DD140145A5 - Verfahren zur herstellung von 4-amino-2-piperidino-chinazolin-derivaten - Google Patents

Verfahren zur herstellung von 4-amino-2-piperidino-chinazolin-derivaten Download PDF

Info

Publication number: DD140145A5
Authority: DD; German Democratic Republic
Prior art keywords: och; piperidine; chloroform; residue; formula
Prior art date: 1977-11-16

Application number

DD20913378A

Other languages

German (de)

English (en)

Inventor

Simon F Campbell

John C Danilewicz

Colin W Greengrass

Original Assignee

Pfizer

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.)

1977-11-16

Filing date

1978-11-16

Publication date

1980-02-13

1978-11-16 Application filed by Pfizer filed Critical Pfizer

1980-02-13 Publication of DD140145A5 publication Critical patent/DD140145A5/de

Links

238000004519 manufacturing process Methods 0.000 title 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 35
150000001875 compounds Chemical class 0.000 claims description 32
125000000217 alkyl group Chemical group 0.000 claims description 19
238000002360 preparation method Methods 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
-1 C 1 -C 4 -alkyl Chemical group 0.000 claims description 12
238000000034 method Methods 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 7
150000002431 hydrogen Chemical group 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
125000004414 alkyl thio group Chemical group 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 69
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 30
239000002904 solvent Substances 0.000 description 26
238000004458 analytical method Methods 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
239000000203 mixture Substances 0.000 description 19
239000011734 sodium Substances 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
229910000104 sodium hydride Inorganic materials 0.000 description 15
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 14
239000000047 product Substances 0.000 description 14
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
229910000041 hydrogen chloride Inorganic materials 0.000 description 13
239000000725 suspension Substances 0.000 description 13
239000008346 aqueous phase Substances 0.000 description 11
239000002026 chloroform extract Substances 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
229960004592 isopropanol Drugs 0.000 description 10
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
239000012312 sodium hydride Substances 0.000 description 9
150000003053 piperidines Chemical class 0.000 description 8
239000007787 solid Substances 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000003814 drug Substances 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
239000002480 mineral oil Substances 0.000 description 7
235000010446 mineral oil Nutrition 0.000 description 7
239000012299 nitrogen atmosphere Substances 0.000 description 7
239000000523 sample Substances 0.000 description 7
KZPIFQYDCVCSDS-UHFFFAOYSA-N 1-(4-hydroxypiperidin-1-yl)ethanone Chemical compound CC(=O)N1CCC(O)CC1 KZPIFQYDCVCSDS-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
239000006185 dispersion Substances 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000000284 extract Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
NJCJXKIBQLPVPM-UHFFFAOYSA-N 1-[4-(2-hydroxyethoxy)piperidin-1-yl]ethanone Chemical compound CC(=O)N1CCC(OCCO)CC1 NJCJXKIBQLPVPM-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
HWIIAAVGRHKSOJ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 HWIIAAVGRHKSOJ-UHFFFAOYSA-N 0.000 description 3
MNRJBWWZVOCYSN-UHFFFAOYSA-N 4-(2-methoxypropoxy)piperidine Chemical compound COC(C)COC1CCNCC1 MNRJBWWZVOCYSN-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
238000004821 distillation Methods 0.000 description 3
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
LLMZNCCAWHTARU-UHFFFAOYSA-N 1-[4-(2,2-diethoxyethoxy)piperidin-1-yl]ethanone Chemical compound CCOC(OCC)COC1CCN(C(C)=O)CC1 LLMZNCCAWHTARU-UHFFFAOYSA-N 0.000 description 2
KPRSMNXEKIFCMX-UHFFFAOYSA-N 1-piperidin-4-yloxypropan-2-ol Chemical compound CC(O)COC1CCNCC1 KPRSMNXEKIFCMX-UHFFFAOYSA-N 0.000 description 2
LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 2
VAIHBHWKPBXNLR-UHFFFAOYSA-N 2-piperidin-4-yloxyethanol Chemical compound OCCOC1CCNCC1 VAIHBHWKPBXNLR-UHFFFAOYSA-N 0.000 description 2
WNZCEVHUMWODJS-UHFFFAOYSA-N 4-[2-(4-fluorophenoxy)ethoxy]piperidine Chemical compound C1=CC(F)=CC=C1OCCOC1CCNCC1 WNZCEVHUMWODJS-UHFFFAOYSA-N 0.000 description 2
