AT391696B - Verfahren zur herstellung von s- 3morpholino-4- (3'-tert-butylamino-2'-hydroxypropoxy)-1,2,5thiadiazol - Google Patents

Verfahren zur herstellung von s- 3morpholino-4- (3'-tert-butylamino-2'-hydroxypropoxy)-1,2,5thiadiazol Download PDF

Info

Publication number: AT391696B
Authority: AT; Austria
Prior art keywords: thiadiazole; timolol; tert; formula; morpholino
Prior art date: 1984-03-30

Application number

AT0087685A

Other languages

German (de)

English (en)

Other versions

ATA87685A (de

Original Assignee

Star Oy Ab

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.)

1984-03-30

Filing date

1985-03-25

Publication date

1990-11-12

1985-03-25 Application filed by Star Oy Ab filed Critical Star Oy Ab

1990-05-15 Publication of ATA87685A publication Critical patent/ATA87685A/de

1990-11-12 Application granted granted Critical

1990-11-12 Publication of AT391696B publication Critical patent/AT391696B/de

Links

238000004519 manufacturing process Methods 0.000 title description 6
239000000203 mixture Substances 0.000 claims description 35
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
238000000034 method Methods 0.000 claims description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
238000002360 preparation method Methods 0.000 claims description 20
239000000243 solution Substances 0.000 claims description 20
230000003287 optical effect Effects 0.000 claims description 19
238000000354 decomposition reaction Methods 0.000 claims description 17
238000004128 high performance liquid chromatography Methods 0.000 claims description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
-1 hydroxypropoxy Chemical group 0.000 claims description 11
BLJRIMJGRPQVNF-SNVBAGLBSA-N (R)-timolol Chemical compound CC(C)(C)NC[C@@H](O)COC1=NSN=C1N1CCOCC1 BLJRIMJGRPQVNF-SNVBAGLBSA-N 0.000 claims description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
238000010992 reflux Methods 0.000 claims description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
238000002425 crystallisation Methods 0.000 claims description 8
230000008025 crystallization Effects 0.000 claims description 8
FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 claims description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
238000001914 filtration Methods 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
150000001875 compounds Chemical class 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 4
239000007864 aqueous solution Substances 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
229910004373 HOAc Inorganic materials 0.000 claims description 3
238000005903 acid hydrolysis reaction Methods 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
239000005457 ice water Substances 0.000 claims description 3
UIKHKLFBHLPAPO-HTQZYQBOSA-N (2r,3r)-2,3-diacetyl-2,3-dihydroxybutanedioic acid Chemical compound CC(=O)[C@@](O)(C(O)=O)[C@@](O)(C(C)=O)C(O)=O UIKHKLFBHLPAPO-HTQZYQBOSA-N 0.000 claims description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
239000011976 maleic acid Substances 0.000 claims description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
125000001589 carboacyl group Chemical group 0.000 claims 1
239000001257 hydrogen Substances 0.000 claims 1
229960004605 timolol Drugs 0.000 description 50
239000002585 base Substances 0.000 description 20
239000000047 product Substances 0.000 description 19
150000003839 salts Chemical class 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
239000007858 starting material Substances 0.000 description 11
TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
DWUZILHYAJBUBR-UHFFFAOYSA-N 4-morpholin-4-yl-1,2,5-thiadiazol-3-one Chemical compound OC1=NSN=C1N1CCOCC1 DWUZILHYAJBUBR-UHFFFAOYSA-N 0.000 description 8
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
SULAQIPCRIBAKU-UHFFFAOYSA-N 1-tert-butylazetidin-3-ol;hydrochloride Chemical compound Cl.CC(C)(C)N1CC(O)C1 SULAQIPCRIBAKU-UHFFFAOYSA-N 0.000 description 3
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000003643 water by type Substances 0.000 description 3
KGCYYMUHGZTDQN-YUMQZZPRSA-N (3S,4S)-3,4-diacetyl-3,4-dihydroxyoxolane-2,5-dione Chemical compound C(C)(=O)[C@]1([C@](C(=O)OC1=O)(O)C(C)=O)O KGCYYMUHGZTDQN-YUMQZZPRSA-N 0.000 description 2
DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 2
MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-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
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
229960001270 d- tartaric acid Drugs 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000012634 fragment Substances 0.000 description 2
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical group OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
150000002924 oxiranes Chemical class 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
BOGVTNYNTGOONP-JCYAYHJZSA-N (3R,4R)-3,4-dihydroxyoxolane-2,5-dione Chemical class O[C@@H]1[C@@H](O)C(=O)OC1=O BOGVTNYNTGOONP-JCYAYHJZSA-N 0.000 description 1
MUHCEAIVGKVBHE-UHFFFAOYSA-N 1,2,5-thiadiazol-3-one Chemical class OC=1C=NSN=1 MUHCEAIVGKVBHE-UHFFFAOYSA-N 0.000 description 1
150000004868 1,2,5-thiadiazoles Chemical class 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
ZQQSYPZAPHRXRY-UHFFFAOYSA-N 1-hydroxyazetidine Chemical compound ON1CCC1 ZQQSYPZAPHRXRY-UHFFFAOYSA-N 0.000 description 1
WABVFCKCUCWPLZ-UHFFFAOYSA-N 4-(1,2,5-thiadiazol-3-yl)morpholin-3-ol Chemical compound OC1COCCN1C1=NSN=C1 WABVFCKCUCWPLZ-UHFFFAOYSA-N 0.000 description 1
LAUCCQWGVCJGFT-UHFFFAOYSA-N 4-(4-chloro-1,2,5-thiadiazol-3-yl)morpholine Chemical compound ClC1=NSN=C1N1CCOCC1 LAUCCQWGVCJGFT-UHFFFAOYSA-N 0.000 description 1
BHBZGQBBRQJXCY-UHFFFAOYSA-N 4-chloro-1,2,5-thiadiazol-3-one Chemical compound OC1=NSN=C1Cl BHBZGQBBRQJXCY-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
101100063251 Bacillus subtilis (strain 168) desR gene Proteins 0.000 description 1
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
IWYRWIUNAVNFPE-UHFFFAOYSA-N Glycidaldehyde Chemical compound O=CC1CO1 IWYRWIUNAVNFPE-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
239000002262 Schiff base Substances 0.000 description 1
150000004753 Schiff bases Chemical class 0.000 description 1
XAKITKDHDMPGPW-WDSKDSINSA-N [(3s,4s)-4-acetyloxy-2,5-dioxooxolan-3-yl] acetate Chemical compound CC(=O)O[C@H]1[C@H](OC(C)=O)C(=O)OC1=O XAKITKDHDMPGPW-WDSKDSINSA-N 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical group C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 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
229910052799 carbon Inorganic materials 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
238000004821 distillation Methods 0.000 description 1
PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000009776 industrial production Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
150000002917 oxazolidines Chemical class 0.000 description 1
230000008447 perception Effects 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
239000001294 propane Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000006340 racemization Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical group CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
BLJRIMJGRPQVNF-UHFFFAOYSA-N timolol Chemical compound CC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC1 BLJRIMJGRPQVNF-UHFFFAOYSA-N 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 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
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

AT0087685A 1984-03-30 1985-03-25 Verfahren zur herstellung von s- 3morpholino-4- (3'-tert-butylamino-2'-hydroxypropoxy)-1,2,5thiadiazol AT391696B (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FI841292A FI71933C (fi)	1984-03-30	1984-03-30	Nya l-vinsyra-0-monoestrar av 3-morfolino-4-(3'-tert.-butylamino-2'-hydroxipropoxi)-1,2,5-tiadiazol och deras anvaendning saosom mellanprodukter.

Publications (2)

Publication Number	Publication Date
ATA87685A ATA87685A (de)	1990-05-15
AT391696B true AT391696B (de)	1990-11-12

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ID=8518831

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Application Number	Title	Priority Date	Filing Date
AT0087685A AT391696B (de)	1984-03-30	1985-03-25	Verfahren zur herstellung von s- 3morpholino-4- (3'-tert-butylamino-2'-hydroxypropoxy)-1,2,5thiadiazol

Country Status (9)

Country	Link
AT (1)	AT391696B (da)
CH (1)	CH663208A5 (da)
DD (1)	DD234011A5 (da)
DK (1)	DK162283C (da)
FI (1)	FI71933C (da)
NL (1)	NL192386C (da)
NO (1)	NO158020C (da)
SE (1)	SE463101B (da)
SU (1)	SU1417798A3 (da)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0440684B1 (en) *	1988-10-20	1994-09-28	Leiras Oy	Novel s-timolol derivative and process for its preparation

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0305496A4 (en) *	1987-03-17	1989-07-11	Insite Vision Inc	TIMOLOL DERIVATIVES.

1984
- 1984-03-30 FI FI841292A patent/FI71933C/fi not_active IP Right Cessation
1985
- 1985-03-25 AT AT0087685A patent/AT391696B/de not_active IP Right Cessation
- 1985-03-28 DD DD85274555A patent/DD234011A5/de not_active IP Right Cessation
- 1985-03-28 SE SE8501540A patent/SE463101B/sv not_active IP Right Cessation
- 1985-03-29 NO NO851307A patent/NO158020C/no unknown
- 1985-03-29 DK DK142885A patent/DK162283C/da active
- 1985-03-29 SU SU853873552A patent/SU1417798A3/ru active
- 1985-03-29 NL NL8500939A patent/NL192386C/nl not_active IP Right Cessation
- 1985-04-01 CH CH1412/85A patent/CH663208A5/de not_active IP Right Cessation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0440684B1 (en) *	1988-10-20	1994-09-28	Leiras Oy	Novel s-timolol derivative and process for its preparation

Also Published As

Publication number	Publication date
NO158020B (no)	1988-03-21
DK142885A (da)	1985-10-01
FI841292A7 (fi)	1985-10-01
FI71933C (fi)	1989-04-06
CH663208A5 (en)	1987-11-30
FI841292A0 (fi)	1984-03-30
DK162283B (da)	1991-10-07
SE8501540L (sv)	1985-10-01
ATA87685A (de)	1990-05-15
DD234011A5 (de)	1986-03-19
NL8500939A (nl)	1985-10-16
DK162283C (da)	1992-03-02
FI71933B (fi)	1986-11-28
NO158020C (no)	1990-05-02
SE463101B (sv)	1990-10-08
NL192386B (nl)	1997-03-03
NO851307L (no)	1985-10-01
DK142885D0 (da)	1985-03-29
SE8501540D0 (sv)	1985-03-28
NL192386C (nl)	1997-07-04
SU1417798A3 (ru)	1988-08-15

Legal Events

Date	Code	Title	Description
1999-01-15	ELJ	Ceased due to non-payment of the annual fee
2000-11-15	REN	Ceased due to non-payment of the annual fee

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AT391696B - Verfahren zur herstellung von s- 3morpholino-4- (3'-tert-butylamino-2'-hydroxypropoxy)-1,2,5thiadiazol - Google Patents

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Applications Claiming Priority (1)

Publications (2)

Family

ID=8518831

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Country Status (9)

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