MD3749668T2 - Procedeu continuu de preparare a trazodonei - Google Patents
Procedeu continuu de preparare a trazodonei Download PDFInfo
- Publication number
- MD3749668T2 MD3749668T2 MDE20201242T MDE20201242T MD3749668T2 MD 3749668 T2 MD3749668 T2 MD 3749668T2 MD E20201242 T MDE20201242 T MD E20201242T MD E20201242 T MDE20201242 T MD E20201242T MD 3749668 T2 MD3749668 T2 MD 3749668T2
- Authority
- MD
- Moldova
- Prior art keywords
- continuous
- reactor
- chlorophenyl
- piperazine
- process according
- Prior art date
Links
- 238000010924 continuous production Methods 0.000 title claims abstract description 123
- 229960003991 trazodone Drugs 0.000 title claims abstract description 73
- 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 73
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 67
- 230000008569 process Effects 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 66
- 150000001875 compounds Chemical class 0.000 claims description 51
- 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 description 46
- 239000007864 aqueous solution Substances 0.000 claims description 43
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- LJRXNXBFJXXRNQ-UHFFFAOYSA-N 2h-[1,2,4]triazolo[4,3-a]pyridin-3-one Chemical compound C1=CC=CN2C(=O)NN=C21 LJRXNXBFJXXRNQ-UHFFFAOYSA-N 0.000 claims description 32
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 claims description 27
- 239000003960 organic solvent Substances 0.000 claims description 25
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 24
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 22
- 239000012074 organic phase Substances 0.000 claims description 22
- 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 description 21
- 229960002301 trazodone hydrochloride Drugs 0.000 claims description 21
- 150000007514 bases Chemical class 0.000 claims description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 18
- 239000008346 aqueous phase Substances 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 11
- 239000011541 reaction mixture Substances 0.000 claims description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 150000007529 inorganic bases Chemical class 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-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
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 4
- 239000000908 ammonium hydroxide Substances 0.000 claims description 4
- 229940035429 isobutyl alcohol Drugs 0.000 claims description 4
- 239000000395 magnesium oxide Substances 0.000 claims description 4
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 4
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003880 polar aprotic solvent Substances 0.000 claims description 4
- 239000011736 potassium bicarbonate Substances 0.000 claims description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 235000011181 potassium carbonates Nutrition 0.000 claims description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 239000001488 sodium phosphate Substances 0.000 claims description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 4
- 235000012245 magnesium oxide Nutrition 0.000 claims description 3
- 238000011084 recovery Methods 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 2
- 150000004982 aromatic amines Chemical class 0.000 claims description 2
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000003586 protic polar solvent Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- 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 1
- 150000001412 amines Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000002585 base Substances 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 6
- 239000004810 polytetrafluoroethylene Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000002152 alkylating effect Effects 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229920000840 ethylene tetrafluoroethylene copolymer Polymers 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 3
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- -1 Compound III Compound Chemical class 0.000 description 2
- 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- QRJJWPOFLQIFOC-UHFFFAOYSA-N 1-chloro-2-phenyl-4-propylpiperazine Chemical compound ClN1C(CN(CC1)CCC)C1=CC=CC=C1 QRJJWPOFLQIFOC-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- WYSGRZOBNVDTRM-UHFFFAOYSA-N C1=CC=NC=C1.O=C1C=NN=N1 Chemical compound C1=CC=NC=C1.O=C1C=NN=N1 WYSGRZOBNVDTRM-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 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 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000000966 norepinephrine reuptake Effects 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J14/00—Chemical processes in general for reacting liquids with liquids; Apparatus specially adapted therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2204/00—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices
- B01J2204/007—Aspects relating to the heat-exchange of the feed or outlet devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00002—Chemical plants
- B01J2219/00027—Process aspects
- B01J2219/00029—Batch processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00002—Chemical plants
- B01J2219/00027—Process aspects
- B01J2219/00033—Continuous processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00788—Three-dimensional assemblies, i.e. the reactor comprising a form other than a stack of plates
- B01J2219/00792—One or more tube-shaped elements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00801—Means to assemble
- B01J2219/0081—Plurality of modules
- B01J2219/00813—Fluidic connections
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00851—Additional features
- B01J2219/00867—Microreactors placed in series, on the same or on different supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00851—Additional features
- B01J2219/00869—Microreactors placed in parallel, on the same or on different supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00851—Additional features
- B01J2219/00871—Modular assembly
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00873—Heat exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
- B01J8/02—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds
- B01J8/0292—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds with stationary packing material in the bed, e.g. bricks, wire rings, baffles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
- B01J8/18—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with fluidised particles
- B01J8/24—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with fluidised particles according to "fluidised-bed" technique
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Combustion & Propulsion (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18155470 | 2018-02-07 | ||
| PCT/EP2019/052690 WO2019154770A1 (en) | 2018-02-07 | 2019-02-05 | Continuous process for the preparation of trazodone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MD3749668T2 true MD3749668T2 (ro) | 2022-08-31 |
Family
ID=61187146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MDE20201242T MD3749668T2 (ro) | 2018-02-07 | 2019-02-05 | Procedeu continuu de preparare a trazodonei |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US12221438B2 (https=) |
| EP (1) | EP3749668B1 (https=) |
| JP (1) | JP7301858B2 (https=) |
| KR (1) | KR102646651B1 (https=) |
| CN (1) | CN111886235B (https=) |
| AU (1) | AU2019217490B2 (https=) |
| BR (1) | BR112020015885A2 (https=) |
| CA (1) | CA3089552A1 (https=) |
| CY (1) | CY1125298T1 (https=) |
| DK (1) | DK3749668T3 (https=) |
| EA (1) | EA202091834A1 (https=) |
| ES (1) | ES2916406T3 (https=) |
| GE (2) | GEAP202215429A (https=) |
| HR (1) | HRP20220733T1 (https=) |
| HU (1) | HUE058990T2 (https=) |
| IL (1) | IL276483B2 (https=) |
| LT (1) | LT3749668T (https=) |
| MD (1) | MD3749668T2 (https=) |
| MX (1) | MX394182B (https=) |
| PL (1) | PL3749668T3 (https=) |
| PT (1) | PT3749668T (https=) |
| RS (1) | RS63323B1 (https=) |
| SG (1) | SG11202006948XA (https=) |
| SI (1) | SI3749668T1 (https=) |
| SM (1) | SMT202200277T1 (https=) |
| UA (1) | UA126870C2 (https=) |
| WO (1) | WO2019154770A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116253696A (zh) * | 2021-12-10 | 2023-06-13 | 安徽省化工研究院 | 一种噁草酮的连续流制备方法 |
| CN114891019B (zh) * | 2022-02-25 | 2024-06-04 | 复旦大学 | 一种乙烯基硫醚化合物的连续流制备方法 |
| CN117358178A (zh) * | 2023-12-08 | 2024-01-09 | 天津凯莱英医药科技发展有限公司 | 丙硫菌唑的连续化合成系统及方法 |
| CN118162064B (zh) * | 2024-05-15 | 2024-08-30 | 济南大学 | 一种美罗培南母核中间体的连续化生产装置及方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1066857B (it) | 1965-12-15 | 1985-03-12 | Acraf | Derivati della s ipiazolo 4.3 a piridina e processi per la loro preparazione |
| US4252806A (en) * | 1979-09-24 | 1981-02-24 | Mead Johnson & Company | Triazoloquinolones |
| US4254124A (en) | 1979-09-24 | 1981-03-03 | Mead Johnson & Company | Antidepressant agent |
| 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 |
| AU663057B2 (en) | 1990-09-28 | 1995-09-28 | Pharmacia & Upjohn Company | Anthelmintic and anticoccidal 3-carbamoyl-4-hydroxycoumarins |
| CA2182241C (en) | 1996-07-29 | 2002-09-17 | Bo Lei | Methods for the manufacture of nefazodone |
| IT1314283B1 (it) | 1999-12-16 | 2002-12-06 | Acraf | Trazodone cloridrato ed un procedimento per prepararlo. |
| ITMI20071603A1 (it) | 2007-08-03 | 2009-02-04 | Acraf | Trazodone e trazodone cloridrato in forma purificata |
| WO2017166050A1 (zh) * | 2016-03-29 | 2017-10-05 | 深圳市泛谷药业股份有限公司 | 一种盐酸曲唑酮的制备方法 |
| CN105777745A (zh) | 2016-03-29 | 2016-07-20 | 深圳市泛谷药业股份有限公司 | 一种盐酸曲唑酮的制备方法 |
-
2019
- 2019-02-05 DK DK19702619.8T patent/DK3749668T3/da active
- 2019-02-05 MX MX2020008241A patent/MX394182B/es unknown
- 2019-02-05 LT LTEPPCT/EP2019/052690T patent/LT3749668T/lt unknown
- 2019-02-05 JP JP2020542436A patent/JP7301858B2/ja active Active
- 2019-02-05 US US16/967,337 patent/US12221438B2/en active Active
- 2019-02-05 BR BR112020015885-2A patent/BR112020015885A2/pt unknown
- 2019-02-05 WO PCT/EP2019/052690 patent/WO2019154770A1/en not_active Ceased
- 2019-02-05 PT PT197026198T patent/PT3749668T/pt unknown
- 2019-02-05 RS RS20220563A patent/RS63323B1/sr unknown
- 2019-02-05 AU AU2019217490A patent/AU2019217490B2/en active Active
- 2019-02-05 EP EP19702619.8A patent/EP3749668B1/en active Active
- 2019-02-05 SM SM20220277T patent/SMT202200277T1/it unknown
- 2019-02-05 KR KR1020207023772A patent/KR102646651B1/ko active Active
- 2019-02-05 IL IL276483A patent/IL276483B2/en unknown
- 2019-02-05 SG SG11202006948XA patent/SG11202006948XA/en unknown
- 2019-02-05 GE GEAP202215429A patent/GEAP202215429A/en unknown
- 2019-02-05 UA UAA202004708A patent/UA126870C2/uk unknown
- 2019-02-05 CA CA3089552A patent/CA3089552A1/en active Pending
- 2019-02-05 ES ES19702619T patent/ES2916406T3/es active Active
- 2019-02-05 HR HRP20220733TT patent/HRP20220733T1/hr unknown
- 2019-02-05 SI SI201930263T patent/SI3749668T1/sl unknown
- 2019-02-05 EA EA202091834A patent/EA202091834A1/ru unknown
- 2019-02-05 CN CN201980011910.0A patent/CN111886235B/zh active Active
- 2019-02-05 GE GEAP201915429A patent/GEP20227417B/en unknown
- 2019-02-05 HU HUE19702619A patent/HUE058990T2/hu unknown
- 2019-02-05 MD MDE20201242T patent/MD3749668T2/ro unknown
- 2019-02-05 PL PL19702619.8T patent/PL3749668T3/pl unknown
-
2022
- 2022-06-23 CY CY20221100435T patent/CY1125298T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MD3749668T2 (ro) | Procedeu continuu de preparare a trazodonei | |
| CN106938976A (zh) | 一种以醇和胺为原料催化氧化制备亚胺类化合物的方法 | |
| CN107522667B (zh) | 地西泮-d8及其制备方法 | |
| CN110922409A (zh) | 制备btk抑制剂泽布替尼的方法 | |
| CN110981816A (zh) | 一种4-氨基-2.6-二甲氧基嘧啶的合成方法 | |
| CN106397334A (zh) | 一种苯并咪唑类驱虫药苯硫咪唑的制备方法 | |
| ITMI20002324A1 (it) | Processo per la preparazione di maleato di fluvossamina | |
| CN110903264B (zh) | 一种制备二氮嗪的方法 | |
| CN103497174A (zh) | 泊利度胺的制备和精制方法 | |
| CN114773348B (zh) | 一种咪达唑仑的制备方法及其中间体 | |
| US9688685B2 (en) | Method for preparing volasertib and intermediate thereof | |
| HK40039271B (en) | Continuous process for the preparation of trazodone | |
| HK40039271A (en) | Continuous process for the preparation of trazodone | |
| EA040792B1 (ru) | Непрерывный способ получения тразодона | |
| CN108101899B (zh) | IDO1抑制剂Epacadostat中间体的制备方法 | |
| HU231283B1 (hu) | Eljárás a flibanserin többlépéses folyamatos áramú előállítására | |
| CN111285823B (zh) | 一种萘并[1,8-de][1,3]噻嗪-2-硫醇的制备方法 | |
| CN116041222A (zh) | 一种咪达唑仑的制备方法及其中间体 | |
| CN119264130A (zh) | 一种阿哌沙班及其中间体的制备方法 | |
| CN106866439A (zh) | 氯甲西泮杂质的制备工艺 | |
| CN104910101A (zh) | 伊马替尼中间体4-(4-甲基哌嗪-1-基甲基)苯甲酸盐酸盐的合成工艺 | |
| CN101362767B (zh) | 一类四氢吡咯二螺环类化合物中间体的制备方法 | |
| CN111153863A (zh) | 一种合成动物用抗球虫药物妥曲珠利的方法 | |
| CN110621652A (zh) | 二氨基苯化合物的制造方法 | |
| CN105566226A (zh) | 盐酸苯达莫司汀二聚体的制备方法与应用 |