PL64158B1 - - Google Patents

Info

Publication number

PL64158B1

PL64158B1 PL132900A PL13290069A PL64158B1 PL 64158 B1 PL64158 B1 PL 64158B1 PL 132900 A PL132900 A PL 132900A PL 13290069 A PL13290069 A PL 13290069A PL 64158 B1 PL64158 B1 PL 64158B1

Authority

PL

Poland

Prior art keywords

ergotamine

alkaloids

group

grams

heated

Prior art date

1969-04-11

Links

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• Global Dossier
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• 229960004943 ergotamine Drugs 0.000 claims description 26
• OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 claims description 26
• XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 claims description 26
• 229930013930 alkaloid Natural products 0.000 claims description 15
• 238000000034 method Methods 0.000 claims description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
• 239000012452 mother liquor Substances 0.000 claims description 6
• 238000010438 heat treatment Methods 0.000 claims description 5
• 238000010992 reflux Methods 0.000 claims description 5
• OWEUDBYTKOYTAD-MKTPKCENSA-N ergocristine Chemical class C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@@H]1C=C2C3=CC=CC4=NC=C([C]34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 OWEUDBYTKOYTAD-MKTPKCENSA-N 0.000 claims description 4
• 238000006317 isomerization reaction Methods 0.000 claims description 4
• 230000020477 pH reduction Effects 0.000 claims description 2
• 239000013078 crystal Substances 0.000 claims 1
• 229960003133 ergot alkaloid Drugs 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
• 238000000354 decomposition reaction Methods 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• YDOTUXAWKBPQJW-UHFFFAOYSA-N ergocryptine Chemical compound 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 5
• 238000000926 separation method Methods 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• HEFIYUQVAZFDEE-UHFFFAOYSA-N ergocristinine Natural products N12C(=O)C(C(C)C)(NC(=O)C3C=C4C=5C=CC=C6NC=C(C=56)CC4N(C)C3)OC2(O)C2CCCN2C(=O)C1CC1=CC=CC=C1 HEFIYUQVAZFDEE-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• VCCNKWWXYVWTLT-CYZBKYQRSA-N 7-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCCNKWWXYVWTLT-CYZBKYQRSA-N 0.000 description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
• 229950001817 alpha-ergocryptine Drugs 0.000 description 3
• 229960001903 ergotamine tartrate Drugs 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 239000012535 impurity Substances 0.000 description 3
• 239000000047 product Substances 0.000 description 3
• 229910021653 sulphate ion Inorganic materials 0.000 description 3
• 239000011975 tartaric acid Substances 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 229960000583 acetic acid Drugs 0.000 description 2
• 239000003463 adsorbent Substances 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• YDOTUXAWKBPQJW-NSLWYYNWSA-N alpha-ergocryptine 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-NSLWYYNWSA-N 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 150000003839 salts Chemical class 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• SCTIUNDDSVXTLN-GRMMLOPMSA-N ergocristine phosphate Chemical compound OP(O)(O)=O.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@@H]1C=C2C=3C=CC=C4NC=C(C=34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 SCTIUNDDSVXTLN-GRMMLOPMSA-N 0.000 description 1
• HEFIYUQVAZFDEE-NASJTFDLSA-N ergocristinine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@H]1C=C2C=3C=CC=C4NC=C(C=34)C[C@H]2N(C)C1)C(C)C)C1=CC=CC=C1 HEFIYUQVAZFDEE-NASJTFDLSA-N 0.000 description 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 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical class O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1