IE42383B1 - 3-fluorbenzodiazepines and processes for their preparation - Google Patents
3-fluorbenzodiazepines and processes for their preparationInfo
- Publication number
- IE42383B1 IE42383B1 IE2767/75A IE276775A IE42383B1 IE 42383 B1 IE42383 B1 IE 42383B1 IE 2767/75 A IE2767/75 A IE 2767/75A IE 276775 A IE276775 A IE 276775A IE 42383 B1 IE42383 B1 IE 42383B1
- Authority
- IE
- Ireland
- Prior art keywords
- fluoro
- dihydro
- benzodiazepin
- compound
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 30
- 230000008569 process Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- PZOZHMBWLDUJCP-UHFFFAOYSA-N 3-fluoro-1H-1,2-benzodiazepine Chemical class FC1=NNC2=C(C=C1)C=CC=C2 PZOZHMBWLDUJCP-UHFFFAOYSA-N 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- -1 α - iodo - N - methyl -acetamido Chemical group 0.000 claims abstract description 45
- 239000002253 acid Substances 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 14
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 125000005059 halophenyl group Chemical group 0.000 claims abstract description 5
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 5
- 230000002140 halogenating effect Effects 0.000 claims abstract description 4
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 4
- 150000001450 anions Chemical class 0.000 claims abstract description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 3
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 3
- 230000001590 oxidative effect Effects 0.000 claims abstract description 3
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- JWGBSFCQLZTKGI-UHFFFAOYSA-N 3-fluoro-7-nitro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1 JWGBSFCQLZTKGI-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- GIBKFDFZIZIKGJ-UHFFFAOYSA-N 7-bromo-1-methyl-5-pyridin-2-yl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(C)C2=CC=C(Br)C=C2C=1C1=CC=CC=N1 GIBKFDFZIZIKGJ-UHFFFAOYSA-N 0.000 claims 1
- NLITWAKTIQNHEQ-UHFFFAOYSA-N 7-chloro-3-fluoro-5-phenyl-1-(2,2,2-trifluoroethyl)-3h-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2N(CC(F)(F)F)C(=O)C(F)N=C1C1=CC=CC=C1 NLITWAKTIQNHEQ-UHFFFAOYSA-N 0.000 claims 1
- KOMKSSWORSXLBP-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-3-fluoro-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1Cl KOMKSSWORSXLBP-UHFFFAOYSA-N 0.000 claims 1
- 150000001204 N-oxides Chemical class 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 43
- 229960003529 diazepam Drugs 0.000 abstract description 32
- 238000006243 chemical reaction Methods 0.000 abstract description 30
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 15
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 abstract description 11
- 238000003682 fluorination reaction Methods 0.000 abstract description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 6
- 150000002148 esters Chemical class 0.000 abstract description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 abstract description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 abstract description 3
- TTZPGQCLBMXJNJ-UHFFFAOYSA-N 3-fluoro-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC=CC=C2NC(=O)C(F)N=C1C1=CC=CC=C1 TTZPGQCLBMXJNJ-UHFFFAOYSA-N 0.000 abstract description 3
- ZBHDTYQJAQDBIH-UHFFFAOYSA-N fluoroacetyl chloride Chemical compound FCC(Cl)=O ZBHDTYQJAQDBIH-UHFFFAOYSA-N 0.000 abstract description 3
- 230000000802 nitrating effect Effects 0.000 abstract description 3
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- 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 abstract description 3
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 abstract description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 abstract description 2
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 230000002082 anti-convulsion Effects 0.000 abstract description 2
- 230000000949 anxiolytic effect Effects 0.000 abstract description 2
- 210000003169 central nervous system Anatomy 0.000 abstract description 2
- 239000003874 central nervous system depressant Substances 0.000 abstract description 2
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 abstract description 2
- 239000011734 sodium Substances 0.000 abstract description 2
- 238000007070 tosylation reaction Methods 0.000 abstract description 2
- 229910004013 NO 2 Inorganic materials 0.000 abstract 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 abstract 2
- QHXFOQLXPHIFPZ-UHFFFAOYSA-N (7-chloro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl) carbonofluoridate Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(OC(=O)F)N=C1C1=CC=CC=C1 QHXFOQLXPHIFPZ-UHFFFAOYSA-N 0.000 abstract 1
- ZTTDAMYXBZJFPC-UHFFFAOYSA-N 1-methyl-1,4-benzodiazepine-2,5-dione Chemical compound O=C1N=CC(=O)N(C)C2=CC=CC=C21 ZTTDAMYXBZJFPC-UHFFFAOYSA-N 0.000 abstract 1
- IHSNVHKPCNBSPW-UHFFFAOYSA-N 2-amino-n-(2-benzoyl-4-chlorophenyl)-2-fluoroacetamide Chemical compound NC(F)C(=O)NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 IHSNVHKPCNBSPW-UHFFFAOYSA-N 0.000 abstract 1
- YXJXSSIMMNJSTH-UHFFFAOYSA-N 2-azido-n-(2-benzoyl-4-chlorophenyl)-2-fluoro-n-methylacetamide Chemical compound [N-]=[N+]=NC(F)C(=O)N(C)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 YXJXSSIMMNJSTH-UHFFFAOYSA-N 0.000 abstract 1
- ZYDRBRFYSFHZKH-UHFFFAOYSA-N 2-bromo-2-fluoroacetyl bromide 2-chloro-2-fluoroacetyl chloride Chemical compound ClC(C(=O)Cl)F.BrC(C(=O)Br)F ZYDRBRFYSFHZKH-UHFFFAOYSA-N 0.000 abstract 1
- VZKOTFAULYVILI-UHFFFAOYSA-N 2-bromo-2-fluoroacetyl chloride Chemical compound FC(Br)C(Cl)=O VZKOTFAULYVILI-UHFFFAOYSA-N 0.000 abstract 1
- MOEOWSMHYGOHDP-UHFFFAOYSA-N 5,7-dichloro-3-fluoro-1-methyl-3h-1,4-benzodiazepin-2-one Chemical compound ClC1=NC(F)C(=O)N(C)C2=CC=C(Cl)C=C21 MOEOWSMHYGOHDP-UHFFFAOYSA-N 0.000 abstract 1
- SCTARSBTRQNRBA-UHFFFAOYSA-N 7-chloro-3-fluoro-4-hydroxy-1-methyl-5-phenyl-3,5-dihydro-1,4-benzodiazepin-2-one Chemical compound ON1C(F)C(=O)N(C)C2=CC=C(Cl)C=C2C1C1=CC=CC=C1 SCTARSBTRQNRBA-UHFFFAOYSA-N 0.000 abstract 1
- SNTJLTUXONRNLX-UHFFFAOYSA-N 7-chloro-3-fluoro-5-phenyl-2,3-dihydro-1h-1,4-benzodiazepin-2-ol Chemical compound N=1C(F)C(O)NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SNTJLTUXONRNLX-UHFFFAOYSA-N 0.000 abstract 1
- DFJHTUVCZCFKJK-UHFFFAOYSA-N 7-chloro-5-(2-chlorophenyl)-3-fluoro-2-oxo-1h-1,4-benzodiazepine-3-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)O)(F)N=C1C1=CC=CC=C1Cl DFJHTUVCZCFKJK-UHFFFAOYSA-N 0.000 abstract 1
- VXLGORQDPJNOAX-UHFFFAOYSA-N C(C)OC(C(F)N=C(C1=C(C=CC(=C1)Cl)N)C1=CC=CC=C1)OCC Chemical compound C(C)OC(C(F)N=C(C1=C(C=CC(=C1)Cl)N)C1=CC=CC=C1)OCC VXLGORQDPJNOAX-UHFFFAOYSA-N 0.000 abstract 1
- KVRZDGZUOUUQIP-UHFFFAOYSA-N ethyl 2-[[(2-amino-5-nitrophenyl)-phenylmethylidene]amino]-2-fluoroacetate Chemical compound C=1C([N+]([O-])=O)=CC=C(N)C=1C(=NC(F)C(=O)OCC)C1=CC=CC=C1 KVRZDGZUOUUQIP-UHFFFAOYSA-N 0.000 abstract 1
- YTJWJBBRIABVPC-UHFFFAOYSA-N ethyl n-(2-benzoyl-4-nitrophenyl)-2-bromo-2-fluoroethanimidate Chemical compound CCOC(C(F)Br)=NC1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1 YTJWJBBRIABVPC-UHFFFAOYSA-N 0.000 abstract 1
- 239000003158 myorelaxant agent Substances 0.000 abstract 1
- XDBQTIRXZGOAEU-UHFFFAOYSA-N n-(2-benzoyl-4-chlorophenyl)-2-(1,3-dioxoisoindol-2-yl)-2-fluoroacetamide Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(F)C(=O)NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 XDBQTIRXZGOAEU-UHFFFAOYSA-N 0.000 abstract 1
- AGQQCYRYWJJNMT-UHFFFAOYSA-N n-(2-benzoyl-4-chlorophenyl)-2-bromo-2-fluoro-n-methylacetamide Chemical compound FC(Br)C(=O)N(C)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 AGQQCYRYWJJNMT-UHFFFAOYSA-N 0.000 abstract 1
- CIMMBUKJPRGPHD-UHFFFAOYSA-N n-[4-chloro-2-(n-hydroxy-c-phenylcarbonimidoyl)phenyl]-2-fluoro-n-methylacetamide Chemical compound FCC(=O)N(C)C1=CC=C(Cl)C=C1C(=NO)C1=CC=CC=C1 CIMMBUKJPRGPHD-UHFFFAOYSA-N 0.000 abstract 1
- YNIJQPGDFIWEPT-UHFFFAOYSA-N n-[4-chloro-2-[(hydroxyamino)-phenylmethyl]phenyl]-2-fluoro-2-iodo-n-methylacetamide Chemical compound FC(I)C(=O)N(C)C1=CC=C(Cl)C=C1C(NO)C1=CC=CC=C1 YNIJQPGDFIWEPT-UHFFFAOYSA-N 0.000 abstract 1
- MWSXNVQQPNIIEQ-UHFFFAOYSA-N n-[[5-chloro-2-(methylamino)phenyl]-phenylmethylidene]hydroxylamine Chemical compound CNC1=CC=C(Cl)C=C1C(=NO)C1=CC=CC=C1 MWSXNVQQPNIIEQ-UHFFFAOYSA-N 0.000 abstract 1
- 238000006798 ring closing metathesis reaction Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 86
- 239000000243 solution Substances 0.000 description 65
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 238000003756 stirring Methods 0.000 description 30
- 230000000875 corresponding effect Effects 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- RGGLEJFUEMKQSH-UHFFFAOYSA-N 1,4-benzodiazepin-2-one Chemical compound O=C1C=NC=C2C=CC=CC2=N1 RGGLEJFUEMKQSH-UHFFFAOYSA-N 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- 238000000354 decomposition reaction Methods 0.000 description 15
- 125000001153 fluoro group Chemical group F* 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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- 239000007858 starting material Substances 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
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- 150000001408 amides Chemical class 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 6
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- 239000012442 inert solvent Substances 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- 239000011698 potassium fluoride Substances 0.000 description 6
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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- 239000002841 Lewis acid Substances 0.000 description 4
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
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- 150000008282 halocarbons Chemical class 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
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- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
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- 241000700159 Rattus Species 0.000 description 3
- WPNMLCMTDCANOZ-UHFFFAOYSA-N [5-chloro-2-(methylamino)phenyl]-phenylmethanone Chemical compound CNC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 WPNMLCMTDCANOZ-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
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- 239000011777 magnesium Substances 0.000 description 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 229910044991 metal oxide Inorganic materials 0.000 description 1
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- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical class [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
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- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 101150009274 nhr-1 gene Proteins 0.000 description 1
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- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000005246 nonafluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
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- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
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- 150000003016 phosphoric acids Chemical class 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
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- 239000012286 potassium permanganate Substances 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
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- 230000001105 regulatory effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
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- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
- 229940096017 silver fluoride Drugs 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
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- 229960002317 succinimide Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960003188 temazepam Drugs 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000007514 turning Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19742460360 DE2460360A1 (de) | 1974-12-20 | 1974-12-20 | 3-fluorbenzodiazepine und verfahren zu ihrer herstellung |
| DE19752542251 DE2542251A1 (de) | 1975-09-23 | 1975-09-23 | 3-fluorbenzodiazepine und verfahren zu ihrer herstellung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE42383L IE42383L (en) | 1976-06-20 |
| IE42383B1 true IE42383B1 (en) | 1980-07-30 |
Family
ID=25768130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2767/75A IE42383B1 (en) | 1974-12-20 | 1975-12-19 | 3-fluorbenzodiazepines and processes for their preparation |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4232016A (en, 2012) |
| JP (1) | JPS5188985A (en, 2012) |
| AT (1) | AT353794B (en, 2012) |
| AU (1) | AU8760075A (en, 2012) |
| CA (1) | CA1100960A (en, 2012) |
| CH (3) | CH617193A5 (en, 2012) |
| CS (1) | CS188984B2 (en, 2012) |
| DD (1) | DD122382A5 (en, 2012) |
| DK (1) | DK583775A (en, 2012) |
| ES (1) | ES443692A1 (en, 2012) |
| FR (1) | FR2294708A1 (en, 2012) |
| GB (1) | GB1480559A (en, 2012) |
| IE (1) | IE42383B1 (en, 2012) |
| IL (1) | IL48665A (en, 2012) |
| IT (1) | IT7948446A0 (en, 2012) |
| LU (1) | LU74049A1 (en, 2012) |
| NL (1) | NL7514861A (en, 2012) |
| SE (1) | SE7514344L (en, 2012) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6032775A (ja) * | 1983-07-30 | 1985-02-19 | Daikin Ind Ltd | 含フッ素ベンゾジアゼピン類 |
| US4479901A (en) * | 1983-08-15 | 1984-10-30 | E. I. Du Pont De Nemours And Company | Fluorination of carbanions with N-fluoro-N-alkylsulfonamides |
| US4690934A (en) * | 1985-09-25 | 1987-09-01 | Nippon Kayaku Kabushiki Kaisha | N-phenylsulfonylisonicotinamide derivatives and their use as fungicides or bactericides |
| US5030632A (en) * | 1986-09-23 | 1991-07-09 | Sandoz Pharm. Corp. | Low dose temazepam |
| US5211954A (en) * | 1986-09-23 | 1993-05-18 | Sandoz Ltd. | Low dose temazepam |
| US5629310A (en) * | 1986-09-23 | 1997-05-13 | Sterling; William R. | Low dose temazepam |
| FR2620449B1 (fr) * | 1987-09-16 | 1991-04-19 | Sanofi Sa | Procede de preparation de derives de benzodiazepine-1,4 one-2 |
| US20090068325A1 (en) * | 2007-09-10 | 2009-03-12 | Gil Depicciotto | Method of treatment of fresh produce |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3121076A (en) * | 1964-02-11 | Benzodiazepinones and processes | ||
| US3371085A (en) * | 1959-12-10 | 1968-02-27 | Hoffmann La Roche | 5-aryl-3h-1,4-benzodiazepin-2(1h)-ones |
| US3296251A (en) * | 1963-02-26 | 1967-01-03 | American Home Prod | 3-mercapto and 3-substituted mercapto-1, 3-dihydro-2h-1, 4-benzodiazepin-2-ones |
| NL298071A (en, 2012) * | 1963-06-04 | |||
| GB1052144A (en, 2012) * | 1964-02-11 | |||
| US3429874A (en) * | 1966-12-22 | 1969-02-25 | Schering Corp | 1-polyhalogenoalkyl-2-oxo-1,3-dihydro-2h-1,4-benzodiazepines |
-
1975
- 1975-12-09 US US05/639,163 patent/US4232016A/en not_active Expired - Lifetime
- 1975-12-11 FR FR7537935A patent/FR2294708A1/fr active Granted
- 1975-12-14 IL IL48665A patent/IL48665A/xx unknown
- 1975-12-16 AU AU87600/75A patent/AU8760075A/en not_active Expired
- 1975-12-17 CS CS758626A patent/CS188984B2/cs unknown
- 1975-12-18 GB GB51893/75A patent/GB1480559A/en not_active Expired
- 1975-12-18 SE SE7514344A patent/SE7514344L/xx unknown
- 1975-12-18 CA CA242,041A patent/CA1100960A/en not_active Expired
- 1975-12-18 LU LU74049A patent/LU74049A1/xx unknown
- 1975-12-18 DD DD190285A patent/DD122382A5/xx unknown
- 1975-12-19 JP JP50152699A patent/JPS5188985A/ja active Pending
- 1975-12-19 ES ES443692A patent/ES443692A1/es not_active Expired
- 1975-12-19 AT AT968875A patent/AT353794B/de not_active IP Right Cessation
- 1975-12-19 NL NL7514861A patent/NL7514861A/xx not_active Application Discontinuation
- 1975-12-19 CH CH1654475A patent/CH617193A5/de not_active IP Right Cessation
- 1975-12-19 DK DK583775A patent/DK583775A/da unknown
- 1975-12-19 IE IE2767/75A patent/IE42383B1/en unknown
-
1979
- 1979-03-22 IT IT7948446A patent/IT7948446A0/it unknown
- 1979-10-16 CH CH930679A patent/CH620685A5/de not_active IP Right Cessation
- 1979-10-16 CH CH930579A patent/CH618433A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH617193A5 (en, 2012) | 1980-05-14 |
| FR2294708A1 (fr) | 1976-07-16 |
| IL48665A0 (en) | 1976-02-29 |
| SE7514344L (sv) | 1976-06-21 |
| DD122382A5 (en, 2012) | 1976-10-05 |
| FR2294708B1 (en, 2012) | 1979-09-21 |
| ATA968875A (de) | 1979-05-15 |
| IT7948446A0 (it) | 1979-03-22 |
| US4232016A (en) | 1980-11-04 |
| CH620685A5 (en, 2012) | 1980-12-15 |
| NL7514861A (nl) | 1976-06-22 |
| ES443692A1 (es) | 1977-10-01 |
| CA1100960A (en) | 1981-05-12 |
| JPS5188985A (en) | 1976-08-04 |
| CH618433A5 (en, 2012) | 1980-07-31 |
| LU74049A1 (en, 2012) | 1977-07-01 |
| CS188984B2 (en) | 1979-03-30 |
| GB1480559A (en) | 1977-07-20 |
| AT353794B (de) | 1979-12-10 |
| DK583775A (da) | 1976-06-21 |
| AU8760075A (en) | 1977-06-23 |
| IL48665A (en) | 1979-11-30 |
| IE42383L (en) | 1976-06-20 |
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