NL8200549A - Door een fenylgroep gesubstitueerde pyrido1,4benzodiazepinen en tussenprodukten daarvoor. - Google Patents
Door een fenylgroep gesubstitueerde pyrido1,4benzodiazepinen en tussenprodukten daarvoor. Download PDFInfo
- Publication number
- NL8200549A NL8200549A NL8200549A NL8200549A NL8200549A NL 8200549 A NL8200549 A NL 8200549A NL 8200549 A NL8200549 A NL 8200549A NL 8200549 A NL8200549 A NL 8200549A NL 8200549 A NL8200549 A NL 8200549A
- Authority
- NL
- Netherlands
- Prior art keywords
- pyrido
- phenyl
- benzodiazepine
- amino
- compound according
- Prior art date
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- -1 PHENYL GROUP Chemical group 0.000 title claims description 123
- 239000000543 intermediate Substances 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims description 163
- 239000000203 mixture Substances 0.000 claims description 106
- 229940049706 benzodiazepine Drugs 0.000 claims description 85
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 66
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 64
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
- 229910052757 nitrogen Inorganic materials 0.000 claims description 61
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 50
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 47
- 239000000047 product Substances 0.000 claims description 38
- 238000002360 preparation method Methods 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 29
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 17
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 claims description 16
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 239000007858 starting material Substances 0.000 claims description 11
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 10
- CJHKJXZMFZKGHI-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,2]benzodiazepine Chemical compound N1N=CC=CC2=CC=C(N=CC=C3)C3=C12 CJHKJXZMFZKGHI-UHFFFAOYSA-N 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 150000001557 benzodiazepines Chemical class 0.000 claims description 8
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- AFMGAVDATRJOJG-GUYCJALGSA-N (3s,5s)-3-methyl-5-[(4-phenylphenyl)methyl]pyrrolidin-2-one Chemical compound N1C(=O)[C@@H](C)C[C@H]1CC1=CC=C(C=2C=CC=CC=2)C=C1 AFMGAVDATRJOJG-GUYCJALGSA-N 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- 230000001430 anti-depressive effect Effects 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000000935 antidepressant agent Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
- XDSFEVFCNJALNV-WLHGVMLRSA-N 1h-1,2-benzodiazepine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.N1N=CC=CC2=CC=CC=C12 XDSFEVFCNJALNV-WLHGVMLRSA-N 0.000 claims description 3
- WQOTZBOEOBUZRP-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-3-chlorophenyl]-phenylmethanone Chemical compound NC1=CC=CN=C1NC1=C(Cl)C=CC=C1C(=O)C1=CC=CC=C1 WQOTZBOEOBUZRP-UHFFFAOYSA-N 0.000 claims description 3
- ALNYFJCONXXPNA-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(4-fluorophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=C(F)C=C1 ALNYFJCONXXPNA-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- UUBJKHVFGWGJKX-UHFFFAOYSA-N hydrate tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl UUBJKHVFGWGJKX-UHFFFAOYSA-N 0.000 claims description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
- 125000005544 phthalimido group Chemical group 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical class [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 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 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 3
- DTSZGOYWJREPIZ-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]-5-chlorophenyl]-(2-chlorophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl DTSZGOYWJREPIZ-UHFFFAOYSA-N 0.000 claims description 2
- HGZDETKBNOINJD-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-(2-bromophenyl)methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=CC=C1Br HGZDETKBNOINJD-UHFFFAOYSA-N 0.000 claims description 2
- MHKLFRMMDOUFTE-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-[3-(trifluoromethyl)phenyl]methanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=CC(C(F)(F)F)=C1 MHKLFRMMDOUFTE-UHFFFAOYSA-N 0.000 claims description 2
- JKOYHSGPAKBGAG-UHFFFAOYSA-N [2-[(3-aminopyridin-2-yl)amino]phenyl]-phenylmethanone Chemical compound NC1=CC=CN=C1NC1=CC=CC=C1C(=O)C1=CC=CC=C1 JKOYHSGPAKBGAG-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 125000005265 dialkylamine group Chemical group 0.000 claims description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 3
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000000654 additive Substances 0.000 claims 2
- 230000000996 additive effect Effects 0.000 claims 2
- 239000007795 chemical reaction product Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 claims 1
- KZTSPJVDGPAZQN-UHFFFAOYSA-N C1(=CC=CC=C1)C1=CC2=C(NC3=C1C=CC=C3)N=CC=C2 Chemical group C1(=CC=CC=C1)C1=CC2=C(NC3=C1C=CC=C3)N=CC=C2 KZTSPJVDGPAZQN-UHFFFAOYSA-N 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 258
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 102
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 56
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000000243 solution Substances 0.000 description 52
- 238000004458 analytical method Methods 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 33
- 239000007787 solid Substances 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 239000000284 extract Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 26
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 23
- 239000012312 sodium hydride Substances 0.000 description 23
- 229910000104 sodium hydride Inorganic materials 0.000 description 23
- 239000000725 suspension Substances 0.000 description 23
- 239000012458 free base Substances 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- 239000012299 nitrogen atmosphere Substances 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 15
- LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 14
- 230000008018 melting Effects 0.000 description 14
- 238000002844 melting Methods 0.000 description 14
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 13
- 239000013543 active substance Substances 0.000 description 13
- 239000002480 mineral oil Substances 0.000 description 12
- 235000010446 mineral oil Nutrition 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- 239000002775 capsule Substances 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000001035 drying Methods 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 239000001530 fumaric acid Substances 0.000 description 9
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 9
- 229910052753 mercury Inorganic materials 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
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- 239000000126 substance Substances 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 5
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 5
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- WUFWBVLAMURTLR-UHFFFAOYSA-N 6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine Chemical compound N=1C2=CC=CN=C2NC2=CC=CC=C2C=1C1=CC=CC=C1 WUFWBVLAMURTLR-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
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- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 4
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- 230000002378 acidificating effect Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- UFKDESIUZHMUGL-UHFFFAOYSA-N boron;formonitrile;sodium Chemical compound [B].[Na].N#C UFKDESIUZHMUGL-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 4
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- 238000010438 heat treatment Methods 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
- RZJPBQGRCNJYBU-UHFFFAOYSA-N 3-chloropyridin-2-amine Chemical compound NC1=NC=CC=C1Cl RZJPBQGRCNJYBU-UHFFFAOYSA-N 0.000 description 3
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000000451 chemical ionisation Methods 0.000 description 3
- 150000008533 dibenzodiazepines Chemical class 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
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- 238000002955 isolation Methods 0.000 description 3
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- 239000003960 organic solvent Substances 0.000 description 3
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
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- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30508081A | 1981-09-24 | 1981-09-24 | |
| US30508081 | 1981-09-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8200549A true NL8200549A (nl) | 1983-04-18 |
Family
ID=23179241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8200549A NL8200549A (nl) | 1981-09-24 | 1982-02-12 | Door een fenylgroep gesubstitueerde pyrido1,4benzodiazepinen en tussenprodukten daarvoor. |
Country Status (27)
| Country | Link |
|---|---|
| JP (1) | JPS5865290A (fr) |
| KR (1) | KR890000764B1 (fr) |
| BE (1) | BE891666A (fr) |
| CA (1) | CA1199324A (fr) |
| CH (1) | CH651833A5 (fr) |
| DE (1) | DE3150522A1 (fr) |
| DK (3) | DK186282A (fr) |
| EG (1) | EG15904A (fr) |
| ES (6) | ES507971A0 (fr) |
| FI (1) | FI71935C (fr) |
| FR (1) | FR2515183B1 (fr) |
| GR (1) | GR78473B (fr) |
| HU (2) | HU189426B (fr) |
| IE (1) | IE52493B1 (fr) |
| IL (1) | IL64284A (fr) |
| IN (1) | IN156080B (fr) |
| IT (1) | IT1146728B (fr) |
| LU (1) | LU83865A1 (fr) |
| NL (1) | NL8200549A (fr) |
| NO (1) | NO157700C (fr) |
| NZ (1) | NZ198999A (fr) |
| PH (2) | PH17847A (fr) |
| PL (6) | PL143322B1 (fr) |
| PT (1) | PT74286B (fr) |
| SE (2) | SE448629B (fr) |
| YU (1) | YU46128B (fr) |
| ZA (1) | ZA817866B (fr) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3825549A (en) * | 1972-10-24 | 1974-07-23 | Squibb & Sons Inc | Certain dihydropyrido(2,1-b)(1,3)benzodi-azepines and benzodiazocines |
| DE2424811C3 (de) * | 1974-05-22 | 1981-08-20 | Dr. Karl Thomae Gmbh, 7950 Biberach | Pyrido-benzodiazepinone, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| SE422799B (sv) * | 1975-05-28 | 1982-03-29 | Merck & Co Inc | Analogiforfarande for framstellning av 1,3-dihydroimidazo (4,5-b)pyridin-2-oner |
-
1981
- 1981-11-05 SE SE8106573A patent/SE448629B/sv not_active IP Right Cessation
- 1981-11-12 NO NO813839A patent/NO157700C/no unknown
- 1981-11-12 ZA ZA817866A patent/ZA817866B/xx unknown
- 1981-11-13 IL IL64284A patent/IL64284A/xx unknown
- 1981-11-13 IN IN1261/CAL/81A patent/IN156080B/en unknown
- 1981-11-17 GR GR66553A patent/GR78473B/el unknown
- 1981-11-18 PH PH26507A patent/PH17847A/en unknown
- 1981-11-25 IE IE2769/81A patent/IE52493B1/en unknown
- 1981-12-09 IT IT68605/81A patent/IT1146728B/it active
- 1981-12-10 FI FI813976A patent/FI71935C/fi not_active IP Right Cessation
- 1981-12-15 ES ES507971A patent/ES507971A0/es active Granted
- 1981-12-15 HU HU843212A patent/HU189426B/hu not_active IP Right Cessation
- 1981-12-15 HU HU813777A patent/HU187393B/hu not_active IP Right Cessation
- 1981-12-21 DE DE19813150522 patent/DE3150522A1/de not_active Withdrawn
- 1981-12-23 PL PL1981253540A patent/PL143322B1/pl unknown
- 1981-12-23 PL PL1981234426A patent/PL138859B1/pl unknown
- 1981-12-23 PL PL1981253539A patent/PL143597B1/pl unknown
- 1981-12-23 PL PL1981241409A patent/PL139381B1/pl unknown
- 1981-12-23 FR FR8124111A patent/FR2515183B1/fr not_active Expired
- 1981-12-23 PL PL1981241410A patent/PL137068B1/pl unknown
- 1981-12-23 PL PL1981253538A patent/PL143596B1/pl unknown
- 1981-12-30 BE BE0/206969A patent/BE891666A/fr not_active IP Right Cessation
-
1982
- 1982-01-05 LU LU83865A patent/LU83865A1/fr unknown
- 1982-01-12 EG EG11/82A patent/EG15904A/xx active
- 1982-01-14 JP JP57004813A patent/JPS5865290A/ja active Pending
- 1982-01-15 PT PT74286A patent/PT74286B/pt unknown
- 1982-01-18 CA CA000394367A patent/CA1199324A/fr not_active Expired
- 1982-02-02 KR KR8200420A patent/KR890000764B1/ko not_active Expired
- 1982-02-12 NL NL8200549A patent/NL8200549A/nl not_active Application Discontinuation
- 1982-02-18 NZ NZ198999A patent/NZ198999A/en unknown
- 1982-03-23 YU YU62582A patent/YU46128B/sh unknown
- 1982-04-15 CH CH2288/82A patent/CH651833A5/fr not_active IP Right Cessation
- 1982-04-26 DK DK186282A patent/DK186282A/da not_active Application Discontinuation
- 1982-09-29 ES ES516052A patent/ES516052A0/es active Granted
- 1982-09-29 ES ES516051A patent/ES516051A0/es active Granted
-
1983
- 1983-10-19 ES ES526563A patent/ES8604531A1/es not_active Expired
- 1983-10-19 ES ES526562A patent/ES526562A0/es active Granted
-
1984
- 1984-08-17 PH PH31120A patent/PH20536A/en unknown
-
1985
- 1985-05-21 ES ES543328A patent/ES8607726A1/es not_active Expired
-
1986
- 1986-02-17 SE SE8600688A patent/SE455305B/sv not_active IP Right Cessation
-
1987
- 1987-08-03 DK DK403387A patent/DK403387A/da not_active Application Discontinuation
- 1987-08-03 DK DK403487A patent/DK403487A/da not_active Application Discontinuation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A85 | Still pending on 85-01-01 | ||
| BA | A request for search or an international-type search has been filed | ||
| BB | A search report has been drawn up | ||
| BC | A request for examination has been filed | ||
| BV | The patent application has lapsed |