CH572484A5 - Substd 4h s-triazolo (43-a)(1 4) benzodiazepins - from 2-(3-halomethy s-triazol-4-yl) benzophenones and ammonia or hexamethylene tetramine - Google Patents
Substd 4h s-triazolo (43-a)(1 4) benzodiazepins - from 2-(3-halomethy s-triazol-4-yl) benzophenones and ammonia or hexamethylene tetramineInfo
- Publication number
- CH572484A5 CH572484A5 CH1480874A CH1480874A CH572484A5 CH 572484 A5 CH572484 A5 CH 572484A5 CH 1480874 A CH1480874 A CH 1480874A CH 1480874 A CH1480874 A CH 1480874A CH 572484 A5 CH572484 A5 CH 572484A5
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- parts
- formula
- mixture
- volume
- Prior art date
Links
- 235000010299 hexamethylene tetramine Nutrition 0.000 title claims abstract description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 title claims description 22
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 title claims description 20
- 239000004312 hexamethylene tetramine Substances 0.000 title claims description 10
- 229910021529 ammonia Inorganic materials 0.000 title claims description 8
- 239000012965 benzophenone Substances 0.000 title abstract description 4
- -1 s-triazol-4-yl Chemical group 0.000 title description 24
- 150000008366 benzophenones Chemical class 0.000 title description 3
- 229960004011 methenamine Drugs 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 41
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 92
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 71
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 235000011054 acetic acid Nutrition 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 19
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 18
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 12
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 10
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 9
- 235000019253 formic acid Nutrition 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 150000004820 halides Chemical class 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 235000019260 propionic acid Nutrition 0.000 claims description 6
- 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 claims description 6
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 5
- 150000008065 acid anhydrides Chemical class 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- 229910001516 alkali metal iodide Inorganic materials 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 229960005215 dichloroacetic acid Drugs 0.000 claims description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims 2
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 229960004365 benzoic acid Drugs 0.000 claims 1
- 229960003424 phenylacetic acid Drugs 0.000 claims 1
- 239000003279 phenylacetic acid Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract description 52
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 abstract description 5
- 229940035363 muscle relaxants Drugs 0.000 abstract description 2
- 239000003158 myorelaxant agent Substances 0.000 abstract description 2
- 229940125681 anticonvulsant agent Drugs 0.000 abstract 1
- 239000001961 anticonvulsive agent Substances 0.000 abstract 1
- 125000005179 haloacetyl group Chemical group 0.000 abstract 1
- 229940125723 sedative agent Drugs 0.000 abstract 1
- 239000000932 sedative agent Substances 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 68
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- 239000013078 crystal Substances 0.000 description 52
- 238000002844 melting Methods 0.000 description 51
- 230000008018 melting Effects 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 238000000921 elemental analysis Methods 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 30
- 238000001953 recrystallisation Methods 0.000 description 28
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 25
- 229960000583 acetic acid Drugs 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 238000003756 stirring Methods 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 239000007858 starting material Substances 0.000 description 14
- 239000010410 layer Substances 0.000 description 13
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- 235000017550 sodium carbonate Nutrition 0.000 description 12
- 238000004821 distillation Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 7
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 7
- ZAXFFQSOWYVGER-UHFFFAOYSA-N 3-amino-6-chloro-4-phenylquinazolin-4-ol Chemical compound NN1C=NC2=CC=C(Cl)C=C2C1(O)C1=CC=CC=C1 ZAXFFQSOWYVGER-UHFFFAOYSA-N 0.000 description 7
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 7
- UZXMWIGOTGGWPU-UHFFFAOYSA-N 3-amino-2-methyl-6-nitro-4-phenylquinazolin-4-ol Chemical compound NN1C(=NC2=CC=C(C=C2C1(C1=CC=CC=C1)O)[N+](=O)[O-])C UZXMWIGOTGGWPU-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- IEQYCNKKNGEMAN-UHFFFAOYSA-N 3-amino-6-chloro-2-methyl-4-phenylquinazolin-4-ol Chemical compound NN1C(C)=NC2=CC=C(Cl)C=C2C1(O)C1=CC=CC=C1 IEQYCNKKNGEMAN-UHFFFAOYSA-N 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 4
- FDIDQVQHCGSJMT-UHFFFAOYSA-N 3-amino-6-nitro-4-phenylquinazolin-4-ol Chemical compound NN1C=NC2=CC=C(C=C2C1(C1=CC=CC=C1)O)[N+](=O)[O-] FDIDQVQHCGSJMT-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- DNMANFUDPSVMBH-UHFFFAOYSA-N [5-chloro-2-[3-(chloromethyl)-1,2,4-triazol-4-yl]phenyl]-phenylmethanone;hydrochloride Chemical compound Cl.ClCC1=NN=CN1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 DNMANFUDPSVMBH-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229940106681 chloroacetic acid Drugs 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 4
- 150000002905 orthoesters Chemical class 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- PZPZDEIASIKHPY-UHFFFAOYSA-N (2-amino-5-nitrophenyl)-phenylmethanone Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1 PZPZDEIASIKHPY-UHFFFAOYSA-N 0.000 description 3
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 3
- VWHPCNYXEBGHQF-UHFFFAOYSA-N 3-amino-2,6-dimethyl-4-phenylquinazolin-4-ol Chemical compound NN1C(C)=NC2=CC=C(C)C=C2C1(O)C1=CC=CC=C1 VWHPCNYXEBGHQF-UHFFFAOYSA-N 0.000 description 3
- AXPOBLRMPCKWIT-UHFFFAOYSA-N 3-amino-4-phenyl-6-(trifluoromethyl)quinazolin-4-ol Chemical compound NN1C=NC2=CC=C(C=C2C1(C1=CC=CC=C1)O)C(F)(F)F AXPOBLRMPCKWIT-UHFFFAOYSA-N 0.000 description 3
- BXBSDHSVTCGOFC-UHFFFAOYSA-N 3-amino-4-phenylquinazolin-4-ol Chemical compound NN1C=NC2=CC=CC=C2C1(O)C1=CC=CC=C1 BXBSDHSVTCGOFC-UHFFFAOYSA-N 0.000 description 3
- BQFFHUASKUKCMD-UHFFFAOYSA-N 3-amino-6-chloro-4-(2-chlorophenyl)quinazolin-4-ol Chemical compound NN1C=NC2=CC=C(Cl)C=C2C1(O)C1=CC=CC=C1Cl BQFFHUASKUKCMD-UHFFFAOYSA-N 0.000 description 3
- IIEZZJWHRMCMML-UHFFFAOYSA-N 3-amino-6-chloro-4-(2-fluorophenyl)quinazolin-4-ol Chemical compound NN1C=NC2=CC=C(C=C2C1(O)C1=C(C=CC=C1)F)Cl IIEZZJWHRMCMML-UHFFFAOYSA-N 0.000 description 3
- WQXVDQYPSMONGQ-UHFFFAOYSA-N 3-amino-6-chloro-4-(4-methoxyphenyl)quinazolin-4-ol Chemical compound NN1C=NC2=CC=C(C=C2C1(C1=CC=C(C=C1)OC)O)Cl WQXVDQYPSMONGQ-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DVJBEKKCYUFDDM-UHFFFAOYSA-N [2-[3-(chloromethyl)-1,2,4-triazol-4-yl]phenyl]-phenylmethanone Chemical compound ClCC1=NN=CN1C1=C(C(=O)C2=CC=CC=C2)C=CC=C1 DVJBEKKCYUFDDM-UHFFFAOYSA-N 0.000 description 3
- CPBUCUDVFXOMHN-UHFFFAOYSA-N [5-chloro-2-[3-(chloromethyl)-5-methyl-1,2,4-triazol-4-yl]phenyl]-phenylmethanone Chemical compound CC1=NN=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 CPBUCUDVFXOMHN-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- GSIGZZKHXAAYOA-UHFFFAOYSA-N 6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC=CC=C2N2C=NN=C2CN=C1C1=CC=CC=C1 GSIGZZKHXAAYOA-UHFFFAOYSA-N 0.000 description 2
- NDKNGRSHIXOUBH-UHFFFAOYSA-N 6-phenyl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(C(F)(F)F)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 NDKNGRSHIXOUBH-UHFFFAOYSA-N 0.000 description 2
- AHFSVSXBGSYAKI-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound FC1=CC=CC=C1C1=NCC2=NN=CN2C2=CC=C(Cl)C=C12 AHFSVSXBGSYAKI-UHFFFAOYSA-N 0.000 description 2
- MBWHYICJBGVYJE-UHFFFAOYSA-N 8-nitro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C([N+](=O)[O-])=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 MBWHYICJBGVYJE-UHFFFAOYSA-N 0.000 description 2
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- WADQPAMHVOGKMH-UHFFFAOYSA-N [2-[3-(chloromethyl)-1,2,4-triazol-4-yl]-5-nitrophenyl]-phenylmethanone Chemical compound ClCC1=NN=CN1C1=C(C(=O)C2=CC=CC=C2)C=C(C=C1)[N+](=O)[O-] WADQPAMHVOGKMH-UHFFFAOYSA-N 0.000 description 2
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- HMBRVDQHILYKRN-UHFFFAOYSA-N ClC=1C=CC(=C(C(=O)C2=CC=C(C=C2)OC)C=1)NC=O Chemical compound ClC=1C=CC(=C(C(=O)C2=CC=C(C=C2)OC)C=1)NC=O HMBRVDQHILYKRN-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VKZCTTHJHCDIAM-UHFFFAOYSA-N N'-(2-benzoyl-4-methylphenyl)-N,N-dimethylmethanimidamide Chemical compound CN(C)C=NC1=C(C(=O)C2=CC=CC=C2)C=C(C=C1)C VKZCTTHJHCDIAM-UHFFFAOYSA-N 0.000 description 1
- WBXXIQDTKCKNTG-UHFFFAOYSA-N N'-(2-benzoyl-4-nitrophenyl)-N,N-dimethylmethanimidamide Chemical compound CN(C)C=NC1=C(C(=O)C2=CC=CC=C2)C=C(C=C1)[N+](=O)[O-] WBXXIQDTKCKNTG-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CNCSRKWHUULEDB-UHFFFAOYSA-N [2-[3-(chloromethyl)-1,2,4-triazol-4-yl]-5-(trifluoromethyl)phenyl]-phenylmethanone Chemical compound FC(F)(F)C1=CC(C(=O)C2=CC=CC=C2)=C(C=C1)N1C=NN=C1CCl CNCSRKWHUULEDB-UHFFFAOYSA-N 0.000 description 1
- KBWXJZXYNPXORC-UHFFFAOYSA-N [5-chloro-2-[3-(chloromethyl)-1,2,4-triazol-4-yl]phenyl]-phenylmethanone Chemical compound ClCC1=NN=CN1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 KBWXJZXYNPXORC-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
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- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229940024874 benzophenone Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001896 cresols Chemical class 0.000 description 1
- CDCHDCWJMGXXRH-UHFFFAOYSA-N estazolam Chemical compound C=1C(Cl)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 CDCHDCWJMGXXRH-UHFFFAOYSA-N 0.000 description 1
- XCPXPFNKTCFWTA-UHFFFAOYSA-N ethyl carbonobromidate Chemical compound CCOC(Br)=O XCPXPFNKTCFWTA-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- AOZBUHWFXIOKQF-UHFFFAOYSA-N ethyl n-(2-benzoyl-4-chlorophenyl)ethanimidate Chemical compound CCOC(C)=NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 AOZBUHWFXIOKQF-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- FPFNOZQDAQHPOZ-UHFFFAOYSA-N n-(2-benzoylphenyl)formamide Chemical compound O=CNC1=CC=CC=C1C(=O)C1=CC=CC=C1 FPFNOZQDAQHPOZ-UHFFFAOYSA-N 0.000 description 1
- KFVXLXMEIIIXKS-UHFFFAOYSA-N n-[4-chloro-2-(2-chlorobenzoyl)phenyl]formamide Chemical compound ClC1=CC=C(NC=O)C(C(=O)C=2C(=CC=CC=2)Cl)=C1 KFVXLXMEIIIXKS-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- KYTREVLPRJOBEM-UHFFFAOYSA-N triazolo[4,5-i][1,2]benzodiazepine Chemical class C1=CC2=CC=CN=NC2=C2C1=NN=N2 KYTREVLPRJOBEM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8867570A JPS4925952B1 (xx) | 1970-10-07 | 1970-10-07 | |
| JP4362471A JPS5421352B1 (xx) | 1971-06-17 | 1971-06-17 | |
| JP6994971A JPS5246959B2 (xx) | 1971-09-08 | 1971-09-08 | |
| CH1463671A CH563392A5 (en) | 1970-10-07 | 1971-10-07 | Substd 4h s-triazolo (43-a)(1 4) benzodiazepins - from 2-(3-halomethy s-triazol-4-yl) benzophenones and ammonia or hexamethylene tetramine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH572484A5 true CH572484A5 (en) | 1976-02-13 |
Family
ID=27429580
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1074873A CH562814A5 (xx) | 1970-10-07 | 1971-10-07 | |
| CH1480874A CH572484A5 (en) | 1970-10-07 | 1971-10-07 | Substd 4h s-triazolo (43-a)(1 4) benzodiazepins - from 2-(3-halomethy s-triazol-4-yl) benzophenones and ammonia or hexamethylene tetramine |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1074873A CH562814A5 (xx) | 1970-10-07 | 1971-10-07 |
Country Status (1)
| Country | Link |
|---|---|
| CH (2) | CH562814A5 (xx) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107721939A (zh) * | 2017-11-09 | 2018-02-23 | 华中药业股份有限公司 | 5‑氯‑2‑（3‑氯甲基‑s‑三氮唑基）二苯酮盐酸盐的制备方法 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111689913B (zh) * | 2019-03-11 | 2023-03-28 | 浙江医药股份有限公司新昌制药厂 | 5-氯-2-(3-氯甲基-s-三氮唑基)二苯甲酮的氯乙酸盐及其晶型和制备方法 |
-
1971
- 1971-10-07 CH CH1074873A patent/CH562814A5/de not_active IP Right Cessation
- 1971-10-07 CH CH1480874A patent/CH572484A5/de not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107721939A (zh) * | 2017-11-09 | 2018-02-23 | 华中药业股份有限公司 | 5‑氯‑2‑（3‑氯甲基‑s‑三氮唑基）二苯酮盐酸盐的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CH562814A5 (xx) | 1975-06-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |