SE463101B - L-vinsyra-o-monoestrar av 3-morfolino-4-(3'-tert-butylamino-2'-hydroxipropoxi)-1,2,5-tiadiazol, foerfarande foer framstaellning daerav samt deras anvaendning som mellanprodukter vid framstaellning av s-3-morfolino-4-(3'-tert-butylamino-2'hydroxipropoxi)-1,2,5-tiadiazol - Google Patents
L-vinsyra-o-monoestrar av 3-morfolino-4-(3'-tert-butylamino-2'-hydroxipropoxi)-1,2,5-tiadiazol, foerfarande foer framstaellning daerav samt deras anvaendning som mellanprodukter vid framstaellning av s-3-morfolino-4-(3'-tert-butylamino-2'hydroxipropoxi)-1,2,5-tiadiazolInfo
- Publication number
- SE463101B SE463101B SE8501540A SE8501540A SE463101B SE 463101 B SE463101 B SE 463101B SE 8501540 A SE8501540 A SE 8501540A SE 8501540 A SE8501540 A SE 8501540A SE 463101 B SE463101 B SE 463101B
- Authority
- SE
- Sweden
- Prior art keywords
- morpholino
- tert
- formula
- thiadiazole
- butylamino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 26
- 238000002360 preparation method Methods 0.000 title claims description 20
- BLJRIMJGRPQVNF-UHFFFAOYSA-N timolol Chemical compound CC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC1 BLJRIMJGRPQVNF-UHFFFAOYSA-N 0.000 title claims description 3
- 239000002253 acid Substances 0.000 title description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- -1 p-methylbenzoyl Chemical group 0.000 claims description 13
- 238000002425 crystallisation Methods 0.000 claims description 11
- 230000008025 crystallization Effects 0.000 claims description 11
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 3
- 229960004605 timolol Drugs 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 22
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- 239000000203 mixture Substances 0.000 description 19
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- 238000004128 high performance liquid chromatography Methods 0.000 description 16
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 11
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- 238000003756 stirring Methods 0.000 description 10
- BLJRIMJGRPQVNF-SNVBAGLBSA-N (R)-timolol Chemical compound CC(C)(C)NC[C@@H](O)COC1=NSN=C1N1CCOCC1 BLJRIMJGRPQVNF-SNVBAGLBSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
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- 238000010992 reflux Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
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- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 5
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- 238000005481 NMR spectroscopy Methods 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
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- 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 3
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 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
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
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- 239000005457 ice water Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 239000003643 water by type Substances 0.000 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 description 2
- 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
- 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 description 2
- 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 2
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- 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
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 2
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- 238000001819 mass spectrum Methods 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
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- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 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
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 235000015067 sauces Nutrition 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
- HEMHJVSKTPXQMS-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-N 0.000 description 1
- 238000004677 spark ionization mass spectrometry Methods 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
- 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
- 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)
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 (3)
| Publication Number | Publication Date |
|---|---|
| SE8501540D0 SE8501540D0 (sv) | 1985-03-28 |
| SE8501540L SE8501540L (sv) | 1985-10-01 |
| SE463101B true SE463101B (sv) | 1990-10-08 |
Family
ID=8518831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8501540A SE463101B (sv) | 1984-03-30 | 1985-03-28 | L-vinsyra-o-monoestrar av 3-morfolino-4-(3'-tert-butylamino-2'-hydroxipropoxi)-1,2,5-tiadiazol, foerfarande foer framstaellning daerav samt deras anvaendning som mellanprodukter vid framstaellning av s-3-morfolino-4-(3'-tert-butylamino-2'hydroxipropoxi)-1,2,5-tiadiazol |
Country Status (9)
| Country | Link |
|---|---|
| AT (1) | AT391696B (de) |
| CH (1) | CH663208A5 (de) |
| DD (1) | DD234011A5 (de) |
| DK (1) | DK162283C (de) |
| FI (1) | FI71933C (de) |
| NL (1) | NL192386C (de) |
| NO (1) | NO158020C (de) |
| SE (1) | SE463101B (de) |
| SU (1) | SU1417798A3 (de) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0305496A4 (de) * | 1987-03-17 | 1989-07-11 | Insite Vision Inc | Timolol-derivate. |
| FI82240C (fi) * | 1988-10-20 | 1991-02-11 | Huhtamaeki Oy | Foerfarande foer framstaellning av farmakologiskt vaerdefullt s-timolol-hemihydrat. |
-
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 SE SE8501540A patent/SE463101B/sv not_active IP Right Cessation
- 1985-03-28 DD DD85274555A patent/DD234011A5/de not_active IP Right Cessation
- 1985-03-29 NO NO851307A patent/NO158020C/no unknown
- 1985-03-29 SU SU853873552A patent/SU1417798A3/ru active
- 1985-03-29 NL NL8500939A patent/NL192386C/nl not_active IP Right Cessation
- 1985-03-29 DK DK142885A patent/DK162283C/da active
- 1985-04-01 CH CH1412/85A patent/CH663208A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE8501540L (sv) | 1985-10-01 |
| DK162283C (da) | 1992-03-02 |
| NO158020B (no) | 1988-03-21 |
| NO158020C (no) | 1990-05-02 |
| DK142885A (da) | 1985-10-01 |
| FI841292A7 (fi) | 1985-10-01 |
| DK162283B (da) | 1991-10-07 |
| NL192386B (nl) | 1997-03-03 |
| FI71933B (fi) | 1986-11-28 |
| NL8500939A (nl) | 1985-10-16 |
| DD234011A5 (de) | 1986-03-19 |
| FI71933C (fi) | 1989-04-06 |
| CH663208A5 (en) | 1987-11-30 |
| SU1417798A3 (ru) | 1988-08-15 |
| FI841292A0 (fi) | 1984-03-30 |
| AT391696B (de) | 1990-11-12 |
| NO851307L (no) | 1985-10-01 |
| NL192386C (nl) | 1997-07-04 |
| ATA87685A (de) | 1990-05-15 |
| DK142885D0 (da) | 1985-03-29 |
| SE8501540D0 (sv) | 1985-03-28 |
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