CS231970B2 - Manufacturing process of the 4-amino-2-peperidinochinazoline derivatives - Google Patents
Manufacturing process of the 4-amino-2-peperidinochinazoline derivatives Download PDFInfo
- Publication number
- CS231970B2 CS231970B2 CS80607A CS60780A CS231970B2 CS 231970 B2 CS231970 B2 CS 231970B2 CS 80607 A CS80607 A CS 80607A CS 60780 A CS60780 A CS 60780A CS 231970 B2 CS231970 B2 CS 231970B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- piperidine
- phenyl
- amino
- vacuo
- evaporated
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- -1 (phenyl) - Chemical class 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- IYSAKEZXXWXRBM-UHFFFAOYSA-N NC1=CC(=NC2=CC=CC=C12)N1CCCCC1 Chemical class NC1=CC(=NC2=CC=CC=C12)N1CCCCC1 IYSAKEZXXWXRBM-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 239000000047 product Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000002026 chloroform extract Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- DNKXLUPNIXJUED-UHFFFAOYSA-N 4-(2-ethoxy-1-phenylethoxy)piperidine Chemical compound C=1C=CC=CC=1C(COCC)OC1CCNCC1 DNKXLUPNIXJUED-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 150000003891 oxalate salts Chemical class 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 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 3
- 206010020772 Hypertension Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
- KZPIFQYDCVCSDS-UHFFFAOYSA-N 1-(4-hydroxypiperidin-1-yl)ethanone Chemical compound CC(=O)N1CCC(O)CC1 KZPIFQYDCVCSDS-UHFFFAOYSA-N 0.000 description 2
- VUOXOBUGCOTNBV-UHFFFAOYSA-N 1-[4-(2-hydroxy-1-phenylethoxy)piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1OC(CO)C1=CC=CC=C1 VUOXOBUGCOTNBV-UHFFFAOYSA-N 0.000 description 2
- XBFLETFUQPUNHF-UHFFFAOYSA-N 1-[4-[2-(2-hydroxyphenyl)ethoxy]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1OCCC1=CC=CC=C1O XBFLETFUQPUNHF-UHFFFAOYSA-N 0.000 description 2
- VQEYXSPZCWGXAC-UHFFFAOYSA-N 2-[4-(2-ethoxy-1-phenylethoxy)piperidin-1-yl]-6,7-dimethoxyquinazolin-4-amine;hydrochloride Chemical compound Cl.C1CN(C=2N=C3C=C(OC)C(OC)=CC3=C(N)N=2)CCC1OC(COCC)C1=CC=CC=C1 VQEYXSPZCWGXAC-UHFFFAOYSA-N 0.000 description 2
- QZYFOOHHZWNYEW-UHFFFAOYSA-N 2-phenyl-1-piperidin-4-yloxypropan-2-ol Chemical compound C=1C=CC=CC=1C(O)(C)COC1CCNCC1 QZYFOOHHZWNYEW-UHFFFAOYSA-N 0.000 description 2
- JHHLUDVQZWAIOV-UHFFFAOYSA-N 4-(2-phenoxy-1-phenylethoxy)piperidine Chemical compound C1CNCCC1OC(C=1C=CC=CC=1)COC1=CC=CC=C1 JHHLUDVQZWAIOV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BAGJZDKQXIKUEX-UHFFFAOYSA-N 6,7-dimethoxy-2-[4-(2-phenoxy-1-phenylethoxy)piperidin-1-yl]quinazolin-4-amine hydrate hydrochloride Chemical compound O.Cl.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCC1OC(C=1C=CC=CC=1)COC1=CC=CC=C1 BAGJZDKQXIKUEX-UHFFFAOYSA-N 0.000 description 2
- GDHADTLPFJMCOI-UHFFFAOYSA-N 6-(cyclopropylmethoxy)-2-[4-(2-ethoxy-1-phenylethoxy)piperidin-1-yl]-7-methoxyquinazolin-4-amine Chemical compound NC1=NC(=NC2=CC(=C(C=C12)OCC1CC1)OC)N1CCC(CC1)OC(COCC)C1=CC=CC=C1 GDHADTLPFJMCOI-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
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- 239000000543 intermediate Substances 0.000 description 2
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- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 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 2
- DCFIFQMXQJMGPV-UHFFFAOYSA-N 1-[4-[2-(2-ethoxyphenyl)ethoxy]piperidin-1-yl]ethanone Chemical compound CCOC1=CC=CC=C1CCOC1CCN(C(C)=O)CC1 DCFIFQMXQJMGPV-UHFFFAOYSA-N 0.000 description 1
- AHOJTPZHHMJMCW-UHFFFAOYSA-N 1-ethylpiperidin-4-ol Chemical compound CCN1CCC(O)CC1 AHOJTPZHHMJMCW-UHFFFAOYSA-N 0.000 description 1
- WPNFPRWHXVVLKV-UHFFFAOYSA-N 2-(2-piperidin-4-yloxyethyl)phenol Chemical compound OC1=CC=CC=C1CCOC1CCNCC1 WPNFPRWHXVVLKV-UHFFFAOYSA-N 0.000 description 1
- KNWAOWNYXRUCNP-UHFFFAOYSA-N 2-(2-piperidin-4-yloxyethyl)phenol;hydrochloride Chemical compound Cl.OC1=CC=CC=C1CCOC1CCNCC1 KNWAOWNYXRUCNP-UHFFFAOYSA-N 0.000 description 1
- VULUOYHJUMCHSH-UHFFFAOYSA-N 2-chloro-7-methoxy-6-phenylmethoxyquinazolin-4-amine Chemical compound COC1=CC2=NC(Cl)=NC(N)=C2C=C1OCC1=CC=CC=C1 VULUOYHJUMCHSH-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
- RMMHOFFPGKSRDI-UHFFFAOYSA-N 3-bromoprop-1-en-2-ylbenzene Chemical compound BrCC(=C)C1=CC=CC=C1 RMMHOFFPGKSRDI-UHFFFAOYSA-N 0.000 description 1
- OHCMRDCUBBBJJO-UHFFFAOYSA-N 4-[2-(2-ethoxyphenyl)ethoxy]piperidine;oxalic acid Chemical compound OC(=O)C(O)=O.CCOC1=CC=CC=C1CCOC1CCNCC1 OHCMRDCUBBBJJO-UHFFFAOYSA-N 0.000 description 1
- RTMVEYKTNQUBRW-UHFFFAOYSA-N 4-amino-2-[4-(2-ethoxy-1-phenylethoxy)piperidin-1-yl]-7-methoxyquinazolin-6-ol Chemical compound NC1=NC(=NC2=CC(=C(C=C12)O)OC)N1CCC(CC1)OC(COCC)C1=CC=CC=C1 RTMVEYKTNQUBRW-UHFFFAOYSA-N 0.000 description 1
- YXMFSSJMZIAGCI-UHFFFAOYSA-N 6-ethoxy-2-[4-(2-ethoxy-1-phenylethoxy)piperidin-1-yl]-7-methoxyquinazolin-4-amine Chemical compound NC1=NC(=NC2=CC(=C(C=C12)OCC)OC)N1CCC(CC1)OC(COCC)C1=CC=CC=C1 YXMFSSJMZIAGCI-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
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- SCENUOUAYLAIEO-UHFFFAOYSA-N Cl.NC1=NC(=NC2=CC(=C(C=C12)OCC1=CC=CC=C1)OC)N1CCC(CC1)OC(COCC)C1=CC=CC=C1 Chemical compound Cl.NC1=NC(=NC2=CC(=C(C=C12)OCC1=CC=CC=C1)OC)N1CCC(CC1)OC(COCC)C1=CC=CC=C1 SCENUOUAYLAIEO-UHFFFAOYSA-N 0.000 description 1
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- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 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
- 230000036772 blood pressure Effects 0.000 description 1
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- 229940001468 citrate Drugs 0.000 description 1
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- 238000007796 conventional method Methods 0.000 description 1
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- 229910000365 copper sulfate Inorganic materials 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
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 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
- 238000002156 mixing Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- OFCOQOUNYWWMDJ-UHFFFAOYSA-N n-(2-hexyl-4-oxoquinazolin-3-yl)-4-hydroxy-1-(2-methylpropyl)-2-oxo-5,6,7,8-tetrahydroquinoline-3-carboxamide Chemical compound C1CCCC(N(CC(C)C)C2=O)=C1C(O)=C2C(=O)NN1C(=O)C2=CC=CC=C2N=C1CCCCCC OFCOQOUNYWWMDJ-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 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 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 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
- 238000003756 stirring Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7903398 | 1979-01-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS60780A2 CS60780A2 (en) | 1984-01-16 |
| CS231970B2 true CS231970B2 (en) | 1985-01-16 |
Family
ID=10502852
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS80607A CS231970B2 (en) | 1979-01-31 | 1980-01-29 | Manufacturing process of the 4-amino-2-peperidinochinazoline derivatives |
Country Status (28)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2483920A1 (fr) * | 1980-06-09 | 1981-12-11 | Synthelabo | Nouveaux derives de quinazoline, leur procede de preparation et leur application en therapeutique |
| ES8405389A1 (es) * | 1981-09-09 | 1983-11-01 | Orion Yhtymae Oy | "metodo para la preparacion de piperidinilquinazolidinas substituidas". |
| US5280032A (en) * | 1989-02-14 | 1994-01-18 | Toyama Chemical Co., Ltd. | 1,2-ethanediol derivative and salt thereof, process for producing the same, and cerebral function-improving agent comprising the same |
| WO2013070852A2 (en) * | 2011-11-08 | 2013-05-16 | Emory University | Compounds and compositions used to epigenetically transform cells and methods related thereto |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1088068A (en) * | 1977-11-16 | 1980-10-21 | Simon F. Campbell | Piperidino-quinazolines |
| GB2021108B (en) * | 1978-05-18 | 1982-07-21 | Pfizer Ltd | 6,7 - di - 4 - amino - 2 - quinazolines |
-
1979
- 1979-01-30 IE IE800178A patent/IE800178L/xx unknown
- 1979-12-18 DK DK540879A patent/DK540879A/da not_active Application Discontinuation
-
1980
- 1980-01-28 PH PH23559A patent/PH15436A/en unknown
- 1980-01-29 NZ NZ192744A patent/NZ192744A/en unknown
- 1980-01-29 YU YU00229/80A patent/YU22980A/xx unknown
- 1980-01-29 IL IL59252A patent/IL59252A/xx unknown
- 1980-01-29 IT IT19537/80A patent/IT1149902B/it active
- 1980-01-29 AT AT0046980A patent/AT373595B/de not_active IP Right Cessation
- 1980-01-29 FI FI800252A patent/FI63936C/fi not_active IP Right Cessation
- 1980-01-29 SE SE8000699A patent/SE8000699L/xx not_active Application Discontinuation
- 1980-01-29 CS CS80607A patent/CS231970B2/cs unknown
- 1980-01-30 PT PT70749A patent/PT70749A/pt unknown
- 1980-01-30 PL PL1980221683A patent/PL121890B1/pl unknown
- 1980-01-30 HU HU80202A patent/HU184233B/hu unknown
- 1980-01-30 NL NL8000571A patent/NL8000571A/nl not_active Application Discontinuation
- 1980-01-30 NO NO800230A patent/NO800230L/no unknown
- 1980-01-30 CA CA344,714A patent/CA1131636A/en not_active Expired
- 1980-01-30 JP JP990580A patent/JPS55104278A/ja active Granted
- 1980-01-30 SU SU802877159A patent/SU895291A3/ru active
- 1980-01-30 BE BE0/199187A patent/BE881448A/fr not_active IP Right Cessation
- 1980-01-30 AR AR279793A patent/AR222208A1/es active
- 1980-01-30 ZA ZA00800557A patent/ZA80557B/xx unknown
- 1980-01-30 DE DE19803003323 patent/DE3003323A1/de not_active Ceased
- 1980-01-30 FR FR8002012A patent/FR2447919A1/fr active Granted
- 1980-01-31 LU LU82115A patent/LU82115A1/fr unknown
- 1980-01-31 DD DD80218769A patent/DD148720A5/de unknown
- 1980-01-31 ES ES488129A patent/ES8101583A1/es not_active Expired
- 1980-02-11 GR GR61081A patent/GR73626B/el unknown
Also Published As
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