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
241000282412 Homo Species 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
230000003276 anti-hypertensive effect Effects 0.000 description 2
239000002585 base Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000011097 chromatography purification Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
KAQVFEITQMBSEF-UHFFFAOYSA-N cyclopentyl methanesulfonate Chemical compound CS(=O)(=O)OC1CCCC1 KAQVFEITQMBSEF-UHFFFAOYSA-N 0.000 description 2
239000012458 free base Substances 0.000 description 2
PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
235000006408 oxalic acid Nutrition 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
150000003246 quinazolines Chemical class 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
LFRHMTZYADABJZ-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)butan-2-amine;hydron;chloride Chemical compound Cl.CCC(N)CC1=CC=C2OCOC2=C1 LFRHMTZYADABJZ-UHFFFAOYSA-N 0.000 description 1
ZNOFYDOYQNIMRS-UHFFFAOYSA-N 1-[4-(2-hydroxypropoxy)piperidin-1-yl]ethanone Chemical compound CC(O)COC1CCN(C(C)=O)CC1 ZNOFYDOYQNIMRS-UHFFFAOYSA-N 0.000 description 1
HKHAOLJNVGPHEM-UHFFFAOYSA-N 1-[4-(2-methoxypropoxy)piperidin-1-yl]ethanone Chemical compound COC(C)COC1CCN(C(C)=O)CC1 HKHAOLJNVGPHEM-UHFFFAOYSA-N 0.000 description 1
FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
NHZJKZSPOHSVNK-UHFFFAOYSA-N 2-piperidin-1-yloxyethanol Chemical compound OCCON1CCCCC1 NHZJKZSPOHSVNK-UHFFFAOYSA-N 0.000 description 1
MDGLKMXWHKGENE-UHFFFAOYSA-N 2-piperidin-1-ylquinazolin-4-amine Chemical class N=1C2=CC=CC=C2C(N)=NC=1N1CCCCC1 MDGLKMXWHKGENE-UHFFFAOYSA-N 0.000 description 1
NGMMGKYJUWYIIG-UHFFFAOYSA-N 3-hydroxybenzamide Chemical compound NC(=O)C1=CC=CC(O)=C1 NGMMGKYJUWYIIG-UHFFFAOYSA-N 0.000 description 1
IJDWIEIJKIGROU-UHFFFAOYSA-N 4-(2-cyclopentyloxyethoxy)piperidine Chemical compound C1CCCC1OCCOC1CCNCC1 IJDWIEIJKIGROU-UHFFFAOYSA-N 0.000 description 1
JSCHXBPVXYQFGH-UHFFFAOYSA-N 4-(2-cyclopentyloxyethoxy)piperidine;hydrochloride Chemical compound Cl.C1CCCC1OCCOC1CCNCC1 JSCHXBPVXYQFGH-UHFFFAOYSA-N 0.000 description 1
YUAFBJXCTHYOSJ-UHFFFAOYSA-N 4-(2-ethoxyethoxy)piperidine Chemical compound CCOCCOC1CCNCC1 YUAFBJXCTHYOSJ-UHFFFAOYSA-N 0.000 description 1
NVESPAGIUWPFCX-UHFFFAOYSA-N 4-(2-ethoxypropoxy)piperidine Chemical compound CCOC(C)COC1CCNCC1 NVESPAGIUWPFCX-UHFFFAOYSA-N 0.000 description 1
KTXVOCUROHMWQP-UHFFFAOYSA-N 4-(2-methoxyethoxy)piperidine Chemical compound COCCOC1CCNCC1 KTXVOCUROHMWQP-UHFFFAOYSA-N 0.000 description 1
LCBWBBJCOKLDQY-UHFFFAOYSA-N 4-(2-phenoxypropoxy)piperidine Chemical compound C=1C=CC=CC=1OC(C)COC1CCNCC1 LCBWBBJCOKLDQY-UHFFFAOYSA-N 0.000 description 1
QFXUVUTWGVBESE-UHFFFAOYSA-N 4-(2-propan-2-yloxyethoxy)piperidine Chemical compound CC(C)OCCOC1CCNCC1 QFXUVUTWGVBESE-UHFFFAOYSA-N 0.000 description 1
AZEIRPAUJXANCS-UHFFFAOYSA-N 4-ethoxybenzamide Chemical compound CCOC1=CC=C(C(N)=O)C=C1 AZEIRPAUJXANCS-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
229910014033 C-OH Inorganic materials 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
229910014570 C—OH Inorganic materials 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
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239000013543 active substance Substances 0.000 description 1
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230000036772 blood pressure Effects 0.000 description 1
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210000000748 cardiovascular system Anatomy 0.000 description 1
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229940050410 gluconate Drugs 0.000 description 1
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VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical compound [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
RLXDCJUIXHSXQD-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O.OC(=O)C(O)=O RLXDCJUIXHSXQD-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
DLRJIFUOBPOJNS-UHFFFAOYSA-N phenetole Chemical compound CCOC1=CC=CC=C1 DLRJIFUOBPOJNS-UHFFFAOYSA-N 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
238000000053 physical method Methods 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
210000002966 serum Anatomy 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
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000011699 spontaneously hypertensive rat Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

DD20913378A 1977-11-16 1978-11-16 Verfahren zur herstellung von 4-amino-2-piperidino-chinazolin-derivaten DD140145A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB4758377		1977-11-16

Publications (1)

Publication Number	Publication Date
DD140145A5 true DD140145A5 (de)	1980-02-13

Family

ID=10445508

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD20913378A DD140145A5 (de)	1977-11-16	1978-11-16	Verfahren zur herstellung von 4-amino-2-piperidino-chinazolin-derivaten

Country Status (16)

Country	Link
AR (1)	AR219773A1 (pl)
DD (1)	DD140145A5 (pl)
DK (1)	DK440378A (pl)
ES (1)	ES475122A1 (pl)
FI (1)	FI63935C (pl)
GR (1)	GR72239B (pl)
IE (1)	IE47510B1 (pl)
IL (1)	IL55934A (pl)
IT (1)	IT1101414B (pl)
NO (1)	NO783829L (pl)
NZ (1)	NZ188915A (pl)
PH (1)	PH13927A (pl)
PL (1)	PL112638B1 (pl)
PT (1)	PT68784A (pl)
YU (1)	YU263878A (pl)
ZA (1)	ZA786423B (pl)

1978
- 1978-10-04 DK DK440378A patent/DK440378A/da not_active Application Discontinuation
- 1978-10-30 PH PH21753A patent/PH13927A/en unknown
- 1978-11-14 PT PT6878478A patent/PT68784A/pt unknown
- 1978-11-14 NZ NZ18891578A patent/NZ188915A/xx unknown
- 1978-11-14 NO NO783829A patent/NO783829L/no unknown
- 1978-11-14 IL IL55934A patent/IL55934A/xx unknown
- 1978-11-14 AR AR27442578A patent/AR219773A1/es active
- 1978-11-14 FI FI783477A patent/FI63935C/fi not_active IP Right Cessation
- 1978-11-14 IT IT29773/78A patent/IT1101414B/it active
- 1978-11-14 YU YU263878A patent/YU263878A/xx unknown
- 1978-11-15 ES ES475122A patent/ES475122A1/es not_active Expired
- 1978-11-15 ZA ZA00786423A patent/ZA786423B/xx unknown
- 1978-11-15 IE IE225478A patent/IE47510B1/en unknown
- 1978-11-15 GR GR57654A patent/GR72239B/el unknown
- 1978-11-16 DD DD20913378A patent/DD140145A5/de unknown
- 1978-11-16 PL PL21098278A patent/PL112638B1/pl unknown

Also Published As

Publication number	Publication date
PH13927A (en)	1980-11-04
NO783829L (no)	1979-05-18
ES475122A1 (es)	1979-05-16
IT7829773A0 (it)	1978-11-14
NZ188915A (en)	1980-08-26
IE47510B1 (en)	1984-04-04
FI63935B (fi)	1983-05-31
PL112638B1 (en)	1980-10-31
IL55934A0 (en)	1979-01-31
DK440378A (da)	1979-05-17
FI63935C (fi)	1983-09-12
IL55934A (en)	1982-08-31
ZA786423B (en)	1979-10-31
GR72239B (pl)	1983-10-03
PL210982A1 (pl)	1979-06-18
AR219773A1 (es)	1980-09-15
YU263878A (en)	1982-08-31
IE782254L (en)	1979-05-16
FI783477A7 (fi)	1979-05-17
IT1101414B (it)	1985-09-28
PT68784A (en)	1978-12-01

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