CA1077475A - Process for production of substituted 6-aryl-4h-s-triazolo-(3,4-c)-thieno-(2,3-e)-1,4-diazepines and intermediates - Google Patents
Process for production of substituted 6-aryl-4h-s-triazolo-(3,4-c)-thieno-(2,3-e)-1,4-diazepines and intermediatesInfo
- Publication number
- CA1077475A CA1077475A CA257,092A CA257092A CA1077475A CA 1077475 A CA1077475 A CA 1077475A CA 257092 A CA257092 A CA 257092A CA 1077475 A CA1077475 A CA 1077475A
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- thieno
- chlorine
- chlorophenyl
- Prior art date
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 61
- 239000000543 intermediate Substances 0.000 title abstract description 6
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- -1 alkali metal alkoxide Chemical class 0.000 claims description 62
- 238000006243 chemical reaction Methods 0.000 claims description 47
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 43
- 229910052801 chlorine Inorganic materials 0.000 claims description 42
- 239000000460 chlorine Substances 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000005936 piperidyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 238000005658 halogenation reaction Methods 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 230000026030 halogenation Effects 0.000 claims description 7
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 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 claims description 5
- YAGNKIVRNNJVQI-UHFFFAOYSA-N 2-chloro-n-[3-[(2-chlorophenyl)-hydroxymethyl]thiophen-2-yl]acetamide Chemical compound C=1C=CC=C(Cl)C=1C(O)C=1C=CSC=1NC(=O)CCl YAGNKIVRNNJVQI-UHFFFAOYSA-N 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 claims description 4
- 239000011574 phosphorus Substances 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- BBBPUTKOKSMZSN-UHFFFAOYSA-N 7-bromo-5-(2-chlorophenyl)thieno[3,2-f][1,4]oxazepine 8-oxide Chemical compound ClC1=CC=CC=C1C1=NC=COC2=C1C=C(Br)S2=O BBBPUTKOKSMZSN-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 241001061127 Thione Species 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 229910001503 inorganic bromide Inorganic materials 0.000 claims description 3
- 229910001504 inorganic chloride Inorganic materials 0.000 claims description 3
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 10
- 230000000875 corresponding effect Effects 0.000 claims 8
- 125000004149 thio group Chemical group *S* 0.000 claims 5
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims 2
- BAHIUTZHSPYTRB-UHFFFAOYSA-N 5-(2-chlorophenyl)thieno[3,2-f][1,4]oxazepine 8-oxide Chemical compound ClC1=C(C=CC=C1)C=1C2=C(OC=CN1)S(C=C2)=O BAHIUTZHSPYTRB-UHFFFAOYSA-N 0.000 claims 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- 150000001450 anions Chemical class 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- WUENQAXGJXBDJD-UHFFFAOYSA-N n-[3-[(2-bromophenyl)-hydroxymethyl]thiophen-2-yl]-2-chloroacetamide Chemical compound C=1C=CC=C(Br)C=1C(O)C=1C=CSC=1NC(=O)CCl WUENQAXGJXBDJD-UHFFFAOYSA-N 0.000 claims 1
- 230000002539 anti-aggressive effect Effects 0.000 abstract description 2
- 230000002082 anti-convulsion Effects 0.000 abstract description 2
- 239000002249 anxiolytic agent Substances 0.000 abstract description 2
- 230000000949 anxiolytic effect Effects 0.000 abstract description 2
- 210000003205 muscle Anatomy 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 10
