DD264430A5 - Verfahren zur herstellung von 2-brom-2-ergokryptin - Google Patents

Verfahren zur herstellung von 2-brom-2-ergokryptin Download PDF

Info

Publication number: DD264430A5
Authority: DD; German Democratic Republic
Prior art keywords: bromo; ergokryptin; acid addition; halogenation; mixture
Prior art date: 1986-06-27

Application number

DD87304197A

Other languages

German (de)

English (en)

Inventor

Gabor Megyeri

Tibor Keve

Lajos Kovacs Jr

Bela Stefko

Erik Bogsch

Anna Kassai

Ferenc Trischler

Gabor Szepesi

Maria Gazdag

Original Assignee

��@��@��@��@��Kk��

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.)

1986-06-27

Filing date

1987-06-26

Publication date

1989-02-01

1987-06-26 Application filed by ��@��@��@��@��Kk�� filed Critical ��@��@��@��@��Kk��

1989-02-01 Publication of DD264430A5 publication Critical patent/DD264430A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 30
238000002360 preparation method Methods 0.000 title claims abstract description 14
239000002253 acid Substances 0.000 claims abstract description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 17
229950001817 alpha-ergocryptine Drugs 0.000 claims abstract description 15
150000003839 salts Chemical class 0.000 claims abstract description 15
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 11
239000000126 substance Substances 0.000 claims abstract description 8
229910000042 hydrogen bromide Inorganic materials 0.000 claims abstract description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 4
VQPFDLRNOCQMSN-UHFFFAOYSA-N bromosilane Chemical compound Br[SiH3] VQPFDLRNOCQMSN-UHFFFAOYSA-N 0.000 claims abstract description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 3
239000001257 hydrogen Substances 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
229960003133 ergot alkaloid Drugs 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
238000004587 chromatography analysis Methods 0.000 claims description 4
230000002140 halogenating effect Effects 0.000 claims description 3
VSCMNSZBNLOXNR-UHFFFAOYSA-N bromo(triphenyl)silane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(Br)C1=CC=CC=C1 VSCMNSZBNLOXNR-UHFFFAOYSA-N 0.000 claims 1
YREISLCRUMOYAY-IIPCNOPRSA-N ergometrine maleate Chemical class OC(=O)\C=C/C(O)=O.C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)C)C2)=C3C2=CNC3=C1 YREISLCRUMOYAY-IIPCNOPRSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 29
238000005658 halogenation reaction Methods 0.000 abstract description 13
230000026030 halogenation Effects 0.000 abstract description 11
230000035484 reaction time Effects 0.000 abstract description 3
208000031424 hyperprolactinemia Diseases 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
229930013930 alkaloid Natural products 0.000 description 10
150000001875 compounds Chemical class 0.000 description 10
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
229960001760 dimethyl sulfoxide Drugs 0.000 description 8
150000003797 alkaloid derivatives Chemical class 0.000 description 7
239000000047 product Substances 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 6
239000013078 crystal Substances 0.000 description 6
AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical group O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
238000005893 bromination reaction Methods 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
230000031709 bromination Effects 0.000 description 4
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 4
229910052736 halogen Inorganic materials 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
NESVMZOPWPCFAU-UHFFFAOYSA-N Ergoclavinine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C)C2)=C3C2=CNC3=C1 NESVMZOPWPCFAU-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
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 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000006345 epimerization reaction Methods 0.000 description 3
NESVMZOPWPCFAU-ZPRCMDFASA-N ergosine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C)C2)=C3C2=CNC3=C1 NESVMZOPWPCFAU-ZPRCMDFASA-N 0.000 description 3
229930015720 peptide alkaloid Natural products 0.000 description 3
235000002906 tartaric acid Nutrition 0.000 description 3
239000011975 tartaric acid Substances 0.000 description 3
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000005660 chlorination reaction Methods 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000007789 gas Substances 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
239000005457 ice water Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000007017 scission Effects 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
GJNCXCPHNRATIQ-UHFFFAOYSA-N 1-bromoazepan-2-one Chemical compound BrN1CCCCCC1=O GJNCXCPHNRATIQ-UHFFFAOYSA-N 0.000 description 1
QRADPXNAURXMSB-UHFFFAOYSA-N 2-bromo-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=CC=C2S(=O)(=O)N(Br)C(=O)C2=C1 QRADPXNAURXMSB-UHFFFAOYSA-N 0.000 description 1
RWKSIKQHBHYHCA-UHFFFAOYSA-N 2-n-bromobenzene-1,2-dicarboxamide Chemical compound NC(=O)C1=CC=CC=C1C(=O)NBr RWKSIKQHBHYHCA-UHFFFAOYSA-N 0.000 description 1
QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
YDOTUXAWKBPQJW-JJANYQHSSA-N 919k69s85n Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-JJANYQHSSA-N 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
-1 Bromo-O Chemical class 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical class [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
102000002322 Egg Proteins Human genes 0.000 description 1
108010000912 Egg Proteins Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000003463 adsorbent Substances 0.000 description 1
YDOTUXAWKBPQJW-UHFFFAOYSA-N alpha-Ergocryptinine Natural products C1=CC(C=2C(N(C)CC(C=2)C(=O)NC2(C(=O)N3C(C(N4CCCC4C3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=CNC3=C1 YDOTUXAWKBPQJW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
238000009739 binding Methods 0.000 description 1
230000027455 binding Effects 0.000 description 1
GSQACUNMFGRAKY-UHFFFAOYSA-N bromine;1,4-dioxane Chemical compound [Br].C1COCCO1 GSQACUNMFGRAKY-UHFFFAOYSA-N 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
MNKYQPOFRKPUAE-UHFFFAOYSA-N chloro(triphenyl)silane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 MNKYQPOFRKPUAE-UHFFFAOYSA-N 0.000 description 1
ACTAPAGNZPZLEF-UHFFFAOYSA-N chloro(tripropyl)silane Chemical compound CCC[Si](Cl)(CCC)CCC ACTAPAGNZPZLEF-UHFFFAOYSA-N 0.000 description 1
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical group C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000000151 deposition Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
235000014103 egg white Nutrition 0.000 description 1
210000000969 egg white Anatomy 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000012456 homogeneous solution Substances 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
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
239000003999 initiator Substances 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
150000002497 iodine compounds Chemical class 0.000 description 1
IDIOJRGTRFRIJL-UHFFFAOYSA-N iodosilane Chemical compound I[SiH3] IDIOJRGTRFRIJL-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
238000002156 mixing Methods 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000002994 raw material Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
238000007873 sieving Methods 0.000 description 1
150000004756 silanes Chemical class 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
JSQJUDVTRRCSRU-UHFFFAOYSA-N tributyl(chloro)silane Chemical compound CCCC[Si](Cl)(CCCC)CCCC JSQJUDVTRRCSRU-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/04—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid 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 in position 8
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

DD87304197A 1986-06-27 1987-06-26 Verfahren zur herstellung von 2-brom-2-ergokryptin DD264430A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
HU862690A HU196394B (en)	1986-06-27	1986-06-27	Process for preparing 2-halogenated ergoline derivatives

Publications (1)

Publication Number	Publication Date
DD264430A5 true DD264430A5 (de)	1989-02-01

Family

ID=10960659

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD87304197A DD264430A5 (de)	1986-06-27	1987-06-26	Verfahren zur herstellung von 2-brom-2-ergokryptin

Country Status (19)

Country	Link
US (1)	US4816587A (cs)
EP (1)	EP0251732B1 (cs)
JP (1)	JPH085879B2 (cs)
AR (1)	AR243194A1 (cs)
AT (1)	ATE88705T1 (cs)
AU (1)	AU597673B2 (cs)
BG (1)	BG48811A3 (cs)
CA (1)	CA1301163C (cs)
CS (1)	CS264295B2 (cs)
DD (1)	DD264430A5 (cs)
DE (1)	DE3785613T2 (cs)
DK (1)	DK328687A (cs)
ES (1)	ES2054672T3 (cs)
FI (1)	FI89048C (cs)
HU (1)	HU196394B (cs)
PL (1)	PL151562B1 (cs)
SU (1)	SU1528320A3 (cs)
UA (1)	UA5571A1 (cs)
YU (1)	YU46557B (cs)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU196598B (en) *	1986-04-25	1988-12-28	Richter Gedeon Vegyeszet	Process for producing 1- and/or 8-substituted 2-halogenated ergoline derivatives and pharmaceutics comprising such compounds
DE4033496A1 (de) *	1990-10-20	1992-04-23	Sandoz Ag	Neue ergolinderivate, ihre herstellung und verwendung
DE69419721T2 (de) *	1993-01-12	2000-04-27	Biogen, Inc.	Rekombinante anti-vla4 antikörpermoleküle
US6723550B1 (en)	1997-07-15	2004-04-20	Genencor International, Inc.	Proteases from gram-positive organisms
US20030157642A1 (en) *	1997-07-15	2003-08-21	Caldwell Robert M.	Increasing production of proteins in gram-positive microorganisms
US6521421B1 (en) *	1997-07-16	2003-02-18	Genencor International, Inc.	Expression vectors encoding Bacillus subtilis disulfide bond isomerase and methods of secreting proteins in gram-positive microorganisms using the same
US6521440B1 (en)	1997-09-15	2003-02-18	Genencor International, Inc.	Proteases from gram-positive organisms
US6316241B1 (en) *	1997-11-20	2001-11-13	Genencor International, Inc.	Alpha/beta hydrolase-fold enzymes
FR2786099B1 (fr) *	1998-11-24	2000-12-29	Aventis Laboratoire	Nouvelle application therapeutique de la 1,6-dimethyl-8beta- hydroxymethyl-10alpha-methoxyergoline
WO2002072787A2 (en) *	2001-03-13	2002-09-19	Sierra Sciences, Inc.	Telomerase expression repressor proteins and methods of using the same
JP2004537976A (ja)	2001-03-15	2004-12-24	インターナショナルバイオイムンシステムズ，インコーポレーテッド	膵癌のモノクローナル抗体治療
DE60236089D1 (de)	2001-07-02	2010-06-02	Sekisui Medical Co Ltd	Latex-trägerpartikel für ein testreagenz, und testreagenz
CA2478458A1 (en) *	2004-08-20	2006-02-20	Michael Panzara	Treatment of pediatric multiple sclerosis
RU2274640C1 (ru) *	2004-09-15	2006-04-20	Всероссийский научно-исследовательский институт лекарственных и ароматических растений ("ВИЛАР")	СПОСОБ БРОМИРОВАНИЯ α И β-ЭРГОКРИПТИНОВ
HRP20171045T1 (hr)	2010-04-16	2017-10-06	Biogen Ma Inc.	Protutijela anti-vla-4
US8889768B2 (en)	2010-06-11	2014-11-18	Basf Se	Laser-transparent PBT with organic additives
CN102939195B (zh)	2010-06-11	2015-12-02	巴斯夫欧洲公司	包含有机添加剂的激光透明性pbt
CN105560244B (zh) *	2014-10-10	2019-01-11	上海交通大学	一种γ-分泌酶抑制剂及其应用
CN107428820B (zh)	2014-11-19	2022-03-22	阿克松神经系统科学公司	在阿尔茨海默氏病中的人源化tau抗体
JP6849678B2 (ja)	2016-06-14	2021-03-24	デンカ株式会社	液体試料検査キット用膜担体、液体試料検査キット及び液体試料検査キットの製造方法
ES2912613T3 (es)	2017-03-28	2022-05-26	Denka Company Ltd	Soporte de membrana, kit para probar una muestra líquida usando el mismo, y método de fabricación del mismo
CN110312934B (zh)	2017-03-28	2023-02-17	电化株式会社	膜载体和使用其的液体试样检测试剂盒
CN119080931A (zh)	2018-06-04	2024-12-06	马萨诸塞州渤健公司	具有降低的效应功能的抗vla-4抗体
AU2023267670A1 (en) *	2022-05-12	2024-12-19	The Florida State University Research Foundation, Inc.	Lysergic acid derivatives and methods
WO2024145546A1 (en) *	2022-12-31	2024-07-04	Ceruvia Lifesciences Llc	Process for synthesizing 2-bromolysergic acid diethylamide via controlled bromination of lysergic acid

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3901894A (en) *	1974-06-06	1975-08-26	Lilly Co Eli	8-thiomethylergolines
US3992422A (en) *	1975-08-14	1976-11-16	Schering Corporation	Process for the preparation of 21-halogeno-21-desoxy-17α-acyloxy-20-keto-pregnenes
US4098790A (en) *	1976-09-15	1978-07-04	Eli Lilly And Company	Ergoline chlorination process
YU216177A (en) *	1977-09-09	1984-02-29	Rudolf Rucman	Process for preparing 2-bromo ergosine
US4166182A (en) *	1978-02-08	1979-08-28	Eli Lilly And Company	6-n-propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds
YU39849B (en) *	1978-09-26	1985-04-30	Lek Tovarna Farmacevtskih	Process for preparing 2-bromo-ergolene and 2-bromo-ergoline compounds
HU193317B (en) *	1985-06-12	1987-09-28	Richter Gedeon Vegyeszet	Process for producing 2-bromo-alpha-ergochristin
HU193782B (en) *	1985-06-21	1987-11-30	Richter Gedeon Vegyeszet	Process for producing 2-halogeno-nicergoline derivatives and acid additional salts thereof
HU193780B (en) *	1985-06-21	1987-11-30	Richter Gedeon Vegyeszet	Process for producing 2-halogeno-6-methyl-ergol-9-ene derivatives and acid additional salts thereof
HU196598B (en) *	1986-04-25	1988-12-28	Richter Gedeon Vegyeszet	Process for producing 1- and/or 8-substituted 2-halogenated ergoline derivatives and pharmaceutics comprising such compounds

1986
- 1986-06-27 HU HU862690A patent/HU196394B/hu not_active IP Right Cessation
1987
- 1987-06-05 US US07/058,576 patent/US4816587A/en not_active Expired - Fee Related
- 1987-06-25 YU YU119987A patent/YU46557B/sh unknown
- 1987-06-26 ES ES87305716T patent/ES2054672T3/es not_active Expired - Lifetime
- 1987-06-26 PL PL1987266477A patent/PL151562B1/pl unknown
- 1987-06-26 SU SU874202820A patent/SU1528320A3/ru active
- 1987-06-26 BG BG080325A patent/BG48811A3/xx unknown
- 1987-06-26 UA UA4202820A patent/UA5571A1/uk unknown
- 1987-06-26 DD DD87304197A patent/DD264430A5/de not_active IP Right Cessation
- 1987-06-26 JP JP62157949A patent/JPH085879B2/ja not_active Expired - Lifetime
- 1987-06-26 AT AT87305716T patent/ATE88705T1/de not_active IP Right Cessation
- 1987-06-26 DE DE8787305716T patent/DE3785613T2/de not_active Expired - Fee Related
- 1987-06-26 CA CA000540700A patent/CA1301163C/en not_active Expired - Lifetime
- 1987-06-26 EP EP87305716A patent/EP0251732B1/en not_active Expired - Lifetime
- 1987-06-26 CS CS874791A patent/CS264295B2/cs unknown
- 1987-06-26 AR AR87307983A patent/AR243194A1/es active
- 1987-06-26 DK DK328687A patent/DK328687A/da not_active Application Discontinuation
- 1987-06-26 FI FI872852A patent/FI89048C/fi not_active IP Right Cessation
- 1987-06-26 AU AU74763/87A patent/AU597673B2/en not_active Ceased

Also Published As

Publication number	Publication date
AU597673B2 (en)	1990-06-07
CS479187A2 (en)	1988-09-16
CA1301163C (en)	1992-05-19
YU119987A (en)	1988-06-30
US4816587A (en)	1989-03-28
ES2054672T3 (es)	1994-08-16
AU7476387A (en)	1988-01-07
JPS6314783A (ja)	1988-01-21
CS264295B2 (en)	1989-06-13
DK328687A (da)	1987-12-28
EP0251732A3 (en)	1989-05-10
UA5571A1 (uk)	1994-12-28
ATE88705T1 (de)	1993-05-15
FI89048C (fi)	1993-08-10
DE3785613T2 (de)	1993-08-12
DE3785613D1 (de)	1993-06-03
BG48811A3 (bg)	1991-05-15
JPH085879B2 (ja)	1996-01-24
FI89048B (fi)	1993-04-30
PL151562B1 (en)	1990-09-28
FI872852L (fi)	1987-12-28
HU196394B (en)	1988-11-28
EP0251732B1 (en)	1993-04-28
SU1528320A3 (ru)	1989-12-07
DK328687D0 (da)	1987-06-26
EP0251732A2 (en)	1988-01-07
PL266477A1 (en)	1988-07-21
FI872852A0 (fi)	1987-06-26
HUT44541A (en)	1988-03-28
AR243194A1 (es)	1993-07-30
YU46557B (sh)	1993-11-16

Legal Events

Date	Code	Title	Description
1999-12-09	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
DD264430A5 (de)	1989-02-01	Verfahren zur herstellung von 2-brom-2-ergokryptin
EP0160842B1 (de)	1994-06-22	2-substituierte Ergolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
CH617196A5 (cs)	1980-05-14
EP0118848B1 (de)	1992-02-19	Neue Ergolin-Derivate, Verfahren zu ihrer Herstellung sowie Verwendung als Arzneimittel
DE2025624A1 (de)	1970-12-03	5'-0-Derivate von Ara-cytidin und Verfahren zu ihrer Herstellung
DE2846321A1 (de)	1979-05-31	Verfahren zur herstellung von rifamycinen
DE2335750C3 (de)	1978-10-19	D-6-Methylergolin-derivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel
DE2851312A1 (de)	1979-07-12	Verfahren zur herstellung von 3-jod- und 3-bromrifamycin s
DE3781879T2 (de)	1993-04-08	Anthracyclinderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel.
DE3533675A1 (de)	1987-03-26	Neue 12- und 13-brom-ergolinderivate
DE3619617A1 (de)	1986-12-18	Verfahren zur herstellung von 2-brom-(alpha)-ergokryptin
DE2948116A1 (de)	1980-06-19	Verfahren zur herstellung von apovincaminsaeureester-derivaten
DE3026602C2 (cs)	1990-05-03
DD256133A5 (de)	1988-04-27	Neue 8- bzw. 1,8-substituierte ergolenderivate und verfahren zu ihrer herstellung
DE2640123C3 (de)	1980-09-25	Maleinsäuresalz des 2-Phenyl-6-(l-hydroxy-2-tert.-butylaminoäthyl)-4H-pyrido-(3,2-d)-l,3-dioxins, ein Verfahren zur Herstellung desselben sowie ein Verfahren zur Herstellung von 2-Hydroxymethyl-3hydroxy-6-(l -hydroxy-2-tert.-butylaminoäthyD-pyridin
CH695422A5 (de)	2006-05-15	Verfahren zur Einführung einer 1,2-Doppelbindung bei 3-Oxo-4-azasteroidverbindungen.
DE2527901A1 (de)	1976-01-15	Verfahren zur herstellung von neuen benzodiazepinderivaten
CH649769A5 (de)	1985-06-14	Verfahren zum selektiven bromieren von ergotalkaloiden und verwandten verbindungen.
CH535235A (de)	1973-03-31	Verfahren zur Herstellung neuer reaktionsträger Lysergsäurederivate
AT332568B (de)	1976-10-11	Verfahren zur herstellung eines neuen d-2,6-dimethyl-8-cyano-(carboxamido)-methylergolins und von dessen salzen
EP0286575A2 (de)	1988-10-12	Verfahren zur Herstellung von 2,3Beta-Dihydroergolinen, 2-substituierte 2,3Beta-Dihydroergoline und ihre Verwendung als Arzneimittel
DE1545759C3 (de)	1975-10-02	Vincaleukoblastin-derivate und ein Verfahren zu ihrer Herstellung
LU86486A1 (de)	1986-12-02	Verfahren zur herstellung von 10 -methoxy-6-methylergolin-derivaten und ihren saeureadditionssalzen
DE1795023A1 (de)	1972-01-13	Neue heterocyclische Verbindungen und Verfahren zu ihrer Herstellung
DE2310302A1 (de)	1973-09-20	0 hoch 2,2'-anhydro-1-(beta-darabinofuranosyl)-cytosinderivate und verfahren zu ihrer herstellung