JP2017505302A - トラゾドンおよびその塩酸塩を製造するための改良法 - Google Patents
トラゾドンおよびその塩酸塩を製造するための改良法 Download PDFInfo
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- JP2017505302A JP2017505302A JP2016547540A JP2016547540A JP2017505302A JP 2017505302 A JP2017505302 A JP 2017505302A JP 2016547540 A JP2016547540 A JP 2016547540A JP 2016547540 A JP2016547540 A JP 2016547540A JP 2017505302 A JP2017505302 A JP 2017505302A
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- Prior art keywords
- compound
- chloride
- trazodone
- hydrochloride
- free base
- Prior art date
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- Pending
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- 238000000034 method Methods 0.000 title claims abstract description 119
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 title claims abstract description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 229960003991 trazodone Drugs 0.000 title claims abstract description 43
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 229960002301 trazodone hydrochloride Drugs 0.000 claims abstract description 36
- OHHDIOKRWWOXMT-UHFFFAOYSA-N trazodone hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 OHHDIOKRWWOXMT-UHFFFAOYSA-N 0.000 claims abstract description 36
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract description 34
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 28
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- 238000001556 precipitation Methods 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 239000012535 impurity Substances 0.000 claims abstract description 15
- 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 claims abstract description 14
- NDQKGEFMUGSRNS-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine Chemical compound C1CN(CCCCl)CCN1C1=CC=CC(Cl)=C1 NDQKGEFMUGSRNS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 144
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 235000019441 ethanol Nutrition 0.000 claims description 33
- 239000002904 solvent Substances 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 28
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 28
- 239000012458 free base Substances 0.000 claims description 27
- 239000003444 phase transfer catalyst Substances 0.000 claims description 20
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 239000003963 antioxidant agent Substances 0.000 claims description 18
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 18
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 18
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 17
- 230000003078 antioxidant effect Effects 0.000 claims description 17
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 10
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 10
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 claims description 10
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 10
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 10
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 10
- 239000000473 propyl gallate Substances 0.000 claims description 9
- 235000010388 propyl gallate Nutrition 0.000 claims description 9
- 229940075579 propyl gallate Drugs 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 8
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 230000002152 alkylating effect Effects 0.000 claims description 8
- 229940035429 isobutyl alcohol Drugs 0.000 claims description 8
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- JYDIJFKNXHPWBJ-FBBRVDCYSA-M (s)-[(2r,4s,5r)-1-benzyl-5-ethenyl-1-azoniabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol;chloride Chemical compound [Cl-].C([C@H]([C@H](C1)C=C)C[C@@H]2[C@@H](O)C3=CC=NC4=CC=C(C=C43)OC)C[N+]21CC1=CC=CC=C1 JYDIJFKNXHPWBJ-FBBRVDCYSA-M 0.000 claims description 4
- QAQSNXHKHKONNS-UHFFFAOYSA-N 1-ethyl-2-hydroxy-4-methyl-6-oxopyridine-3-carboxamide Chemical compound CCN1C(O)=C(C(N)=O)C(C)=CC1=O QAQSNXHKHKONNS-UHFFFAOYSA-N 0.000 claims description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 4
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 claims description 4
- CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 4
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 4
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 4
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- WPPGURUIRLDHAB-UHFFFAOYSA-M triethyl(hexadecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](CC)(CC)CC WPPGURUIRLDHAB-UHFFFAOYSA-M 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 claims description 3
- AQZSPJRLCJSOED-UHFFFAOYSA-M trimethyl(octyl)azanium;chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(C)C AQZSPJRLCJSOED-UHFFFAOYSA-M 0.000 claims description 3
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 125000005909 ethyl alcohol group Chemical group 0.000 claims 1
- YALSYPYLQDHODG-UHFFFAOYSA-L hexadecyl(trimethyl)azanium dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C.CCCCCCCCCCCCCCCC[N+](C)(C)C YALSYPYLQDHODG-UHFFFAOYSA-L 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 239000000047 product Substances 0.000 description 50
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- 239000000706 filtrate Substances 0.000 description 14
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 9
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
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- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 2
- JVLRNANYLVRULL-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine;hydrochloride Chemical compound [Cl-].C1CN(CCCCl)CC[NH+]1C1=CC=CC(Cl)=C1 JVLRNANYLVRULL-UHFFFAOYSA-N 0.000 description 2
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- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- 239000000932 sedative agent Substances 0.000 description 2
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- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
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- XZFRYYHZODSXRL-UHFFFAOYSA-N 2-[3-[bis(2-chloroethyl)amino]propyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one Chemical compound C1=CC=CN2C(=O)N(CCCN(CCCl)CCCl)N=C21 XZFRYYHZODSXRL-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
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- UBLVFJOJWCMQKZ-UHFFFAOYSA-N 3-chloro-n,n-bis(2-chloroethyl)aniline Chemical compound ClCCN(CCCl)C1=CC=CC(Cl)=C1 UBLVFJOJWCMQKZ-UHFFFAOYSA-N 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- UJTTUOLQLCQZEA-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(4-hydroxybutyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCCO)C3=CC=CC=C3C2=C1 UJTTUOLQLCQZEA-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 206010021703 Indifference Diseases 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 231100000024 genotoxic Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- -1 i.e. Chemical compound 0.000 description 1
- 230000008517 inhibition of serotonin uptake Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 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
- 125000000913 palmityl group Chemical group [H]C([*])([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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
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- 230000013275 serotonin uptake Effects 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN203/MUM/2014 | 2014-01-21 | ||
| PCT/IB2014/066841 WO2015110883A1 (en) | 2014-01-21 | 2014-12-12 | An improved process for the preparation of trazodone and hydrochloride salt thereof |
| IN203MU2014 IN2014MU00203A (enrdf_load_stackoverflow) | 2014-01-21 | 2014-12-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2017505302A true JP2017505302A (ja) | 2017-02-16 |
Family
ID=53680891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016547540A Pending JP2017505302A (ja) | 2014-01-21 | 2014-12-12 | トラゾドンおよびその塩酸塩を製造するための改良法 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3097099A4 (enrdf_load_stackoverflow) |
| JP (1) | JP2017505302A (enrdf_load_stackoverflow) |
| CA (1) | CA2937417C (enrdf_load_stackoverflow) |
| IL (1) | IL246835A0 (enrdf_load_stackoverflow) |
| IN (1) | IN2014MU00203A (enrdf_load_stackoverflow) |
| WO (1) | WO2015110883A1 (enrdf_load_stackoverflow) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL234822B1 (pl) | 2017-03-14 | 2020-04-30 | Politechnika Krakowska Im Tadeusza Kosciuszki | Sposób otrzymywania trazodonu |
| CN117517545A (zh) * | 2023-12-08 | 2024-02-06 | 重庆锐恩医药有限公司 | 一种盐酸曲唑酮有关物质检测方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3381009A (en) * | 1965-12-15 | 1968-04-30 | Acraf | Triazole-(4,3-a)-pyridines |
| WO2009105604A1 (en) * | 2008-02-20 | 2009-08-27 | Auspex Pharmaceuticals, Inc. | Substituted triazolopyridines |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4252806A (en) * | 1979-09-24 | 1981-02-24 | Mead Johnson & Company | Triazoloquinolones |
| HU201324B (en) * | 1988-07-29 | 1990-10-28 | Egyt Gyogyszervegyeszeti Gyar | New process for production of substituated 1,2,4-triasole (4,3-a)-piridin-2 (2h)-on |
| ITMI20071603A1 (it) * | 2007-08-03 | 2009-02-04 | Acraf | Trazodone e trazodone cloridrato in forma purificata |
-
2014
- 2014-12-12 IN IN203MU2014 patent/IN2014MU00203A/en unknown
- 2014-12-12 EP EP14879353.2A patent/EP3097099A4/en not_active Ceased
- 2014-12-12 JP JP2016547540A patent/JP2017505302A/ja active Pending
- 2014-12-12 CA CA2937417A patent/CA2937417C/en active Active
- 2014-12-12 WO PCT/IB2014/066841 patent/WO2015110883A1/en active Application Filing
-
2016
- 2016-07-19 IL IL246835A patent/IL246835A0/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3381009A (en) * | 1965-12-15 | 1968-04-30 | Acraf | Triazole-(4,3-a)-pyridines |
| WO2009105604A1 (en) * | 2008-02-20 | 2009-08-27 | Auspex Pharmaceuticals, Inc. | Substituted triazolopyridines |
Non-Patent Citations (3)
| Title |
|---|
| AICHE JOURNAL, vol. 44, no. 3, JPN6018029771, 1998, pages 612 - 646 * |
| JOURNAL OF CHEMICAL AND PHARMACEUTICAL RESEARCH, vol. 2, no. 1, JPN6018029765, 2010, pages 458 - 472 * |
| JOURNAL OF ORGANIC CHEMISTRY, vol. 39, no. 23, JPN6018029767, 1974, pages 3416 - 3418 * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL246835A0 (en) | 2016-08-31 |
| CA2937417A1 (en) | 2015-07-30 |
| EP3097099A1 (en) | 2016-11-30 |
| IN2014MU00203A (enrdf_load_stackoverflow) | 2015-09-25 |
| CA2937417C (en) | 2022-04-12 |
| EP3097099A4 (en) | 2017-08-23 |
| WO2015110883A1 (en) | 2015-07-30 |
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