- 238000006356 dehydrogenation reaction Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- 239000011651 chromium Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000011572 manganese Substances 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 150000007530 organic bases Chemical group 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- JHWIEAWILPSRMU-UHFFFAOYSA-N 2-methyl-3-pyrimidin-4-ylpropanoic acid Chemical compound OC(=O)C(C)CC1=CC=NC=N1 JHWIEAWILPSRMU-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 229910052748 manganese Inorganic materials 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000011369 resultant mixture Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- SZCYCMXUEPXTPW-UHFFFAOYSA-N 1,4-oxazepine-3-thione Chemical compound N=1C(COC=CC=1)=S SZCYCMXUEPXTPW-UHFFFAOYSA-N 0.000 description 1
- OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 description 1
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-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
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
- FXIWBCKGWTXJEJ-UHFFFAOYSA-N 2-chloro-n-[3-(2-chlorobenzoyl)thiophen-2-yl]acetamide Chemical compound S1C=CC(C(=O)C=2C(=CC=CC=2)Cl)=C1NC(=O)CCl FXIWBCKGWTXJEJ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- UMSGKTJDUHERQW-UHFFFAOYSA-N Brotizolam Chemical compound C1=2C=C(Br)SC=2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl UMSGKTJDUHERQW-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical compound C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical class [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 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
- 239000000376 reactant Substances 0.000 description 1
- LMHHRCOWPQNFTF-UHFFFAOYSA-N s-propan-2-yl azepane-1-carbothioate Chemical compound CC(C)SC(=O)N1CCCCCC1 LMHHRCOWPQNFTF-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752531677 DE2531677A1 (de) | 1975-07-16 | 1975-07-16 | Neue thieno-4,1-oxazepine und verfahren zu ihrer herstellung |
| DE2531678A DE2531678C3 (de) | 1975-07-16 | 1975-07-16 | Thieno [2,3e] triazole [3,4c] 5,6-dihydro-l,4diazepine und Verfahren zu ihrer Herstellung |
| DE19752531679 DE2531679A1 (de) | 1975-07-16 | 1975-07-16 | Neue thieno- eckige klammer auf 2,3-e eckige klammer zu -triazolo- eckige klammer auf 3,4-c eckige klammer zu -4,1-oxazepine und verfahren zu ihrer herstellung |
| DE2533924A DE2533924C3 (de) | 1975-07-30 | 1975-07-30 | Verfahren zur Herstellung von 6- Aryl-4H-striazolo [3,4-c] thieno [2,3-e] 1,4-diazepinen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1077475A true CA1077475A (en) | 1980-05-13 |
Family
ID=27432000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA257,092A Expired CA1077475A (en) | 1975-07-16 | 1976-07-15 | Process for production of substituted 6-aryl-4h-s-triazolo-(3,4-c)-thieno-(2,3-e)-1,4-diazepines and intermediates |
Country Status (17)
-
1976
- 1976-07-09 RO RO7686908A patent/RO76083A/ro unknown
- 1976-07-10 GR GR51234A patent/GR60819B/el unknown
- 1976-07-13 IL IL50032A patent/IL50032A/xx unknown
- 1976-07-14 CH CH901976A patent/CH627181A5/de not_active IP Right Cessation
- 1976-07-14 LU LU75384A patent/LU75384A1/xx unknown
- 1976-07-14 DD DD193857A patent/DD126744A5/xx unknown
- 1976-07-14 BG BG033745A patent/BG25227A3/xx unknown
- 1976-07-15 CA CA257,092A patent/CA1077475A/en not_active Expired
- 1976-07-15 PT PT65374A patent/PT65374B/pt unknown
- 1976-07-15 NL NLAANVRAGE7607871,A patent/NL186008C/xx not_active IP Right Cessation
- 1976-07-15 YU YU1753/76A patent/YU40458B/xx unknown
- 1976-07-15 ES ES449849A patent/ES449849A1/es not_active Expired
- 1976-07-15 AU AU15913/76A patent/AU506140B2/en not_active Expired
- 1976-07-15 MX MX761774U patent/MX4246E/es unknown
- 1976-07-16 IE IE1583/76A patent/IE43694B1/en unknown
- 1976-07-16 HU HU70CA00000291A patent/HU172620B/hu unknown
- 1976-07-16 FR FR7621836A patent/FR2318165A1/fr active Granted
-
1981
- 1981-05-19 CH CH327381A patent/CH630630A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU506140B2 (en) | 1979-12-13 |
| PT65374B (de) | 1978-06-08 |
| AU1591376A (en) | 1978-01-19 |
| HU172620B (hu) | 1978-11-28 |
| CH627181A5 (en) | 1981-12-31 |
| GR60819B (en) | 1978-08-30 |
| IL50032A (en) | 1981-03-31 |
| BG25227A3 (en) | 1978-08-10 |
| IE43694L (en) | 1977-01-16 |
| RO76083A (ro) | 1981-06-22 |
| NL7607871A (nl) | 1977-01-18 |
| DD126744A5 (enrdf_load_stackoverflow) | 1977-08-10 |
| ES449849A1 (es) | 1977-08-16 |
| CH630630A5 (en) | 1982-06-30 |
| FR2318165A1 (fr) | 1977-02-11 |
| IL50032A0 (en) | 1976-09-30 |
| FR2318165B1 (enrdf_load_stackoverflow) | 1980-02-01 |
| IE43694B1 (en) | 1981-05-06 |
| MX4246E (es) | 1982-03-02 |
| LU75384A1 (enrdf_load_stackoverflow) | 1977-07-27 |
| NL186008B (nl) | 1990-04-02 |
| NL186008C (nl) | 1990-09-03 |
| YU40458B (en) | 1986-02-28 |
| YU175376A (en) | 1982-06-30 |
| PT65374A (de) | 1976-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1076571A (en) | Tetracyclic derivatives of benzo-pyrido azepines | |
| NZ199793A (en) | Tetracyclic imidazodiazepines | |
| Klemm et al. | Chemistry of thienopyridines. III. Syntheses of the thieno [2, 3-b]-and thieno [3, 2-b] pyridine systems. Direct substitution into the former system | |
| NO146573B (no) | 3a,4-dihydro-imidazo(1,5-a)(1,4)-diazepiner som anvendes som mellomprodukter for fremstilling av terapeutisk virksomme imidazo(1,5-a)(1,4)diazepiner | |
| NO140671B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive diazepiner | |
| NO180049B (no) | Analogifremgangsmåte for fremstilling av terapeutisk aktive 9-substituerte-8-usubstituerte-9-deazaguaniner | |
| GB2169288A (en) | Tricyclic pyridine derivatives | |
| JPS6365673B2 (enrdf_load_stackoverflow) | ||
| SUGIYAMA et al. | Condensed Thienopyrimidines. II.: Synthesis and Gastric Antisecretory Activity of Thiazole and Polymethylene Condensed Thienopyrimidine Derivatives | |
| US4201712A (en) | Process for preparation of 6-aryl-4H-s-triazolo-[3,4-c]-thieno-[2,3-e]-1,4-diazepines | |
| CA1077475A (en) | Process for production of substituted 6-aryl-4h-s-triazolo-(3,4-c)-thieno-(2,3-e)-1,4-diazepines and intermediates | |
| Hirai et al. | Heterocyclic cation systems. 14. Synthesis of thieno [3, 2-e][1, 4] diazepine, thiazolo [4, 5-e][1, 4] diazepine, and s-triazolo [3, 4-c] thiazolo [4, 5-e][1, 4] diazepine derivatives | |
| Hino et al. | Agents Acting on the Central Nervous System.: Synthesis of 3-Phenyl-2-piperazinyl-1-benzazocines, 3-Substituted-2-piperazinyl-1-benzazepines and Related Compounds | |
| CA1327571C (en) | Imidazodiazepine derivatives | |
| Baba et al. | Studies on disease-modifying antirheumatic drugs. IV. Synthesis of novel thieno [2, 3-b: 5, 4-c'] dipyridine derivatives and their anti-inflammatory effect | |
| SU622406A3 (ru) | Способ получени замещенных -6-арил4н- -триазоло/3,4-с/тиено /2,3-с/-1,4диазепинов или их солей | |
| ISHIKAWA et al. | Cyclic guanidines. XIII. Synthesis of 2-amino-4-phenyl-3, 4-dihydrothieno [2, 3-d] pyrimidine derivatives | |
| Moffett | Tetracyclic heterocycles as CNS agents | |
| US3816437A (en) | Thieno(2,3-g)indazoles | |
| CA1324607C (en) | Dipyrazoles useful as bronchodilators | |
| Shafiee et al. | Selenium heterocycles XXVI. Synthesis of theino [3, 4‐b] benzofuran and selenolo [3, 4‐b] benzofuran. Two novel heterocycles | |
| NZ201506A (en) | 8-(halo or nitro)-6-(phenyl or pyrid-2-yl)-4h-s-triazolo(4,3-a)(1)benzazepines | |
| Wynberg et al. | Heterohelicenes containing seven-membered rings. 5, 6-Dihydro-4H-dithien [2, 3-c: 3', 2'e] azepines | |
| KR800000557B1 (ko) | 치환된 6-아릴-4H-S-트리아졸로-[3, 4-C]-티에노-[2, 3-e]-1, 4-디아제핀의 제조방법 | |
| US3201396A (en) | Novel 4, 5-polymethylene-(6h)-1, 2, 6-thiadiazine-1, 1-dioxides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |