NO324505B1 - Azetidinderivater, deres fremstilling og farmasoytiske preparat inneholdende forbindelsene - Google Patents
Azetidinderivater, deres fremstilling og farmasoytiske preparat inneholdende forbindelsene Download PDFInfo
- Publication number
- NO324505B1 NO324505B1 NO20024175A NO20024175A NO324505B1 NO 324505 B1 NO324505 B1 NO 324505B1 NO 20024175 A NO20024175 A NO 20024175A NO 20024175 A NO20024175 A NO 20024175A NO 324505 B1 NO324505 B1 NO 324505B1
- Authority
- NO
- Norway
- Prior art keywords
- residue
- methyl
- formula
- chlorophenyl
- hydrogen atom
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 167
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical class C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 title claims description 56
- 238000002360 preparation method Methods 0.000 title claims description 47
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 313
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 188
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 157
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 116
- 238000000034 method Methods 0.000 claims description 109
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- -1 -COOalk Chemical group 0.000 claims description 100
- 229910052786 argon Inorganic materials 0.000 claims description 90
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 84
- 150000003839 salts Chemical class 0.000 claims description 65
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 58
- 239000011707 mineral Substances 0.000 claims description 58
- 150000007524 organic acids Chemical class 0.000 claims description 52
- 150000007522 mineralic acids Chemical class 0.000 claims description 50
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 33
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 27
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 230000003287 optical effect Effects 0.000 claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 150000004820 halides Chemical class 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 229910052701 rubidium Inorganic materials 0.000 claims description 6
- WHHOALSBZGOHKD-UHFFFAOYSA-N 1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)-methylsulfonylmethyl]azetidine Chemical compound C=1C(F)=CC(F)=CC=1C(S(=O)(=O)C)C(C1)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 WHHOALSBZGOHKD-UHFFFAOYSA-N 0.000 claims description 5
- CCOOAROJUCENFX-UHFFFAOYSA-N 2-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]-2-(3,5-difluorophenyl)-n-propan-2-ylacetamide Chemical compound C=1C(F)=CC(F)=CC=1C(C(=O)NC(C)C)C(C1)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 CCOOAROJUCENFX-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- ACXVVMBUFIJKPS-UHFFFAOYSA-N 1-[bis(4-chlorophenyl)methyl]-3-[1-(3,5-difluorophenyl)-1-methylsulfonylethyl]azetidine Chemical compound C=1C(F)=CC(F)=CC=1C(S(C)(=O)=O)(C)C(C1)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 ACXVVMBUFIJKPS-UHFFFAOYSA-N 0.000 claims description 4
- RPVLFZFAWKBHSZ-UHFFFAOYSA-N 5-[(4-chlorophenyl)-[3-[(3,5-difluorophenyl)-methylsulfonylmethyl]azetidin-1-yl]methyl]pyrimidine Chemical compound C=1C(F)=CC(F)=CC=1C(S(=O)(=O)C)C(C1)CN1C(C=1C=NC=NC=1)C1=CC=C(Cl)C=C1 RPVLFZFAWKBHSZ-UHFFFAOYSA-N 0.000 claims description 4
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 150000001350 alkyl halides Chemical class 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 150000001336 alkenes Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- CCOOAROJUCENFX-VWLOTQADSA-N (2r)-2-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]-2-(3,5-difluorophenyl)-n-propan-2-ylacetamide Chemical compound C1C([C@@H](C(=O)NC(C)C)C=2C=C(F)C=C(F)C=2)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 CCOOAROJUCENFX-VWLOTQADSA-N 0.000 claims description 2
- TYCYYNMXAWMHEA-AREMUKBSSA-N (2s)-2-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]-2-(3,5-difluorophenyl)-n-(2-methylpropyl)acetamide Chemical compound C1C([C@H](C(=O)NCC(C)C)C=2C=C(F)C=C(F)C=2)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 TYCYYNMXAWMHEA-AREMUKBSSA-N 0.000 claims description 2
- HVPPNCDSPWPNCQ-MUUNZHRXSA-N (2s)-2-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]-n-cyclohexyl-2-(3,5-difluorophenyl)acetamide Chemical compound FC1=CC(F)=CC([C@H](C2CN(C2)C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(=O)NC2CCCCC2)=C1 HVPPNCDSPWPNCQ-MUUNZHRXSA-N 0.000 claims description 2
- ACXVVMBUFIJKPS-RUZDIDTESA-N 1-[bis(4-chlorophenyl)methyl]-3-[(1s)-1-(3,5-difluorophenyl)-1-methylsulfonylethyl]azetidine Chemical compound C1C([C@@](C)(C=2C=C(F)C=C(F)C=2)S(C)(=O)=O)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 ACXVVMBUFIJKPS-RUZDIDTESA-N 0.000 claims description 2
- TYCYYNMXAWMHEA-UHFFFAOYSA-N 2-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]-2-(3,5-difluorophenyl)-n-(2-methylpropyl)acetamide Chemical compound C=1C(F)=CC(F)=CC=1C(C(=O)NCC(C)C)C(C1)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 TYCYYNMXAWMHEA-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 150000002390 heteroarenes Chemical class 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 11
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- ACXVVMBUFIJKPS-VWLOTQADSA-N 1-[bis(4-chlorophenyl)methyl]-3-[(1r)-1-(3,5-difluorophenyl)-1-methylsulfonylethyl]azetidine Chemical compound C1C([C@](C)(C=2C=C(F)C=C(F)C=2)S(C)(=O)=O)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 ACXVVMBUFIJKPS-VWLOTQADSA-N 0.000 claims 1
- LSFVAWPBOKTUNC-XMMPIXPASA-N 1-[bis(4-chlorophenyl)methyl]-3-[(r)-(3,5-difluorophenyl)-methylsulfonylmethyl]-3-methylazetidine Chemical compound C1C(C)([C@@H](C=2C=C(F)C=C(F)C=2)S(C)(=O)=O)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 LSFVAWPBOKTUNC-XMMPIXPASA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- ZQNYHTGXEOWXHC-HSZRJFAPSA-N ClC1=CC=C(C=C1)C(N1CC(C1)[C@H](S(=O)(=O)C)C=1C=NC=CC=1)C1=CC=C(C=C1)Cl Chemical compound ClC1=CC=C(C=C1)C(N1CC(C1)[C@H](S(=O)(=O)C)C=1C=NC=CC=1)C1=CC=C(C=C1)Cl ZQNYHTGXEOWXHC-HSZRJFAPSA-N 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 125000005936 piperidyl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 729
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 315
- 239000000243 solution Substances 0.000 description 269
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 202
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 202
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 187
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 170
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 157
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 138
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 132
- 239000000203 mixture Substances 0.000 description 111
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 109
- 238000003756 stirring Methods 0.000 description 105
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 97
- 239000007787 solid Substances 0.000 description 88
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 80
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 78
- 235000019341 magnesium sulphate Nutrition 0.000 description 78
- 238000005160 1H NMR spectroscopy Methods 0.000 description 77
- 239000011541 reaction mixture Substances 0.000 description 76
- 239000012429 reaction media Substances 0.000 description 74
- 238000001033 granulometry Methods 0.000 description 73
- 239000000741 silica gel Substances 0.000 description 73
- 229910002027 silica gel Inorganic materials 0.000 description 73
- 239000012074 organic phase Substances 0.000 description 64
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 59
- 239000000377 silicon dioxide Substances 0.000 description 58
- 238000006243 chemical reaction Methods 0.000 description 56
- 239000012442 inert solvent Substances 0.000 description 55
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 50
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 43
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 39
- 238000009835 boiling Methods 0.000 description 39
- 239000002904 solvent Substances 0.000 description 39
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 239000013078 crystal Substances 0.000 description 38
- 239000000725 suspension Substances 0.000 description 37
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 36
- 239000000047 product Substances 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000000843 powder Substances 0.000 description 33
- 239000003921 oil Substances 0.000 description 32
- 235000019198 oils Nutrition 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
- 229920006395 saturated elastomer Polymers 0.000 description 28
- 239000012279 sodium borohydride Substances 0.000 description 28
- 229910000033 sodium borohydride Inorganic materials 0.000 description 28
- 238000010828 elution Methods 0.000 description 27
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 239000011521 glass Substances 0.000 description 25
- 238000004587 chromatography analysis Methods 0.000 description 24
- 230000001143 conditioned effect Effects 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 239000002585 base Substances 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- 239000012043 crude product Substances 0.000 description 21
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 21
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
- 238000011084 recovery Methods 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 125000001931 aliphatic group Chemical group 0.000 description 15
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- JOZMNURWDKIFRO-UHFFFAOYSA-N 2-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]-2-(3,5-difluorophenyl)acetic acid Chemical compound C=1C(F)=CC(F)=CC=1C(C(=O)O)C(C1)CN1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 JOZMNURWDKIFRO-UHFFFAOYSA-N 0.000 description 13
- XPRVSYXHPUYSGF-UHFFFAOYSA-N azetidin-3-one Chemical compound O=C1CNC1 XPRVSYXHPUYSGF-UHFFFAOYSA-N 0.000 description 13
- 239000012153 distilled water Substances 0.000 description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 13
- 235000010755 mineral Nutrition 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- DYGCNLVHBDOEOE-UHFFFAOYSA-N 1,3-difluoro-5-(methylsulfonylmethyl)benzene Chemical compound CS(=O)(=O)CC1=CC(F)=CC(F)=C1 DYGCNLVHBDOEOE-UHFFFAOYSA-N 0.000 description 12
- ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 12
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 235000012239 silicon dioxide Nutrition 0.000 description 12
- 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 11
- 230000008018 melting Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 238000012746 preparative thin layer chromatography Methods 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
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- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 7
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- RZCWTLQDWWLRLL-UHFFFAOYSA-N methyl 4-(4-chlorobenzoyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(=O)C1=CC=C(Cl)C=C1 RZCWTLQDWWLRLL-UHFFFAOYSA-N 0.000 description 3
- LAMSBXJFCQEXRV-UHFFFAOYSA-N methyl 4-[(4-chlorophenyl)-(1,3-dioxoisoindol-2-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(C=1C=CC(Cl)=CC=1)N1C(=O)C2=CC=CC=C2C1=O LAMSBXJFCQEXRV-UHFFFAOYSA-N 0.000 description 3
- HTBWXKXELTZJFR-UHFFFAOYSA-N methyl 4-[(4-chlorophenyl)-hydroxymethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(O)C1=CC=C(Cl)C=C1 HTBWXKXELTZJFR-UHFFFAOYSA-N 0.000 description 3
- XIEPBXPROMTTCT-UHFFFAOYSA-N methyl 4-[amino-(4-chlorophenyl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(N)C1=CC=C(Cl)C=C1 XIEPBXPROMTTCT-UHFFFAOYSA-N 0.000 description 3
- SWRBDIRCOXLCDT-UHFFFAOYSA-N methyl 4-[bromo-(4-chlorophenyl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(Br)C1=CC=C(Cl)C=C1 SWRBDIRCOXLCDT-UHFFFAOYSA-N 0.000 description 3
- QNRQDDOHWYIQLH-UHFFFAOYSA-N methyl 5-(methylsulfonylmethyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(CS(C)(=O)=O)S1 QNRQDDOHWYIQLH-UHFFFAOYSA-N 0.000 description 3
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
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- 150000003463 sulfur Chemical class 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
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- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
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- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0002775A FR2805818B1 (fr) | 2000-03-03 | 2000-03-03 | Derives d'azetidine, leur preparation et les compositions pharmaceutiques les contenant |
| PCT/FR2001/000600 WO2001064632A1 (fr) | 2000-03-03 | 2001-03-01 | Derives d'azetidine, leur preparation et les compositions pharmaceutiques les contenant |
Publications (3)
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|---|---|
| NO20024175D0 NO20024175D0 (no) | 2002-09-02 |
| NO20024175L NO20024175L (no) | 2002-10-29 |
| NO324505B1 true NO324505B1 (no) | 2007-11-05 |
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| NO20024175A NO324505B1 (no) | 2000-03-03 | 2002-09-02 | Azetidinderivater, deres fremstilling og farmasoytiske preparat inneholdende forbindelsene |
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- 2000-03-03 FR FR0002775A patent/FR2805818B1/fr not_active Expired - Fee Related
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2001
- 2001-01-03 UA UA2002097699A patent/UA72593C2/uk unknown
- 2001-02-23 TW TW090104206A patent/TWI230153B/zh not_active IP Right Cessation
- 2001-03-01 BR BR0108871-8A patent/BR0108871A/pt not_active Application Discontinuation
- 2001-03-01 HU HU0301404A patent/HUP0301404A3/hu unknown
- 2001-03-01 CZ CZ20022931A patent/CZ20022931A3/cs unknown
- 2001-03-01 SK SK1245-2002A patent/SK12452002A3/sk unknown
- 2001-03-01 DZ DZ013313A patent/DZ3313A1/fr active
- 2001-03-01 KR KR1020027011515A patent/KR100786411B1/ko not_active Expired - Fee Related
- 2001-03-01 MX MXPA02008360A patent/MXPA02008360A/es active IP Right Grant
- 2001-03-01 EP EP01909937A patent/EP1263720B1/fr not_active Expired - Lifetime
- 2001-03-01 AT AT01909937T patent/ATE432919T1/de active
- 2001-03-01 EE EEP200200487A patent/EE05104B1/et not_active IP Right Cessation
- 2001-03-01 WO PCT/FR2001/000600 patent/WO2001064632A1/fr not_active Ceased
- 2001-03-01 RS YUP-658/02A patent/RS50417B/sr unknown
- 2001-03-01 EA EA200200940A patent/EA006583B1/ru not_active IP Right Cessation
- 2001-03-01 DE DE60138872T patent/DE60138872D1/de not_active Expired - Lifetime
- 2001-03-01 JP JP2001563475A patent/JP2003525268A/ja active Pending
- 2001-03-01 PT PT01909937T patent/PT1263720E/pt unknown
- 2001-03-01 AU AU2001237525A patent/AU2001237525B2/en not_active Ceased
- 2001-03-01 ME MEP-246/08A patent/MEP24608A/xx unknown
- 2001-03-01 NZ NZ521075A patent/NZ521075A/en unknown
- 2001-03-01 OA OA1200200268A patent/OA12220A/fr unknown
- 2001-03-01 SI SI200130936T patent/SI1263720T1/sl unknown
- 2001-03-01 IL IL15142801A patent/IL151428A0/xx unknown
- 2001-03-01 PL PL01357534A patent/PL357534A1/xx not_active Application Discontinuation
- 2001-03-01 AU AU3752501A patent/AU3752501A/xx active Pending
- 2001-03-01 HR HR20020711A patent/HRP20020711A2/hr not_active Application Discontinuation
- 2001-03-01 DK DK01909937T patent/DK1263720T3/da active
- 2001-03-01 CN CNB018081819A patent/CN1185213C/zh not_active Expired - Fee Related
- 2001-03-01 CA CA002400116A patent/CA2400116A1/fr not_active Abandoned
- 2001-03-01 ES ES01909937T patent/ES2328104T3/es not_active Expired - Lifetime
- 2001-03-02 AR ARP010101023A patent/AR027608A1/es active IP Right Grant
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2002
- 2002-08-16 MA MA26781A patent/MA26877A1/fr unknown
- 2002-08-22 IL IL151428A patent/IL151428A/en not_active IP Right Cessation
- 2002-08-28 ZA ZA200206905A patent/ZA200206905B/xx unknown
- 2002-09-02 NO NO20024175A patent/NO324505B1/no not_active IP Right Cessation
- 2002-09-03 BG BG107056A patent/BG107056A/bg unknown
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2009
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