-dihydro-2h-isochinolin-1- onen und ihren salzen |
| CA233,696A CA1055027A (en) | 1974-08-14 | 1975-08-13 | Basically substituted 3,4-dihydro-2h-isoquinolin-1-thiones and process for preparing them |
| DK367175A DK367175A (da) | 1974-08-14 | 1975-08-13 | Basisk substituerede 3,4-dihydro-2h-isoquinolin-1-oner samt fremgangsmade til fremstilling deraf |
| FR7525344A FR2281763A1 (fr) | 1974-08-14 | 1975-08-14 | 3,4-dihydro-2h-isoquinoleine-1-ones a substituant basique, leur procede de preparation et leurs applications |
| BE159241A BE832470A (fr) | 1974-08-14 | 1975-08-14 | 3,4-dihydro-2h-isoquinoleine-1-ones a substituant basique, leur procede de preparation et leurs applications |
| JP9904375A JPS5143767A (en) | 1974-08-14 | 1975-08-14 | Enkiseichikan 3 44 jihidoro 2hh isokinorin 11 onno seizohoho |
| GB3388975A GB1516535A (en) | 1974-08-14 | 1975-08-14 | 3,4-dihydro-2h-isoquinoline-1-ones and process for preparing them |
| US05/754,168 US4118494A (en) | 1974-08-14 | 1976-12-27 | Substituted 3,4-dihydro-2H-isoquinolin-1-thiones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742438966 DE2438966A1 (de) | 1974-08-14 | 1974-08-14 | Basisch substituierte 3,,4-dihydro2h-isochinolin-1-one und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2438966A1 true DE2438966A1 (de) | 1976-03-04 |
Family
ID=5923161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742438966 Pending DE2438966A1 (de) | 1974-08-14 | 1974-08-14 | Basisch substituierte 3,,4-dihydro2h-isochinolin-1-one und verfahren zu ihrer herstellung |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5143767A (enExample) |
| AT (1) | AT349019B (enExample) |
| BE (1) | BE832470A (enExample) |
| CA (1) | CA1055027A (enExample) |
| DE (1) | DE2438966A1 (enExample) |
| DK (1) | DK367175A (enExample) |
| FR (1) | FR2281763A1 (enExample) |
| GB (1) | GB1516535A (enExample) |
| IE (1) | IE41512B1 (enExample) |
| LU (1) | LU73197A1 (enExample) |
| NL (1) | NL7509486A (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58203968A (ja) * | 1982-05-21 | 1983-11-28 | Otsuka Pharmaceut Co Ltd | イソカルボスチリル誘導体 |
| ES2382009T3 (es) * | 2006-12-01 | 2012-06-04 | Bristol-Myers Squibb Company | Derivados de N-((3-bencil)-2,2-(bis-fenil-)-propan-1-amina como inhibidores de CETP para el tratamiento de aterosclerosis y enfermedades cardiovasculares |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2143744A1 (de) * | 1971-09-01 | 1973-03-08 | Hoechst Ag | 3,4-dihydro-2h-isochinolin-1-one und verfahren zu ihrer herstellung |
-
1974
- 1974-08-14 DE DE19742438966 patent/DE2438966A1/de active Pending
-
1975
- 1975-08-08 NL NL7509486A patent/NL7509486A/xx unknown
- 1975-08-12 LU LU73197A patent/LU73197A1/xx unknown
- 1975-08-13 CA CA233,696A patent/CA1055027A/en not_active Expired
- 1975-08-13 IE IE180275A patent/IE41512B1/en unknown
- 1975-08-13 AT AT629775A patent/AT349019B/de not_active IP Right Cessation
- 1975-08-13 DK DK367175A patent/DK367175A/da not_active Application Discontinuation
- 1975-08-14 GB GB3388975A patent/GB1516535A/en not_active Expired
- 1975-08-14 JP JP9904375A patent/JPS5143767A/ja active Pending
- 1975-08-14 FR FR7525344A patent/FR2281763A1/fr active Granted
- 1975-08-14 BE BE159241A patent/BE832470A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5143767A (en) | 1976-04-14 |
| AT349019B (de) | 1979-03-12 |
| NL7509486A (nl) | 1976-02-17 |
| ATA629775A (de) | 1978-08-15 |
| FR2281763B1 (enExample) | 1978-09-01 |
| FR2281763A1 (fr) | 1976-03-12 |
| DK367175A (da) | 1976-02-15 |
| LU73197A1 (enExample) | 1977-04-13 |
| IE41512B1 (en) | 1980-01-16 |
| GB1516535A (en) | 1978-07-05 |
| BE832470A (fr) | 1976-02-16 |
| IE41512L (en) | 1976-02-14 |
| CA1055027A (en) | 1979-05-22 |
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