CA1262353A - Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs - Google Patents

Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs

Info

Publication number: CA1262353A
Authority: CA; Canada
Prior art keywords: phenyl; compound; alkyl; formula; alk1
Prior art date: 1984-04-06
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000574154A

Other languages

English (en)

Inventor

Young S. Lo

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

AH Robins Co Inc

Original Assignee

AH Robins Co Inc

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.)

1984-04-06

Filing date

1988-08-08

Publication date

1989-10-17

1984-04-06 Priority claimed from US06/597,413 external-priority patent/US4560510A/en

1988-08-08 Application filed by AH Robins Co Inc filed Critical AH Robins Co Inc

1988-08-08 Priority to CA000574154A priority Critical patent/CA1262353A/fr

1989-10-17 Application granted granted Critical

1989-10-17 Publication of CA1262353A publication Critical patent/CA1262353A/fr

Status Expired legal-status Critical Current

Links

239000000543 intermediate Substances 0.000 title abstract description 16
239000000935 antidepressant agent Substances 0.000 title abstract description 9
230000001430 anti-depressive effect Effects 0.000 title abstract description 8
229940005513 antidepressants Drugs 0.000 title abstract description 7
OPACCTXYZFTUOQ-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,4]benzodiazepine Chemical class N1C=CN=CC2=CC=C(N=CC=C3)C3=C12 OPACCTXYZFTUOQ-UHFFFAOYSA-N 0.000 title abstract description 4
150000008365 aromatic ketones Chemical class 0.000 title abstract 3
238000002360 preparation method Methods 0.000 title description 19
-1 tetrahydropyranyloxy Chemical group 0.000 claims abstract description 38
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
239000001257 hydrogen Substances 0.000 claims abstract description 27
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
150000002431 hydrogen Chemical class 0.000 claims abstract description 13
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
229910052736 halogen Inorganic materials 0.000 claims abstract description 10
150000002367 halogens Chemical class 0.000 claims abstract description 10
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims abstract description 9
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 7
125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
125000001424 substituent group Chemical group 0.000 claims abstract 3
150000001875 compounds Chemical class 0.000 claims description 96
238000000034 method Methods 0.000 claims description 46
239000002253 acid Substances 0.000 claims description 27
150000003839 salts Chemical class 0.000 claims description 24
238000006243 chemical reaction Methods 0.000 claims description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 15
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 9
NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 claims description 8
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
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 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 8
LHMLYBNZHMOMOY-UHFFFAOYSA-N [2-[3-(dimethylamino)propylamino]phenyl]-phenylmethanone Chemical compound CN(C)CCCNC1=CC=CC=C1C(=O)C1=CC=CC=C1 LHMLYBNZHMOMOY-UHFFFAOYSA-N 0.000 claims 3
125000000068 chlorophenyl group Chemical group 0.000 claims 2
125000001207 fluorophenyl group Chemical group 0.000 claims 2
150000003868 ammonium compounds Chemical class 0.000 claims 1
150000003856 quaternary ammonium compounds Chemical class 0.000 claims 1
229940049706 benzodiazepine Drugs 0.000 abstract description 25
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 17
229910052783 alkali metal Inorganic materials 0.000 abstract description 10
150000001557 benzodiazepines Chemical class 0.000 abstract description 9
150000001340 alkali metals Chemical group 0.000 abstract description 6
125000000217 alkyl group Chemical group 0.000 abstract description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 2
125000001475 halogen functional group Chemical group 0.000 abstract description 2
125000004076 pyridyl group Chemical group 0.000 abstract description 2
125000003545 alkoxy group Chemical group 0.000 abstract 1
125000001544 thienyl group Chemical group 0.000 abstract 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 144
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
239000000203 mixture Substances 0.000 description 47
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
239000000047 product Substances 0.000 description 31
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
239000010410 layer Substances 0.000 description 26
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 21
239000012312 sodium hydride Substances 0.000 description 21
229910000104 sodium hydride Inorganic materials 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 20
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 19
239000002585 base Substances 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 16
239000000126 substance Substances 0.000 description 15
MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 14
239000007788 liquid Substances 0.000 description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
239000002904 solvent Substances 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000000460 chlorine Substances 0.000 description 12
238000010992 reflux Methods 0.000 description 12
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
230000000269 nucleophilic effect Effects 0.000 description 11
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical group [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
239000003153 chemical reaction reagent Substances 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
239000000376 reactant Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
239000002002 slurry Substances 0.000 description 8
239000007787 solid Substances 0.000 description 8
CJHKJXZMFZKGHI-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,2]benzodiazepine Chemical class N1N=CC=CC2=CC=C(N=CC=C3)C3=C12 CJHKJXZMFZKGHI-UHFFFAOYSA-N 0.000 description 7
125000003118 aryl group Chemical group 0.000 description 7
239000000969 carrier Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 7
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 7
239000007858 starting material Substances 0.000 description 7
239000006188 syrup Substances 0.000 description 7
235000020357 syrup Nutrition 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
229910001413 alkali metal ion Inorganic materials 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
229910052731 fluorine Inorganic materials 0.000 description 6
239000012458 free base Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000000725 suspension Substances 0.000 description 6
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
125000004356 hydroxy functional group Chemical group O* 0.000 description 5
239000002480 mineral oil Substances 0.000 description 5
235000010446 mineral oil Nutrition 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
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 description 4
150000007513 acids Chemical class 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
239000001530 fumaric acid Substances 0.000 description 4
150000002430 hydrocarbons Chemical group 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
159000000000 sodium salts Chemical class 0.000 description 4
238000001228 spectrum Methods 0.000 description 4
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
229940126062 Compound A Drugs 0.000 description 3
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
239000012535 impurity Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
125000000719 pyrrolidinyl group Chemical group 0.000 description 3
150000003335 secondary amines Chemical class 0.000 description 3
238000003756 stirring Methods 0.000 description 3
PELAWRHVRDOWQT-UHFFFAOYSA-N (2-amino-4-chlorophenyl)-phenylmethanone Chemical compound NC1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1 PELAWRHVRDOWQT-UHFFFAOYSA-N 0.000 description 2
WEWXXYDHYCDEKY-UHFFFAOYSA-N (2-aminophenyl)-pyridin-2-ylmethanone Chemical group NC1=CC=CC=C1C(=O)C1=CC=CC=N1 WEWXXYDHYCDEKY-UHFFFAOYSA-N 0.000 description 2
MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 2
PERYPNLSKBMHJJ-TYYBGVCCSA-N (e)-but-2-enedioic acid;propan-1-amine Chemical compound CCCN.OC(=O)\C=C\C(O)=O PERYPNLSKBMHJJ-TYYBGVCCSA-N 0.000 description 2
VODXGLYUVHXTQC-UHFFFAOYSA-N 3-chloropropyl 2h-pyran-2-carboxylate Chemical compound ClCCCOC(=O)C1OC=CC=C1 VODXGLYUVHXTQC-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
241001024304 Mino Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
238000000451 chemical ionisation Methods 0.000 description 2
150000001805 chlorine compounds Chemical group 0.000 description 2
235000008504 concentrate Nutrition 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
AVGAIPMGSIOHFZ-UHFFFAOYSA-N dichloromethane;2-propan-2-yloxypropane Chemical compound ClCCl.CC(C)OC(C)C AVGAIPMGSIOHFZ-UHFFFAOYSA-N 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
238000001035 drying Methods 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
210000003918 fraction a Anatomy 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000010354 integration Effects 0.000 description 2
239000011630 iodine Substances 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000008188 pellet Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
239000003586 protic polar solvent Substances 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229960005333 tetrabenazine Drugs 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
239000010936 titanium Substances 0.000 description 2
229910052719 titanium Inorganic materials 0.000 description 2
125000003944 tolyl group Chemical group 0.000 description 2
GFHWOKUXKUUKQJ-UHFFFAOYSA-N (2-amino-4-methoxyphenyl)-phenylmethanone Chemical compound NC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 GFHWOKUXKUUKQJ-UHFFFAOYSA-N 0.000 description 1
YINYAGBOKBLJHY-UHFFFAOYSA-N (2-amino-4-methylphenyl)-phenylmethanone Chemical compound NC1=CC(C)=CC=C1C(=O)C1=CC=CC=C1 YINYAGBOKBLJHY-UHFFFAOYSA-N 0.000 description 1
MPNFILXHGOVCKS-UHFFFAOYSA-N (2-amino-4-nitrophenyl)-phenylmethanone Chemical compound NC1=CC([N+]([O-])=O)=CC=C1C(=O)C1=CC=CC=C1 MPNFILXHGOVCKS-UHFFFAOYSA-N 0.000 description 1
ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 1
RMMJUQSANCPTMV-UHFFFAOYSA-N (2-aminophenyl)-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=CC=C1N RMMJUQSANCPTMV-UHFFFAOYSA-N 0.000 description 1
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LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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239000008096 xylene Substances 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000574154A 1984-04-06 1988-08-08 Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs Expired CA1262353A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000574154A CA1262353A (fr)	1984-04-06	1988-08-08	Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US06/597,413 US4560510A (en)	1984-04-06	1984-04-06	Process and intermediates for the preparation of aryl substituted pyrido[1,4]benzodiazepines
US597,413		1984-04-06
CA000478110A CA1255301A (fr)	1984-04-06	1985-04-02	Methode et produits intermediaires pour la preparation de derives de substitution aryles de pyrido[1,4]benzodiazepines
CA000574154A CA1262353A (fr)	1984-04-06	1988-08-08	Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000478110A Division CA1255301A (fr)	1984-04-06	1985-04-02	Methode et produits intermediaires pour la preparation de derives de substitution aryles de pyrido[1,4]benzodiazepines

Publications (1)

Publication Number	Publication Date
CA1262353A true CA1262353A (fr)	1989-10-17

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Application Number	Title	Priority Date	Filing Date
CA000574154A Expired CA1262353A (fr)	1984-04-06	1988-08-08	Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs

Country Status (1)

Country	Link
CA (1)	CA1262353A (fr)

1988
- 1988-08-08 CA CA000574154A patent/CA1262353A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1992-04-19	MKLA	Lapsed

Publication	Publication Date	Title
CA1248532A (fr)	1989-01-10	Derives de pyrazolo¬3,4-b\|pyridine; methode de preparation
AU644295B2 (en)	1993-12-02	2-aminopyrimidine-4-carboxamide derivatives, their preparation and their use in therapeutics
NO172490B (no)	1993-04-19	Analogifremgangsmaate for fremstilling av terapeutisk aktive 1,4-disubstituerte piperazinderivater
CA1262353A (fr)	1989-10-17	Derives de cetone aromatique, produits intermediaires pour la preparation de pyrido[1,4] benzodiazepines, antidepresseurs
US4560510A (en)	1985-12-24	Process and intermediates for the preparation of aryl substituted pyrido[1,4]benzodiazepines
US4447361A (en)	1984-05-08	Aryl substituted pyrido[1,4]benzodiazepines
WO1998042708A2 (fr)	1998-10-01	Amines tricycliques pharmaceutiquement actives
US4129738A (en)	1978-12-12	5-Phenylpyrazolo[1,5-a]pyrimidin-7(1H)-ones
CA1175048A (fr)	1984-09-25	Esters derives de l'acide 2-cyclique amino-2-(1,2- benzisoxazol-3-yl)-acetique
KR870000279B1 (ko)	1987-02-23	피리도 [1,4] 벤조디아제핀 및 [2-[(니트로피리디닐) 아미노]페닐] 아릴메타논의 제조방법
Kökösi et al.	1982	Nitrogen bridgehead compounds. Part 19. Synthesis of polymethylenepyrimidin‐4‐ones
US4628100A (en)	1986-12-09	Intermediates for the preparation of aryl substituted pyrido[1,4]benzodiazepines
Petigara et al.	1974	Novel polycyclic heterocycles. XI. Synthesis of 11, 12‐dihydropyrido [2, 1‐b][1, 3] benzodiazepines, 6H‐pyrido [1, 2‐c][1, 3, 5] benzoxadiazepines, and 6H‐Pyrido [1, 2‐c][1, 3, 5] benzothiadiazepines
WO2000006575A2 (fr)	2000-02-10	Nouveaux composes
CA1198424A (fr)	1985-12-24	Nitro, amino et aroylamino-n-phenylpyridinamines dans le procede pour preparer les pyrido ¬1,4\| benzodiazepines
EP0743946A1 (fr)	1996-11-27	Indoles condenses a titre d'antagonistes des recepteurs de 5ht 2b?
SU999967A3 (ru)	1983-02-23	Способ получени 6-N-замещенных 6-амино-3-пиридазинилгидразинов или их солей
Muller et al.	1982	Regioselective Synthesis of 2‐oxo‐2, 8‐dihydro‐[l, 2, 4] oxadiazolo [2, 3‐a] pyrimidine‐7‐carbamates: A New Class of Antihypertensive Peripheral Vasodilators
CA2028953A1 (fr)	1990-10-22	Procede pour la preparation de derives quinazoline
EP0076017B1 (fr)	1990-08-16	Pyrido(1,4)benzodiazépines substituées par un phényl et intermédiaires
Aubert et al.	1989	Synthesis of dipyrazolo [3, 4-b: 4′, 3′-f] azepines and dithieno [2, 3-b: 3′, 2′ f] azepines from 1-substituted 2, 7-dichloro-4, 5-dihydro-1 H-azepine-3, 6-dicarbaldehydes
YAMANAKA et al.	1979	Studies on Quinoline and Isoquinoline Derivatives. IV. Reaction of Quinoline and Isoquinoline N-Oxides with 3-Amino-crotononitrile and Related Compounds
US4518603A (en)	1985-05-21	[2-[(Nitropyridinyl)amino]phenyl]arylmethanones in a process for preparing pyrido[1,4]benzodiazepines
CA1199324A (fr)	1986-01-14	Derives de substitution phenyles de pyrido¬1,4\| benzodiazepines, et produits intermediaires
US4495183A (en)	1985-01-22	Aryl substituted pyrido[1,4]benzodiazepines for treatment of depression