CH471064A - Verfahren zur Herstellung von Estern von a-Alkylthyroninderivaten - Google Patents
Verfahren zur Herstellung von Estern von a-AlkylthyroninderivatenInfo
- Publication number
- CH471064A CH471064A CH1433666A CH1433666A CH471064A CH 471064 A CH471064 A CH 471064A CH 1433666 A CH1433666 A CH 1433666A CH 1433666 A CH1433666 A CH 1433666A CH 471064 A CH471064 A CH 471064A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- compounds
- yield
- theory
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- 230000008569 process Effects 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 5
- 150000002148 esters Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 238000010533 azeotropic distillation Methods 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- 238000002844 melting Methods 0.000 description 37
- 230000008018 melting Effects 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 12
- 241000700159 Rattus Species 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 229940091173 hydantoin Drugs 0.000 description 9
- 229940034208 thyroxine Drugs 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- MQBNQPWBYRKFKN-INIZCTEOSA-N (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]-2-methylpropanoic acid Chemical compound IC=1C=C(C[C@](N)(C(=O)O)C)C=C(C=1OC1=CC(=C(C=C1)O)I)I MQBNQPWBYRKFKN-INIZCTEOSA-N 0.000 description 5
- OCAZOCCWHWCEPV-KRWDZBQOSA-N (2s)-2-formamido-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]-2-methylpropanoic acid Chemical compound IC1=CC(C[C@](C)(NC=O)C(O)=O)=CC(I)=C1OC1=CC=C(O)C=C1 OCAZOCCWHWCEPV-KRWDZBQOSA-N 0.000 description 5
- -1 benzyl ester Chemical class 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 5
- 230000037323 metabolic rate Effects 0.000 description 5
- HUSVOOUYGVGJGG-INIZCTEOSA-N (2s)-2-amino-3-[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]-2-methylpropanoic acid Chemical compound IC1=CC(C[C@@](N)(C)C(O)=O)=CC(I)=C1OC1=CC=C(O)C=C1 HUSVOOUYGVGJGG-INIZCTEOSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- CQRBELJPAZUIIW-KRWDZBQOSA-N (2S)-2-amino-2-[[4-(4-hydroxyphenoxy)-3,5-diiodophenyl]methyl]butanoic acid Chemical compound C(C)[C@](N)(CC1=CC(=C(C(=C1)I)OC1=CC=C(C=C1)O)I)C(=O)O CQRBELJPAZUIIW-KRWDZBQOSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- HRNSODLWWQUGEP-AWEZNQCLSA-N IC1=CC(C[C@H](NCC)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 Chemical compound IC1=CC(C[C@H](NCC)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 HRNSODLWWQUGEP-AWEZNQCLSA-N 0.000 description 3
- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229950008325 levothyroxine Drugs 0.000 description 3
- 230000036284 oxygen consumption Effects 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- RBYSDQUOOAMRFY-KRWDZBQOSA-N (2S)-2-amino-2-[[4-(4-hydroxyphenoxy)-3-iodophenyl]methyl]butanoic acid Chemical compound C(C)[C@](N)(CC1=CC(=C(C=C1)OC1=CC=C(C=C1)O)I)C(=O)O RBYSDQUOOAMRFY-KRWDZBQOSA-N 0.000 description 2
- DXBXFNKWRXAJIA-HNNXBMFYSA-N (2s)-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-2-(propylamino)propanoic acid Chemical compound IC1=CC(C[C@H](NCCC)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 DXBXFNKWRXAJIA-HNNXBMFYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical class [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000005495 thyroid hormone Substances 0.000 description 2
- 229940036555 thyroid hormone Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 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
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KKCIOUWDFWQUBT-AWEZNQCLSA-N L-thyronine Chemical class C1=CC(C[C@H](N)C(O)=O)=CC=C1OC1=CC=C(O)C=C1 KKCIOUWDFWQUBT-AWEZNQCLSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000651 anti-goitrogenic effect Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- VVDGWALACJEJKG-UHFFFAOYSA-N iodamide Chemical compound CC(=O)NCC1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I VVDGWALACJEJKG-UHFFFAOYSA-N 0.000 description 1
- 229960004901 iodamide Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 229950000329 thiouracil Drugs 0.000 description 1
- 230000000929 thyromimetic effect Effects 0.000 description 1
- 230000001897 thyrotoxic effect Effects 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH108369A CH477405A (de) | 1965-10-07 | 1966-10-05 | Verfahren zur Herstellung von Estern von a-Alkylthyroninderivaten |
| CH108569A CH491088A (de) | 1965-10-07 | 1966-10-05 | Verfahren zur Herstellung von Estern von a-Alkyl-thyroninderivaten |
| CH108269A CH471079A (de) | 1965-10-07 | 1966-10-05 | Verfahren zur Herstellung von Estern von a-Alkylthyroninderivaten |
| CH108469A CH490336A (de) | 1965-10-07 | 1966-10-05 | Verfahren zur Herstellung von Estern von a-Alkyl-thyroninderivaten |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC0037070 | 1965-10-07 | ||
| DE19651493567 DE1493567C3 (de) | 1965-10-07 | 1965-10-07 | Ester von alpha-Alkylthyroxinderivaten und Verfahren zu ihrer Herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH471064A true CH471064A (de) | 1969-04-15 |
Family
ID=31947311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1433666A CH471064A (de) | 1965-10-07 | 1966-10-05 | Verfahren zur Herstellung von Estern von a-Alkylthyroninderivaten |
Country Status (15)
| Country | Link |
|---|---|
| AT (5) | AT275750B (en)) |
| BE (1) | BE687980A (en)) |
| BR (1) | BR6683492D0 (en)) |
| CH (1) | CH471064A (en)) |
| DK (1) | DK127383B (en)) |
| FI (1) | FI45188C (en)) |
| FR (1) | FR1496285A (en)) |
| GB (1) | GB1112874A (en)) |
| IL (1) | IL26568A (en)) |
| NL (1) | NL147133B (en)) |
| NO (1) | NO119317B (en)) |
| OA (1) | OA02150A (en)) |
| SE (1) | SE345259B (en)) |
| SU (1) | SU374817A3 (en)) |
| YU (1) | YU34028B (en)) |
-
1966
- 1966-09-22 FI FI662493A patent/FI45188C/fi active
- 1966-09-23 IL IL26568A patent/IL26568A/xx unknown
- 1966-09-26 AT AT108968A patent/AT275750B/de active
- 1966-09-26 AT AT01113/68A patent/AT277481B/de active
- 1966-09-26 AT AT901566A patent/AT270090B/de active
- 1966-09-26 AT AT01111/68A patent/AT282081B/de active
- 1966-09-29 GB GB43633/66A patent/GB1112874A/en not_active Expired
- 1966-10-03 YU YU1863/66A patent/YU34028B/xx unknown
- 1966-10-04 OA OA52616A patent/OA02150A/xx unknown
- 1966-10-05 SU SU1105855A patent/SU374817A3/ru active
- 1966-10-05 CH CH1433666A patent/CH471064A/de not_active IP Right Cessation
- 1966-10-05 NO NO165017A patent/NO119317B/no unknown
- 1966-10-06 DK DK518966AA patent/DK127383B/da unknown
- 1966-10-06 SE SE13497/66A patent/SE345259B/xx unknown
- 1966-10-07 BR BR183492/66A patent/BR6683492D0/pt unknown
- 1966-10-07 NL NL666614150A patent/NL147133B/xx unknown
- 1966-10-07 FR FR79226A patent/FR1496285A/fr not_active Expired
- 1966-10-07 BE BE687980D patent/BE687980A/xx unknown
-
1968
- 1968-09-26 AT AT111268A patent/AT287927B/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE345259B (en)) | 1972-05-23 |
| IL26568A (en) | 1971-02-25 |
| NL6614150A (en)) | 1967-04-10 |
| NL147133B (nl) | 1975-09-15 |
| GB1112874A (en) | 1968-05-08 |
| AT282081B (de) | 1970-06-10 |
| FI45188B (en)) | 1971-12-31 |
| BE687980A (en)) | 1967-04-07 |
| AT270090B (de) | 1969-04-10 |
| OA02150A (fr) | 1970-05-05 |
| DK127383B (da) | 1973-10-29 |
| FI45188C (fi) | 1972-04-10 |
| FR1496285A (fr) | 1967-09-29 |
| SU374817A3 (en)) | 1973-03-20 |
| AT277481B (de) | 1969-12-29 |
| YU34028B (en) | 1978-10-31 |
| AT275750B (de) | 1969-11-10 |
| AT287927B (de) | 1971-02-10 |
| YU186366A (en) | 1978-05-15 |
| NO119317B (en)) | 1970-05-04 |
| BR6683492D0 (pt) | 1973-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1239692B (de) | Verfahren zur Herstellung von 3-(alpha-Arylalkyl)-sydnoniminen, ihren Salzen und N-Acylderivaten | |
| DE946804C (de) | Verfahren zur Herstellung von schwefelhaltigen Abkoemmlingen der Barbitursaeure | |
| CH471064A (de) | Verfahren zur Herstellung von Estern von a-Alkylthyroninderivaten | |
| DE2304054A1 (de) | Verfahren zur gewinnung von dpenicillamin | |
| EP0672647B1 (de) | Verfahren zur Herstellung von Aminoethylglycin | |
| DE1493567C3 (de) | Ester von alpha-Alkylthyroxinderivaten und Verfahren zu ihrer Herstellung | |
| DE2931255C2 (en)) | ||
| DE2923298C2 (en)) | ||
| DE2404924A1 (de) | Ergolinderivate | |
| DE1493567B2 (de) | Ester von alpha-Alkylthyroxinderivaten und Verfahren zu ihrer Herstellu ng | |
| DE1670539C3 (de) | Diacylthiamine und Verfahren zu deren Herstellung | |
| AT244987B (de) | Verfahren zur Herstellung neuer Indolylalkylguanidin-Derivate | |
| AT384221B (de) | Verfahren zur herstellung von neuen 3-substituierten tetrahydro-pyrrolo(1,2-a) pyrimidin-derivaten sowie von deren saeureadditions- und quaternaeren salzen | |
| AT269864B (de) | Verfahren zur Herstellung von neuen Pyrrylaminoketonderivaten und ihren Salzen | |
| AT215417B (de) | Verfahren zur Herstellung neuer N-Carbalkoxy- bzw. -aralkoxyalkyl-β-(3,4-dihydroxyphenyl)-β-hydroxyäthylamine und deren Salze | |
| CH624396A5 (en)) | ||
| DE2312256C3 (de) | 5-Pyrazol-essigsäurederivate, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Mittel | |
| DE1620490C (de) | Pyrazolon-(5)-derivate und ein Verfahren zu ihrer Herstellung | |
| DE1593925C (de) | Nitrosohydroxylaminopropionsäurederivate und Verfahren zu ihrer Herstellung | |
| AT333771B (de) | Verfahren zur herstellung von neuen 2-alkyl-4(3h)-pteridinonen und von deren salzen | |
| AT261592B (de) | Verfahren zur Herstellung L-(-)-α-Methyl-β-(3,4-dihydroxyphenyl)-alanin | |
| AT315870B (de) | Verfahren zur Herstellung von neuen Adenin-Derivaten und von deren Salzen | |
| DE2911296C2 (de) | (+)-(3-Methyl-4-oxo-5- piperidinothiazolidin-2-yliden)-essigsäureester, Verfahren zu deren Herstellung und deren Verwendung bei der Bekämpfung der Hypertonie | |
| DE1695381B2 (de) | Phthalazino eckige klammer auf 2,3-b eckige klammer zu phthalazine und ein verfahren zu ihrer herstellung | |
| DE1670143A1 (de) | 2-[Indolinyl (1')-Methyl]-imidazolin(2) und dessen Salze sowie Verfahren zur Herstellung dieser Verbindungen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |