CA1101860A - Traduction non-disponible - Google Patents

Traduction non-disponible

Info

Publication number: CA1101860A
Authority: CA; Canada
Prior art keywords: hydrogen; methyl; carbon atoms; ether; hydroxy
Prior art date: 1976-05-17
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

CA344,747A

Other languages

English (en)

Inventor

Michael R. Johnson

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.)

Pfizer Corp SRL

Original Assignee

Pfizer Corp SRL

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.)

1976-05-17

Filing date

1980-02-25

Publication date

1981-05-26

1977-05-13 Priority claimed from CA278,410A external-priority patent/CA1095909A/fr

1980-02-25 Application filed by Pfizer Corp SRL filed Critical Pfizer Corp SRL

1980-02-25 Priority to CA344,747A priority Critical patent/CA1101860A/fr

1981-05-26 Application granted granted Critical

1981-05-26 Publication of CA1101860A publication Critical patent/CA1101860A/fr

Status Expired legal-status Critical Current

Links

239000000543 intermediate Substances 0.000 title abstract description 8
238000004519 manufacturing process Methods 0.000 title abstract description 4
239000003814 drug Substances 0.000 title description 14
JBHCHNYONQSXLP-UHFFFAOYSA-N 1,2,3,4-tetrahydrophenanthridine Chemical compound N1=CC2=CC=CC=C2C2=C1CCCC2 JBHCHNYONQSXLP-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 142
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 88
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 74
239000001257 hydrogen Substances 0.000 claims abstract description 70
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 39
-1 pyrrolo Chemical group 0.000 claims abstract description 38
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 36
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 36
125000000217 alkyl group Chemical group 0.000 claims abstract description 33
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 24
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
125000002947 alkylene group Chemical group 0.000 claims abstract description 15
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims abstract description 12
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 10
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 10
229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
125000002252 acyl group Chemical group 0.000 claims abstract description 8
125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 7
229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 3
150000002431 hydrogen Chemical group 0.000 claims abstract 16
125000001589 carboacyl group Chemical group 0.000 claims abstract 4
125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract 2
125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract 2
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 abstract 2
125000004076 pyridyl group Chemical group 0.000 claims abstract 2
238000000034 method Methods 0.000 claims description 59
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
230000008569 process Effects 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 9
238000005907 ketalization reaction Methods 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims 1
125000005605 benzo group Chemical class 0.000 abstract description 54
239000003795 chemical substances by application Substances 0.000 abstract description 19
229960005419 nitrogen Drugs 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 218
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 142
239000000203 mixture Substances 0.000 description 119
239000003921 oil Substances 0.000 description 111
235000019198 oils Nutrition 0.000 description 111
239000000243 solution Substances 0.000 description 111
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 107
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
239000000047 product Substances 0.000 description 69
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 67
238000006243 chemical reaction Methods 0.000 description 67
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
239000011541 reaction mixture Substances 0.000 description 52
229940093499 ethyl acetate Drugs 0.000 description 47
235000019439 ethyl acetate Nutrition 0.000 description 47
125000003118 aryl group Chemical group 0.000 description 41
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
239000002253 acid Substances 0.000 description 37
238000004458 analytical method Methods 0.000 description 37
239000000284 extract Substances 0.000 description 35
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 34
239000000741 silica gel Substances 0.000 description 34
229910002027 silica gel Inorganic materials 0.000 description 34
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 28
239000012267 brine Substances 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 28
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
101150041968 CDC13 gene Proteins 0.000 description 26
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
239000007787 solid Substances 0.000 description 26
229960000583 acetic acid Drugs 0.000 description 25
230000000875 corresponding effect Effects 0.000 description 25
239000010410 layer Substances 0.000 description 25
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
229940073584 methylene chloride Drugs 0.000 description 24
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 20
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 19
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
229910000041 hydrogen chloride Inorganic materials 0.000 description 18
238000003756 stirring Methods 0.000 description 18
235000011167 hydrochloric acid Nutrition 0.000 description 17
229960000443 hydrochloric acid Drugs 0.000 description 17
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 17
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
238000011282 treatment Methods 0.000 description 17
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 16
150000002148 esters Chemical class 0.000 description 16
125000006239 protecting group Chemical group 0.000 description 16
239000002904 solvent Substances 0.000 description 16
238000012360 testing method Methods 0.000 description 16
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
239000012299 nitrogen atmosphere Substances 0.000 description 15
150000003839 salts Chemical class 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 14
239000000376 reactant Substances 0.000 description 14
238000001953 recrystallisation Methods 0.000 description 14
238000010992 reflux Methods 0.000 description 14
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 13
239000005977 Ethylene Substances 0.000 description 13
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 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
229940079593 drug Drugs 0.000 description 12
239000003208 petroleum Substances 0.000 description 12
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
229960001701 chloroform Drugs 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
238000001704 evaporation Methods 0.000 description 11
230000008020 evaporation Effects 0.000 description 11
150000002500 ions Chemical class 0.000 description 11
229910052708 sodium Inorganic materials 0.000 description 11
239000011734 sodium Substances 0.000 description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
230000000694 effects Effects 0.000 description 10
239000000499 gel Substances 0.000 description 10
229910000027 potassium carbonate Inorganic materials 0.000 description 10
229940093956 potassium carbonate Drugs 0.000 description 10
235000011181 potassium carbonates Nutrition 0.000 description 10
230000009467 reduction Effects 0.000 description 10
238000006722 reduction reaction Methods 0.000 description 10
239000012279 sodium borohydride Substances 0.000 description 10
229910000033 sodium borohydride Inorganic materials 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
239000002585 base Substances 0.000 description 9
239000006227 byproduct Substances 0.000 description 9
230000003197 catalytic effect Effects 0.000 description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
239000000725 suspension Substances 0.000 description 9
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
229940022663 acetate Drugs 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
239000012043 crude product Substances 0.000 description 8
239000012259 ether extract Substances 0.000 description 8
238000001914 filtration Methods 0.000 description 8
239000012362 glacial acetic acid Substances 0.000 description 8
239000005457 ice water Substances 0.000 description 8
150000002576 ketones Chemical class 0.000 description 8
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 8
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 8
239000012071 phase Substances 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000012312 sodium hydride Substances 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
125000001424 substituent group Chemical group 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
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 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
229910052799 carbon Inorganic materials 0.000 description 7
239000003610 charcoal Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
238000010828 elution Methods 0.000 description 7
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 7
229910052744 lithium Inorganic materials 0.000 description 7
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
UYEMGAFJOZZIFP-UHFFFAOYSA-N 3,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC(O)=C1 UYEMGAFJOZZIFP-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
241001535291 Analges Species 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
WPUJEWVVTKLMQI-UHFFFAOYSA-N benzene;ethoxyethane Chemical compound CCOCC.C1=CC=CC=C1 WPUJEWVVTKLMQI-UHFFFAOYSA-N 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 6
239000006260 foam Substances 0.000 description 6
150000004678 hydrides Chemical class 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 6
239000011777 magnesium Substances 0.000 description 6
229910052700 potassium Inorganic materials 0.000 description 6
239000011591 potassium Substances 0.000 description 6
235000007686 potassium Nutrition 0.000 description 6
229960003975 potassium Drugs 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
101100347605 Arabidopsis thaliana VIII-A gene Proteins 0.000 description 5
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
241000699666 Mus <mouse, genus> Species 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
150000001335 aliphatic alkanes Chemical class 0.000 description 5
150000001448 anilines Chemical class 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000013078 crystal Substances 0.000 description 5
DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 5
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 5
238000000605 extraction Methods 0.000 description 5
229910052749 magnesium Inorganic materials 0.000 description 5
239000000463 material Substances 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-UHFFFAOYSA-N 0.000 description 4
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
230000009102 absorption Effects 0.000 description 4
238000010521 absorption reaction Methods 0.000 description 4
MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
229940111121 antirheumatic drug quinolines Drugs 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 4
MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 4
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
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WHRCPEPHXMEFGL-UHFFFAOYSA-N methyl 3-(3,5-dimethoxyanilino)propanoate Chemical compound COC(=O)CCNC1=CC(OC)=CC(OC)=C1 WHRCPEPHXMEFGL-UHFFFAOYSA-N 0.000 description 1
XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
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210000004080 milk Anatomy 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
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238000002156 mixing Methods 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
230000037023 motor activity Effects 0.000 description 1
APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 description 1
AEQFYBLGRSASMX-UHFFFAOYSA-N n-[3-phenylmethoxy-5-(5-phenylpentan-2-yl)phenyl]acetamide Chemical compound C=1C(NC(C)=O)=CC(OCC=2C=CC=CC=2)=CC=1C(C)CCCC1=CC=CC=C1 AEQFYBLGRSASMX-UHFFFAOYSA-N 0.000 description 1
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
125000001979 organolithium group Chemical group 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
150000004880 oxines Chemical class 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000006187 pill Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
229930010796 primary metabolite Natural products 0.000 description 1
230000005588 protonation Effects 0.000 description 1
230000000506 psychotropic effect Effects 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
238000005956 quaternization reaction Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
235000002020 sage Nutrition 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
241000894007 species Species 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000010959 steel Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
230000002311 subsequent effect Effects 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
230000001629 suppression Effects 0.000 description 1
208000006379 syphilis Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
229960002494 tetracaine hydrochloride Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
229940125725 tranquilizer Drugs 0.000 description 1
CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical class Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA344,747A 1976-05-17 1980-02-25 Traduction non-disponible Expired CA1101860A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA344,747A CA1101860A (fr)	1976-05-17	1980-02-25	Traduction non-disponible

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
US68733276A	1976-05-17	1976-05-17
US687,332		1976-05-17
US75361976A	1976-12-22	1976-12-22
US753,619		1976-12-22
US77792877A	1977-03-15	1977-03-15
CA278,410A CA1095909A (fr)	1976-05-17	1977-05-13	9-hydroxyhexahydrobenzol ¬c\| quinolines et intermediaires
CA344,747A CA1101860A (fr)	1976-05-17	1980-02-25	Traduction non-disponible
US777,928		1985-09-19

Publications (1)

Publication Number	Publication Date
CA1101860A true CA1101860A (fr)	1981-05-26

Family

ID=27508091

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA344,747A Expired CA1101860A (fr)	1976-05-17	1980-02-25	Traduction non-disponible

Country Status (1)

Country	Link
CA (1)	CA1101860A (fr)

1980
- 1980-02-25 CA CA344,747A patent/CA1101860A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1998-05-26	MKEX	Expiry

Publication	Publication Date	Title
US4260764A (en)	1981-04-07	9-Hydroxyoctahydrobenzo [C] quinolines and intermediates therefor
US5869672A (en)	1999-02-09	Huperzine A and analogs thereof
EP0045171B1 (fr)	1985-02-13	Amino-9 hydroxy-1 octahydrobenzo(c)quinoléines et leurs derivés
US4206225A (en)	1980-06-03	2,10-Disubstituted dibenzo[b,d]pyrans and benzo[c]quinolines
HU194858B (en)	1988-03-28	Process for producing dibenzo/b,d/pirane derivatives and pharmaceutical compositions containing them
EP0460062A1 (fr)	1991-12-11	Procede de synthese de l'huperzine a et ses analogues, et composes utiles dans cette synthese
CA1095909A (fr)	1981-02-17	9-hydroxyhexahydrobenzol ¬c\| quinolines et intermediaires
US4405626A (en)	1983-09-20	9-Hydroxyoctahydrobenzo(c)quinolines analgesic compositions containing them and processes for producing analgesic with them
CA1101860A (fr)	1981-05-26	Traduction non-disponible
US4340737A (en)	1982-07-20	9-Hydroxyoctahydrobenzo[C]quinolines and intermediates therefor
US4118559A (en)	1978-10-03	9-Hydroxyhexahydrodibenzo[O,d]pyrans, 1-substituted-9-hydroxyhexahydrodibenzo[b,d]pyrans and intermediates therefor
IE55991B1 (en)	1991-03-13	Bicyclic benzo fused compounds
NO803693L (no)	1981-06-09	2,3-indoldion-derivater.
US4351833A (en)	1982-09-28	9-Amino-1-hydroxyoctahydrobenzo[c]quinolines and derivatives thereof as analgesics and anti-emetics
HU180916B (hu)	1983-05-30	Eljárás benzo[c]kinolin-származékok előállítására
US4285867A (en)	1981-08-25	Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor
Engelhardt et al.	1968	Antidepressants. Tetrabenazine-antagonizing activity in a series of 5H-dibenzo [cycloheptene-5-propylamines
US4400385A (en)	1983-08-23	9-Hydroxyoctahydrobenzo [c]quinolines, analgesic compositions containing them and processes for producing analgesia with them
US4380542A (en)	1983-04-19	9-Hydroxyoctahydrobenzo[c]quinolines and their pharmaceutical compositions and method of use
US4486609A (en)	1984-12-04	Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor
KR820001355B1 (ko)	1982-07-29	벤조〔c] 퀴놀린의 제조방법
US4835192A (en)	1989-05-30	Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor
KR820001354B1 (ko)	1982-07-29	벤조[c]퀴놀린의 제조방법
US4933475A (en)	1990-06-12	Pharmacologically active 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor
US4331602A (en)	1982-05-25	Pharmacologically active 4-[2-hydroxy-4-(substituted]phenyl)naphthalen-2(1H)-ones and 2-ols, derivatives thereof and intermediates therefor