JPH0376307B2 - - Google Patents
Info
- Publication number
- JPH0376307B2 JPH0376307B2 JP3254790A JP3254790A JPH0376307B2 JP H0376307 B2 JPH0376307 B2 JP H0376307B2 JP 3254790 A JP3254790 A JP 3254790A JP 3254790 A JP3254790 A JP 3254790A JP H0376307 B2 JPH0376307 B2 JP H0376307B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- mixture
- methoxyphenyl
- hydroxy
- solvent
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- KJFRSZASZNLCDF-UHFFFAOYSA-N 1,5-benzothiazepine Chemical class S1C=CC=NC2=CC=CC=C12 KJFRSZASZNLCDF-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- 239000000203 mixture Substances 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 48
- -1 propylthio group Chemical group 0.000 description 43
- 150000001875 compounds Chemical class 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000013078 crystal Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000000284 extract Substances 0.000 description 7
- 239000012452 mother liquor Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- WCQRVIOIOCNIFM-UHFFFAOYSA-N 1,2-benzothiazepin-3-one Chemical class C1=CC(=O)NSC2=CC=CC=C21 WCQRVIOIOCNIFM-UHFFFAOYSA-N 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 235000019260 propionic acid Nutrition 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- LLDKXUJEKINCIS-CVEARBPZSA-N (2s,3s)-3-hydroxy-7-methoxy-2-(4-methoxyphenyl)-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC(OC)=CC=C2S1 LLDKXUJEKINCIS-CVEARBPZSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000007657 benzothiazepines Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- YKNYRRVISWJDSR-UHFFFAOYSA-N methyl oxirane-2-carboxylate Chemical compound COC(=O)C1CO1 YKNYRRVISWJDSR-UHFFFAOYSA-N 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical class 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 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- IJUJSPFBPXPAOB-CVEARBPZSA-N (2s,3s)-3-hydroxy-2-(4-methoxyphenyl)-8-methylsulfanyl-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC=C(SC)C=C2S1 IJUJSPFBPXPAOB-CVEARBPZSA-N 0.000 description 2
- DDCMSFIMXFOYFK-CVEARBPZSA-N (2s,3s)-3-hydroxy-8-methoxy-2-(4-methoxyphenyl)-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC=C(OC)C=C2S1 DDCMSFIMXFOYFK-CVEARBPZSA-N 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VUMZNLOQJGKGNE-UHFFFAOYSA-N 2-amino-5-methylbenzenethiol Chemical compound CC1=CC=C(N)C(S)=C1 VUMZNLOQJGKGNE-UHFFFAOYSA-N 0.000 description 2
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- ARQVRCKIVSELCG-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(OC)C=C1 ARQVRCKIVSELCG-UHFFFAOYSA-N 0.000 description 2
- AKQLYAFBUYHFCK-UHFFFAOYSA-N methyl 4-methoxybenzenepropanoate Natural products COC(=O)CCC1=CC=C(OC)C=C1 AKQLYAFBUYHFCK-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003151 propanoic acid esters Chemical class 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000001119 stannous chloride Substances 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- JHVKQEXNQYGGOH-AWEZNQCLSA-N (2s)-1-naphthalen-2-ylsulfonylpyrrolidine-2-carbonyl chloride Chemical compound ClC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 JHVKQEXNQYGGOH-AWEZNQCLSA-N 0.000 description 1
- LLDKXUJEKINCIS-HOTGVXAUSA-N (2s,3r)-3-hydroxy-7-methoxy-2-(4-methoxyphenyl)-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@H](O)C(=O)NC2=CC(OC)=CC=C2S1 LLDKXUJEKINCIS-HOTGVXAUSA-N 0.000 description 1
- AMEWDAJHPHGXHU-CVEARBPZSA-N (2s,3s)-3-hydroxy-2-(4-methoxyphenyl)-6-methyl-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=C(C)C=CC=C2S1 AMEWDAJHPHGXHU-CVEARBPZSA-N 0.000 description 1
- CFHSRRHWFWQPBI-CVEARBPZSA-N (2s,3s)-3-hydroxy-2-(4-methoxyphenyl)-7-methylsulfanyl-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC(SC)=CC=C2S1 CFHSRRHWFWQPBI-CVEARBPZSA-N 0.000 description 1
- WMRVVEOKIZNPPZ-CVEARBPZSA-N (2s,3s)-3-hydroxy-2-(4-methoxyphenyl)-8-methyl-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC=C(C)C=C2S1 WMRVVEOKIZNPPZ-CVEARBPZSA-N 0.000 description 1
- PXXASJOVZFQJMH-CVEARBPZSA-N (2s,3s)-3-hydroxy-8-methyl-2-(4-methylphenyl)-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(C)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC=C(C)C=C2S1 PXXASJOVZFQJMH-CVEARBPZSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- HZONRRHNQILCNO-UHFFFAOYSA-N 1-methyl-2h-pyridine Chemical compound CN1CC=CC=C1 HZONRRHNQILCNO-UHFFFAOYSA-N 0.000 description 1
- JHVKQEXNQYGGOH-UHFFFAOYSA-N 1-naphthalen-2-ylsulfonylpyrrolidine-2-carbonyl chloride Chemical compound ClC(=O)C1CCCN1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 JHVKQEXNQYGGOH-UHFFFAOYSA-N 0.000 description 1
- MHKRINONGZJSSL-UHFFFAOYSA-N 2,4-dinitrobenzenethiol Chemical compound [O-][N+](=O)C1=CC=C(S)C([N+]([O-])=O)=C1 MHKRINONGZJSSL-UHFFFAOYSA-N 0.000 description 1
- MVTRQRSNYWDWMY-UHFFFAOYSA-N 2-amino-4-(trifluoromethyl)benzenethiol Chemical compound NC1=CC(C(F)(F)F)=CC=C1S MVTRQRSNYWDWMY-UHFFFAOYSA-N 0.000 description 1
- KIDLBEYNOGVICH-UHFFFAOYSA-N 2-amino-4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C(N)=C1 KIDLBEYNOGVICH-UHFFFAOYSA-N 0.000 description 1
- QCLMTLDABHUUBC-UHFFFAOYSA-N 2-amino-4-methylbenzenethiol Chemical compound CC1=CC=C(S)C(N)=C1 QCLMTLDABHUUBC-UHFFFAOYSA-N 0.000 description 1
- MEYBCGKCAAFWQG-UHFFFAOYSA-N 2-amino-4-methylsulfanylbenzenethiol Chemical compound CSC1=CC=C(S)C(N)=C1 MEYBCGKCAAFWQG-UHFFFAOYSA-N 0.000 description 1
- BTOIUVBIVLOTIU-UHFFFAOYSA-N 2-amino-5-methylsulfanylbenzenethiol Chemical compound CSC1=CC=C(N)C(S)=C1 BTOIUVBIVLOTIU-UHFFFAOYSA-N 0.000 description 1
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- GFHZCXYRWLBACS-UHFFFAOYSA-N 5H-1,5-benzothiazepin-4-one hydrobromide Chemical compound Br.S1C=CC(NC2=C1C=CC=C2)=O GFHZCXYRWLBACS-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- UGYYKNIFLAJPAS-UHFFFAOYSA-N 8-methoxy-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound N1C(=O)CCSC2=CC(OC)=CC=C21 UGYYKNIFLAJPAS-UHFFFAOYSA-N 0.000 description 1
- ZYUZLEUJKZZXNN-UHFFFAOYSA-N C1=CC(CC(N)C(O)=O)=CC=C1OS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 Chemical group C1=CC(CC(N)C(O)=O)=CC=C1OS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 ZYUZLEUJKZZXNN-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- PKQMMSMEARUAFI-NSLUPJTDSA-N [(2s,3s)-5-[2-(dimethylamino)ethyl]-8-methoxy-2-(4-methylphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@H]2[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C3=CC=C(C=C3S2)OC)=CC=C(C)C=C1 PKQMMSMEARUAFI-NSLUPJTDSA-N 0.000 description 1
- HFPIIQJEGNRCES-MSOLQXFVSA-N [(2s,3s)-8-methoxy-2-(4-methoxyphenyl)-4-oxo-3,5-dihydro-2h-1,5-benzothiazepin-3-yl] acetate Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)NC2=CC=C(OC)C=C2S1 HFPIIQJEGNRCES-MSOLQXFVSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- BICAGYDGRXJYGD-UHFFFAOYSA-N hydrobromide;hydrochloride Chemical compound Cl.Br BICAGYDGRXJYGD-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- QRNDDJXJUHBGSG-UHFFFAOYSA-N methoxyethyne Chemical group COC#C QRNDDJXJUHBGSG-UHFFFAOYSA-N 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical class COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- VSWLXYAZJZQIKA-UHFFFAOYSA-N tetrachloromethane;triphenylphosphane Chemical compound ClC(Cl)(Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VSWLXYAZJZQIKA-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848406318A GB8406318D0 (en) | 1984-03-10 | 1984-03-10 | 1 5-benzothiazepine derivatives |
| GB8406318 | 1984-03-10 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4423985A Division JPH0228594B2 (ja) | 1984-03-10 | 1985-03-05 | 1*55benzochiazepinjudotai |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02288871A JPH02288871A (ja) | 1990-11-28 |
| JPH0376307B2 true JPH0376307B2 (es) | 1991-12-05 |
Family
ID=10557882
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4423985A Expired - Lifetime JPH0228594B2 (ja) | 1984-03-10 | 1985-03-05 | 1*55benzochiazepinjudotai |
| JP3254790A Granted JPH02288871A (ja) | 1984-03-10 | 1990-02-15 | １，５‐ベンゾチアゼピン誘導体 |
| JP3254690A Granted JPH02288828A (ja) | 1984-03-10 | 1990-02-15 | 医薬組成物 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4423985A Expired - Lifetime JPH0228594B2 (ja) | 1984-03-10 | 1985-03-05 | 1*55benzochiazepinjudotai |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3254690A Granted JPH02288828A (ja) | 1984-03-10 | 1990-02-15 | 医薬組成物 |
Country Status (2)
| Country | Link |
|---|---|
| JP (3) | JPH0228594B2 (es) |
| GB (1) | GB8406318D0 (es) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS649981A (en) * | 1987-06-29 | 1989-01-13 | Tanabe Seiyaku Co | 1,5-benzothiazepine derivative |
| JPS649982A (en) * | 1987-06-30 | 1989-01-13 | Tanabe Seiyaku Co | 1,5-benzothiazepine derivative |
| JP2703564B2 (ja) * | 1987-07-31 | 1998-01-26 | 田辺製薬株式会社 | １，５−ベンゾチアゼピン誘導体 |
| JPS6445376A (en) * | 1987-08-12 | 1989-02-17 | Tanabe Seiyaku Co | Production of 1,5-benzothiazepine derivative |
| JPS6450872A (en) * | 1987-08-21 | 1989-02-27 | Tanabe Seiyaku Co | Production of 1,5-benzothiazepine derivative |
| JPH01128974A (ja) * | 1987-11-13 | 1989-05-22 | Tanabe Seiyaku Co Ltd | １，５−ベンゾチアゼピン誘導体の製法 |
| JP2863534B2 (ja) * | 1988-10-24 | 1999-03-03 | マリオン ラボラトリーズ，インコーポレイティド | 医薬組成物 |
| FR2641535B1 (fr) * | 1989-01-11 | 1991-03-15 | Synthelabo | Procede de preparation de (+) - (2s, 3s)-hydroxy-3 (methoxy-4 phenyl)-2 dihydro-2,3 5h-benzothiazepine-1,5 one-4 |
| JPH0699409B2 (ja) * | 1989-04-28 | 1994-12-07 | 田辺製薬株式会社 | １，５―ベンゾチアゼピン誘導体の製法 |
| JP2674232B2 (ja) * | 1989-08-31 | 1997-11-12 | 田辺製薬株式会社 | １，５―ベンゾチアゼピン誘導体 |
| JPH0779706B2 (ja) * | 1990-03-22 | 1995-08-30 | 田辺製薬株式会社 | ２―クロロ―３―ヒドロキシ―３―フエニルプロピオン酸エステル類の製法 |
| JPH078799B2 (ja) * | 1990-09-17 | 1995-02-01 | 田辺製薬株式会社 | 血小板凝集抑制組成物 |
| JPH078798B2 (ja) * | 1990-09-17 | 1995-02-01 | 田辺製薬株式会社 | 血小板凝集抑制組成物 |
| JP2643798B2 (ja) * | 1992-10-23 | 1997-08-20 | 田辺製薬株式会社 | 末梢動脈血流増加剤 |
| IL123352A0 (en) * | 1997-02-27 | 1998-09-24 | Tanabe Seiyaku Co | Process for preparing an optically active trans-3-substituted glycidic acid ester |
-
1984
- 1984-03-10 GB GB848406318A patent/GB8406318D0/en active Pending
-
1985
- 1985-03-05 JP JP4423985A patent/JPH0228594B2/ja not_active Expired - Lifetime
-
1990
- 1990-02-15 JP JP3254790A patent/JPH02288871A/ja active Granted
- 1990-02-15 JP JP3254690A patent/JPH02288828A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02288828A (ja) | 1990-11-28 |
| JPS60202871A (ja) | 1985-10-14 |
| JPH02288871A (ja) | 1990-11-28 |
| GB8406318D0 (en) | 1984-04-11 |
| JPH0427213B2 (es) | 1992-05-11 |
| JPH0228594B2 (ja) | 1990-06-25 |
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| Date | Code | Title | Description |
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| R250 | Receipt of annual fees |
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| EXPY | Cancellation because of completion of term |