CH633555A5 - Verfahren zur herstellung von 1-(2-(dialkylamino)aethyl)-6-aryl-4h-s-triazolo(4,3-a)(1,4)benzodiazepinen. - Google Patents
Verfahren zur herstellung von 1-(2-(dialkylamino)aethyl)-6-aryl-4h-s-triazolo(4,3-a)(1,4)benzodiazepinen. Download PDFInfo
- Publication number
- CH633555A5 CH633555A5 CH49078A CH49078A CH633555A5 CH 633555 A5 CH633555 A5 CH 633555A5 CH 49078 A CH49078 A CH 49078A CH 49078 A CH49078 A CH 49078A CH 633555 A5 CH633555 A5 CH 633555A5
- Authority
- CH
- Switzerland
- Prior art keywords
- radical
- formula
- phenyl
- triazolo
- ammonium salt
- Prior art date
Links
- 229940049706 benzodiazepine Drugs 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001557 benzodiazepines Chemical class 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 claims description 61
- 238000006243 chemical reaction Methods 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 37
- 239000000047 product Substances 0.000 claims description 35
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 33
- 150000001875 compounds Chemical class 0.000 claims description 33
- 239000003795 chemical substances by application Substances 0.000 claims description 30
- -1 alkyl radical Chemical class 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 26
- VGIVLIHKENZQHQ-UHFFFAOYSA-N n,n,n',n'-tetramethylmethanediamine Chemical compound CN(C)CN(C)C VGIVLIHKENZQHQ-UHFFFAOYSA-N 0.000 claims description 20
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 239000007858 starting material Substances 0.000 claims description 14
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 13
- 150000003863 ammonium salts Chemical class 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 9
- 238000011065 in-situ storage Methods 0.000 claims description 9
- XDAGXZXKTKRFMT-UHFFFAOYSA-N propan-2-imine Chemical class CC(C)=N XDAGXZXKTKRFMT-UHFFFAOYSA-N 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 7
- QWEJEQQJNBKACP-UHFFFAOYSA-N 2-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-dimethylethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=CC=CC=C1 QWEJEQQJNBKACP-UHFFFAOYSA-N 0.000 claims description 6
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 claims description 4
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- HYHSFFFCLDOXCJ-UHFFFAOYSA-N dimethyl(methylidene)azanium Chemical class C[N+](C)=C HYHSFFFCLDOXCJ-UHFFFAOYSA-N 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 79
- 239000000243 solution Substances 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- UNEXJVCWJSHFNN-UHFFFAOYSA-N n,n,n',n'-tetraethylmethanediamine Chemical compound CCN(CC)CN(CC)CC UNEXJVCWJSHFNN-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- GDOPCQJETORZLN-UHFFFAOYSA-N 2-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-dimethylethanamine;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C12=CC(Cl)=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=CC=CC=C1 GDOPCQJETORZLN-UHFFFAOYSA-N 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000008065 acid anhydrides Chemical class 0.000 description 3
- 239000012042 active reagent Substances 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- MTXLEPSPXBBNLP-UHFFFAOYSA-N 1-methyl-8-methylsulfanyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(SC)=CC=C(N2C(C)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 MTXLEPSPXBBNLP-UHFFFAOYSA-N 0.000 description 2
- QKDJZBFTBRCUSN-UHFFFAOYSA-N 2-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-dimethylpropan-1-amine Chemical class C12=CC(Cl)=CC=C2N2C(C(CN(C)C)C)=NN=C2CN=C1C1=CC=CC=C1 QKDJZBFTBRCUSN-UHFFFAOYSA-N 0.000 description 2
- LTWBLRDEWCYARL-UHFFFAOYSA-N 2-[8-bromo-6-(2-fluorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-diethylethanamine Chemical compound C12=CC(Br)=CC=C2N2C(CCN(CC)CC)=NN=C2CN=C1C1=CC=CC=C1F LTWBLRDEWCYARL-UHFFFAOYSA-N 0.000 description 2
- LKRNZLYYWVHIFZ-UHFFFAOYSA-N 4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical class C1N=CC2=CC=CC=C2N2C=NN=C12 LKRNZLYYWVHIFZ-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- WXXNJRUZESCGOO-UHFFFAOYSA-N n,n-diethyl-2-(8-methylsulfanyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound C12=CC(SC)=CC=C2N2C(CCN(CC)CC)=NN=C2CN=C1C1=CC=CC=C1 WXXNJRUZESCGOO-UHFFFAOYSA-N 0.000 description 2
- GMPWGVYHXTYWHZ-UHFFFAOYSA-N n,n-dimethyl-2-[6-phenyl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=CC=CC=C1 GMPWGVYHXTYWHZ-UHFFFAOYSA-N 0.000 description 2
- DNCLKIRATPITAI-UHFFFAOYSA-N n-propyl-n-[2-[6-pyridin-2-yl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]ethyl]propan-1-amine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(CCN(CCC)CCC)=NN=C2CN=C1C1=CC=CC=N1 DNCLKIRATPITAI-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DWPZNZAUIXWVRE-UHFFFAOYSA-N 1-benzyl-8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(Cl)=CC=C(N23)C=1C(C=1C=CC=CC=1)=NCC3=NN=C2CC1=CC=CC=C1 DWPZNZAUIXWVRE-UHFFFAOYSA-N 0.000 description 1
- BTYFPUAHZUNPRP-UHFFFAOYSA-N 1-methyl-6-phenyl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 BTYFPUAHZUNPRP-UHFFFAOYSA-N 0.000 description 1
- CQSMMGVQIXHMDI-UHFFFAOYSA-N 1-methyl-6-phenyl-9-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC=C(C(F)(F)F)C=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 CQSMMGVQIXHMDI-UHFFFAOYSA-N 0.000 description 1
- ZRVXWGCGORLVLM-UHFFFAOYSA-N 1-methyl-6-pyridin-2-yl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=N1 ZRVXWGCGORLVLM-UHFFFAOYSA-N 0.000 description 1
- SYAWZZSURNSENY-UHFFFAOYSA-N 1-methyl-8-methylsulfanyl-6-pyridin-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(SC)=CC=C(N2C(C)=NN=C2CN=2)C=1C=2C1=CC=CC=N1 SYAWZZSURNSENY-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- WZTHRMQUAKWTDP-UHFFFAOYSA-N 1h-1,2-benzodiazepine;2h-triazole Chemical compound C1=CNN=N1.N1N=CC=CC2=CC=CC=C12 WZTHRMQUAKWTDP-UHFFFAOYSA-N 0.000 description 1
- LGNWUMGEJQAWQD-UHFFFAOYSA-N 1h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound N1=CC2=CC=CC=C2N2CN=NC2=C1 LGNWUMGEJQAWQD-UHFFFAOYSA-N 0.000 description 1
- BVZVBNNXMHPZKK-UHFFFAOYSA-N 2-(8-bromo-6-pyridin-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-dimethylethanamine Chemical compound C12=CC(Br)=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=CC=CC=N1 BVZVBNNXMHPZKK-UHFFFAOYSA-N 0.000 description 1
- TVVGHIMPVNDKGE-UHFFFAOYSA-N 2-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-diethylethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CCN(CC)CC)=NN=C2CN=C1C1=CC=CC=C1 TVVGHIMPVNDKGE-UHFFFAOYSA-N 0.000 description 1
- OXNRPSGQEPITJC-UHFFFAOYSA-N 2-(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-dimethyl-2-phenylethanamine Chemical class C=1C=CC=CC=1C(CN(C)C)C(N1C2=CC=C(Cl)C=C22)=NN=C1CN=C2C1=CC=CC=C1 OXNRPSGQEPITJC-UHFFFAOYSA-N 0.000 description 1
- IAIOIYKAUWTSNT-UHFFFAOYSA-N 2-(8-chloro-6-pyridin-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)-n,n-diethylethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CCN(CC)CC)=NN=C2CN=C1C1=CC=CC=N1 IAIOIYKAUWTSNT-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- QTNNSLBGBXWESJ-UHFFFAOYSA-N 2-[7-chloro-6-(2-chlorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylethanamine Chemical compound C12=C(Cl)C=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=CC=CC=C1Cl QTNNSLBGBXWESJ-UHFFFAOYSA-N 0.000 description 1
- OUFVNMHKITWCFU-UHFFFAOYSA-N 2-[8-chloro-6-(2,6-difluorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=C(F)C=CC=C1F OUFVNMHKITWCFU-UHFFFAOYSA-N 0.000 description 1
- KPSPFGAWJNVQRV-UHFFFAOYSA-N 2-[8-chloro-6-(2-chlorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CCN(C)C)=NN=C2CN=C1C1=CC=CC=C1Cl KPSPFGAWJNVQRV-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- DXXHRZUOTPMGEH-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)propanoic acid Chemical compound C1=CC=C2C(=O)N(CCC(=O)O)C(=O)C2=C1 DXXHRZUOTPMGEH-UHFFFAOYSA-N 0.000 description 1
- JLIFZFWTAZANFG-UHFFFAOYSA-N 7-chloro-6-(2-chlorophenyl)-1-methyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=C(Cl)C=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JLIFZFWTAZANFG-UHFFFAOYSA-N 0.000 description 1
- WREQLXVWPBXFFI-UHFFFAOYSA-N 8-chloro-1-ethyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N2C(CC)=NN=C2CN=C1C1=CC=CC=C1 WREQLXVWPBXFFI-UHFFFAOYSA-N 0.000 description 1
- KYLFESWNOKEJCE-UHFFFAOYSA-N 8-chloro-1-methyl-6-pyridin-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=N1 KYLFESWNOKEJCE-UHFFFAOYSA-N 0.000 description 1
- BLZPMGPKYFCTIZ-UHFFFAOYSA-N 8-fluoro-6-(2-fluorophenyl)-1-methyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C12=CC(F)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1F BLZPMGPKYFCTIZ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-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
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000001914 calming effect Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- VXGSZBZQCBNUIP-UHFFFAOYSA-N flubromazolam Chemical compound C12=CC(Br)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1F VXGSZBZQCBNUIP-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- LVQVCXWUIXUPOH-UHFFFAOYSA-N n,n-diethyl-2-[6-phenyl-9-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]ethanamine Chemical compound C12=CC=C(C(F)(F)F)C=C2N2C(CCN(CC)CC)=NN=C2CN=C1C1=CC=CC=C1 LVQVCXWUIXUPOH-UHFFFAOYSA-N 0.000 description 1
- BPVXGQWKISXWPJ-UHFFFAOYSA-N n,n-dimethyl-2-(8-methylsulfanyl-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)ethanamine Chemical compound C=1C(SC)=CC=C(N2C(CCN(C)C)=NN=C2CN=2)C=1C=2C1=CC=CC=C1 BPVXGQWKISXWPJ-UHFFFAOYSA-N 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- TXCQKYYHJNPJIR-UHFFFAOYSA-N n-[2-(8-methylsulfanyl-6-pyridin-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)ethyl]-n-propylpropan-1-amine Chemical compound C12=CC(SC)=CC=C2N2C(CCN(CCC)CCC)=NN=C2CN=C1C1=CC=CC=N1 TXCQKYYHJNPJIR-UHFFFAOYSA-N 0.000 description 1
- IFDOBXDDBDYFQR-UHFFFAOYSA-N n-[2-(8-nitro-6-pyridin-2-yl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)ethyl]-n-propylpropan-1-amine Chemical compound C12=CC([N+]([O-])=O)=CC=C2N2C(CCN(CCC)CCC)=NN=C2CN=C1C1=CC=CC=N1 IFDOBXDDBDYFQR-UHFFFAOYSA-N 0.000 description 1
- RRLUPWLQXBDGHZ-UHFFFAOYSA-N n-[2-[8-fluoro-6-(2-fluorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]ethyl]-n-propylpropan-1-amine Chemical compound C12=CC(F)=CC=C2N2C(CCN(CCC)CCC)=NN=C2CN=C1C1=CC=CC=C1F RRLUPWLQXBDGHZ-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- FEQAUBVIUZJXKN-UHFFFAOYSA-N propan-2-imine;hydrochloride Chemical compound [Cl-].CC(C)=[NH2+] FEQAUBVIUZJXKN-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical class 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 description 1
- KYTREVLPRJOBEM-UHFFFAOYSA-N triazolo[4,5-i][1,2]benzodiazepine Chemical compound C1=CC2=CC=CN=NC2=C2C1=NN=N2 KYTREVLPRJOBEM-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/761,803 US4075221A (en) | 1977-01-24 | 1977-01-24 | Process for preparing triazolobenzodiazepines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH633555A5 true CH633555A5 (de) | 1982-12-15 |
Family
ID=25063310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH49078A CH633555A5 (de) | 1977-01-24 | 1978-01-17 | Verfahren zur herstellung von 1-(2-(dialkylamino)aethyl)-6-aryl-4h-s-triazolo(4,3-a)(1,4)benzodiazepinen. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4075221A (en:Method) |
| JP (1) | JPS5392797A (en:Method) |
| AU (1) | AU512354B2 (en:Method) |
| BE (1) | BE863254A (en:Method) |
| CH (1) | CH633555A5 (en:Method) |
| DE (1) | DE2801241A1 (en:Method) |
| FR (1) | FR2378033A1 (en:Method) |
| GB (1) | GB1563578A (en:Method) |
| NL (1) | NL7800487A (en:Method) |
| ZA (1) | ZA777719B (en:Method) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4689413A (en) * | 1983-03-17 | 1987-08-25 | The Upjohn Company | Triazolo-benzodiazepine-1-ethanamines as diuretics |
| US4514407A (en) * | 1983-03-17 | 1985-04-30 | The Upjohn Company | 1-Ethanamine-triazolo-benzodiazepines as diuretics |
| US4474699A (en) * | 1983-05-25 | 1984-10-02 | The Upjohn Company | Preparing 1-aminomethyl-6-substituted-4H-s-triazolo[4,3-a][1,4]benzodiazepines in improved procedures |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3759943A (en) * | 1971-04-28 | 1973-09-18 | Upjohn Co | Amido and amino triazolo benzodiazepines |
| US4001262A (en) * | 1975-10-20 | 1977-01-04 | The Upjohn Company | Process for the production of 1-[(dimethylamino)methyl]-6-phenyl-4H-triazolo[4,3-a][1,4]-benzodiazepine |
-
1977
- 1977-01-24 US US05/761,803 patent/US4075221A/en not_active Expired - Lifetime
- 1977-12-15 GB GB52181/77A patent/GB1563578A/en not_active Expired
- 1977-12-29 ZA ZA00777719A patent/ZA777719B/xx unknown
-
1978
- 1978-01-09 AU AU32251/78A patent/AU512354B2/en not_active Expired
- 1978-01-12 JP JP234378A patent/JPS5392797A/ja active Pending
- 1978-01-12 DE DE19782801241 patent/DE2801241A1/de not_active Withdrawn
- 1978-01-16 NL NL7800487A patent/NL7800487A/xx not_active Application Discontinuation
- 1978-01-17 CH CH49078A patent/CH633555A5/de not_active IP Right Cessation
- 1978-01-23 FR FR7801828A patent/FR2378033A1/fr active Granted
- 1978-01-24 BE BE184586A patent/BE863254A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ZA777719B (en) | 1978-10-25 |
| NL7800487A (nl) | 1978-07-26 |
| GB1563578A (en) | 1980-03-26 |
| JPS5392797A (en) | 1978-08-15 |
| FR2378033A1 (fr) | 1978-08-18 |
| US4075221A (en) | 1978-02-21 |
| AU512354B2 (en) | 1980-10-09 |
| FR2378033B1 (en:Method) | 1983-02-04 |
| AU3225178A (en) | 1979-07-19 |
| BE863254A (fr) | 1978-07-24 |
| DE2801241A1 (de) | 1978-07-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |