CA1050021A - Aza-6 3h-1 benzodiazepines-4 - Google Patents

Aza-6 3h-1 benzodiazepines-4

Info

Publication number: CA1050021A
Authority: CA; Canada
Prior art keywords: group; alkyl; amino; hydrogen; compound
Prior art date: 1968-03-08
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA198,389A

Other languages

English (en)

Other versions

CA198389S (en

Inventor

Walter Von Bebenburg

Heribert Offermanns

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Evonik Operations GmbH

Original Assignee

Deutsche Gold und Silber Scheideanstalt

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1968-03-08

Filing date

1974-04-29

Publication date

1979-03-06

1968-03-08 Priority claimed from AT3772A external-priority patent/AT304473B/de

1974-04-29 Application filed by Deutsche Gold und Silber Scheideanstalt filed Critical Deutsche Gold und Silber Scheideanstalt

1979-03-06 Application granted granted Critical

1979-03-06 Publication of CA1050021A publication Critical patent/CA1050021A/fr

Status Expired legal-status Critical Current

Links

BTQDZLVHRYXJDK-UHFFFAOYSA-N 3h-pyrido[3,2-e][1,4]diazepine Chemical class C1=NCC=NC2=CC=CN=C21 BTQDZLVHRYXJDK-UHFFFAOYSA-N 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 83
238000000034 method Methods 0.000 claims abstract description 57
-1 piperazino Chemical group 0.000 claims abstract description 42
239000002253 acid Substances 0.000 claims abstract description 34
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
239000001257 hydrogen Substances 0.000 claims abstract description 31
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 27
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
150000003839 salts Chemical class 0.000 claims abstract description 19
125000005843 halogen group Chemical group 0.000 claims abstract description 14
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 8
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000005191 hydroxyalkylamino group Chemical group 0.000 claims abstract description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 7
125000003282 alkyl amino group Chemical group 0.000 claims abstract 4
WWLXTFAUHIGYMY-UHFFFAOYSA-N 5-phenyl-1,3-dihydropyrido[3,2-e][1,4]diazepin-2-one Chemical class C12=NC=CC=C2NC(=O)CN=C1C1=CC=CC=C1 WWLXTFAUHIGYMY-UHFFFAOYSA-N 0.000 claims abstract 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 35
239000000126 substance Substances 0.000 claims description 34
239000000460 chlorine Chemical group 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 31
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
229910052801 chlorine Inorganic materials 0.000 claims description 21
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 20
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
125000003277 amino group Chemical group 0.000 claims description 15
239000000376 reactant Substances 0.000 claims description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
229910021529 ammonia Inorganic materials 0.000 claims description 13
229910052731 fluorine Inorganic materials 0.000 claims description 11
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
239000011737 fluorine Chemical group 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 8
125000002252 acyl group Chemical group 0.000 claims description 8
229910052794 bromium Chemical group 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
239000012312 sodium hydride Substances 0.000 claims description 8
229910000104 sodium hydride Inorganic materials 0.000 claims description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
238000010992 reflux Methods 0.000 claims description 6
229960000583 acetic acid Drugs 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
238000005984 hydrogenation reaction Methods 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
150000003254 radicals Chemical class 0.000 claims description 5
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical group 0.000 claims description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
238000009835 boiling Methods 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
159000000000 sodium salts Chemical class 0.000 claims description 3
XXANBILMPMODEO-UHFFFAOYSA-N [3-amino-6-(dimethylamino)pyridin-2-yl]-phenylmethanone Chemical compound CN(C)C1=CC=C(N)C(C(=O)C=2C=CC=CC=2)=N1 XXANBILMPMODEO-UHFFFAOYSA-N 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 claims description 2
239000011230 binding agent Substances 0.000 claims description 2
238000009833 condensation Methods 0.000 claims description 2
230000005494 condensation Effects 0.000 claims description 2
239000012362 glacial acetic acid Substances 0.000 claims description 2
229910000042 hydrogen bromide Inorganic materials 0.000 claims description 2
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
239000012299 nitrogen atmosphere Substances 0.000 claims 2
CPEONABTMRSIKA-UHFFFAOYSA-N 1,4$l^{2}-oxazinane Chemical compound C1COCC[N]1 CPEONABTMRSIKA-UHFFFAOYSA-N 0.000 claims 1
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 claims 1
CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 claims 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
208000019901 Anxiety disease Diseases 0.000 abstract description 4
230000000694 effects Effects 0.000 abstract description 4
230000036506 anxiety Effects 0.000 abstract description 2
238000002360 preparation method Methods 0.000 abstract description 2
RHUHLVLFKDUQLC-UHFFFAOYSA-N 2,3-dihydro-1h-pyrido[3,2-e][1,4]diazepine Chemical class N1CCN=CC2=NC=CC=C21 RHUHLVLFKDUQLC-UHFFFAOYSA-N 0.000 abstract 1
230000001603 reducing effect Effects 0.000 abstract 1
239000000243 solution Substances 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 15
238000003756 stirring Methods 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
238000007792 addition Methods 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
239000000047 product Substances 0.000 description 10
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 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000013543 active substance Substances 0.000 description 9
239000003814 drug Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
239000003513 alkali Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
239000007858 starting material Substances 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
150000001298 alcohols Chemical class 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
229940079593 drug Drugs 0.000 description 7
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
229960001760 dimethyl sulfoxide Drugs 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
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 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
238000001816 cooling Methods 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000011734 sodium Substances 0.000 description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001339 alkali metal compounds Chemical class 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
239000002585 base Substances 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000000875 corresponding effect Effects 0.000 description 4
239000002270 dispersing agent Substances 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
150000002828 nitro derivatives Chemical class 0.000 description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
239000001913 cellulose Chemical class 0.000 description 3
229920002678 cellulose Chemical class 0.000 description 3
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
230000002349 favourable effect Effects 0.000 description 3
239000000945 filler Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
235000011187 glycerol Nutrition 0.000 description 3
235000010299 hexamethylene tetramine Nutrition 0.000 description 3
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
229940072033 potash Drugs 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
238000006748 scratching Methods 0.000 description 3
230000002393 scratching effect Effects 0.000 description 3
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 3
235000011121 sodium hydroxide Nutrition 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000000967 suction filtration Methods 0.000 description 3
150000003512 tertiary amines Chemical class 0.000 description 3
239000011732 tocopherol Substances 0.000 description 3
229930003799 tocopherol Natural products 0.000 description 3
235000019149 tocopherols Nutrition 0.000 description 3
QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 3
XKSSANWPTUFBLD-UHFFFAOYSA-N (6-amino-3-nitropyridin-2-yl)-phenylmethanone Chemical compound NC1=CC=C([N+]([O-])=O)C(C(=O)C=2C=CC=CC=2)=N1 XKSSANWPTUFBLD-UHFFFAOYSA-N 0.000 description 2
SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
229910010084 LiAlH4 Inorganic materials 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
238000000297 Sandmeyer reaction Methods 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
229910000102 alkali metal hydride Inorganic materials 0.000 description 2
150000008046 alkali metal hydrides Chemical class 0.000 description 2
150000001447 alkali salts Chemical class 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
150000001555 benzenes Chemical class 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
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125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
239000001814 pectin Substances 0.000 description 1
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229920001277 pectin Polymers 0.000 description 1
WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
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230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
229960003424 phenylacetic acid Drugs 0.000 description 1
239000003279 phenylacetic acid Substances 0.000 description 1
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical class N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
125000005543 phthalimide group Chemical class 0.000 description 1
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229910052697 platinum Inorganic materials 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
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108090000765 processed proteins & peptides Proteins 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
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
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
150000004671 saturated fatty acids Chemical class 0.000 description 1
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 1
230000035939 shock Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
150000003388 sodium compounds Chemical class 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000003860 storage Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
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
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
150000004670 unsaturated fatty acids Chemical class 0.000 description 1
235000021122 unsaturated fatty acids Nutrition 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA198,389A 1968-03-08 1974-04-29 Aza-6 3h-1 benzodiazepines-4 Expired CA1050021A (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
AT3772A AT304473B (de)	1967-03-10	1968-03-08	Verfahren zur Herstellung von neuen substituierten 1-Amino-2-hydroxy-3-[2'-cyclopentyl- bzw. (δ<2>-cyclopentenyl)-phenoxy]-propanen, deren optisch aktiven Isomeren und Salzen

Publications (1)

Publication Number	Publication Date
CA1050021A true CA1050021A (fr)	1979-03-06

Family

ID=3555215

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA198,389A Expired CA1050021A (fr)	1968-03-08	1974-04-29	Aza-6 3h-1 benzodiazepines-4

Country Status (1)

Country	Link
CA (1)	CA1050021A (fr)

1974
- 1974-04-29 CA CA198,389A patent/CA1050021A/fr not_active Expired

Publication	Publication Date	Title
AU677644B2 (en)	1997-05-01	Piperazine derivatives
US4186199A (en)	1980-01-29	Indolo-,1,2-dihydroindolo-, and 1,2,6,7-tetrahydroindolo [1,7-ab][1,5] benzodiazepines
JPH06507182A (ja)	1994-08-11	Ｎ−スルホニル−２−オキソインドール誘導体、それらの製造、及びそれらが存在する薬学的組成物
JPH04230377A (ja)	1992-08-19	１−インドリルアルキル−４−（アルコキシピリミジニル）ピペラジン
EP0167901B1 (fr)	1990-04-04	Composés actifs
US3317524A (en)	1967-05-02	Substituted 1, 2, 3, 4-tetrahydro-pyrazino[1, 2-a]indoles
US4080330A (en)	1978-03-21	Phenylindolines and process for their production
GB1581500A (en)	1980-12-17	Pyridobenzodiazepines
EP0012208A2 (fr)	1980-06-25	9-(3-(3,5-cis-Diméthylpipérazino)propyl)-carbazole, sa préparation et ses compositions pharmaceutiques
TWI290554B (en)	2007-12-01	Process for preparation 5-(1-piperazinyl)-benzofuran-2-carboxamide by transition metal-catalyzed amination
GB2120662A (en)	1983-12-07	New azepinoindoles, their production and pharmaceutical compositions containing them
US3468894A (en)	1969-09-23	Certain 2-pyridyl-substituted indole derivatives
EP0233413B1 (fr)	1993-05-05	Dérivés de 3-(2-aminoéthyl)indole et -indoline, procédés pour leur préparation et compositions pharmaceutiques les contenant
JPS6047255B2 (ja)	1985-10-21	２−アミノ−５−スルフアモイル−安息香酸アミドの製法
CA1050021A (fr)	1979-03-06	Aza-6 3h-1 benzodiazepines-4
IL26724A (en)	1970-11-30	Benzodiazepine derivatives and process for the manufacture thereof
HU206502B (en)	1992-11-30	Process for producing new pyridobenzoindol derivatives and pharmaceutical compositions containing them
KR100382998B1 (ko)	2003-08-27	6-메톡시-1h-벤조트리아졸-5-카르복사미드유도체,그제조방법및그것을함유하는의약조성물
KR870000279B1 (ko)	1987-02-23	피리도 [1,4] 벤조디아제핀 및 [2-[(니트로피리디닐) 아미노]페닐] 아릴메타논의 제조방법
EP0743946A1 (fr)	1996-11-27	Indoles condenses a titre d'antagonistes des recepteurs de 5ht 2b?
KR930006777B1 (ko)	1993-07-23	피리도[1,2-a]인돌 화합물 및 그 제조방법
US4874761A (en)	1989-10-17	4-arylcarbonyl-1-[(4-morpholinyl)-lower-alkyl]-1H-indoles
EP0278265B1 (fr)	1992-09-09	[(Morpholinyl-4)alkyl]-1 1H-indoles utilisables comme analgésiques et leur préparation
NZ231370A (en)	1992-03-26	1,3-benzodiazepin-2-one derivatives, medicaments
JPH0764843B2 (ja)	1995-07-12	新規化合物，その製法及びそれを含む医薬組成物