IE49076B1 - Process for the preparation of brominated ergot alkaloids - Google Patents
Process for the preparation of brominated ergot alkaloidsInfo
- Publication number
- IE49076B1 IE49076B1 IE1832/79A IE183279A IE49076B1 IE 49076 B1 IE49076 B1 IE 49076B1 IE 1832/79 A IE1832/79 A IE 1832/79A IE 183279 A IE183279 A IE 183279A IE 49076 B1 IE49076 B1 IE 49076B1
- Authority
- IE
- Ireland
- Prior art keywords
- bromo
- alkyl
- methyl
- chloro
- pyridazine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 10
- 229960003133 ergot alkaloid Drugs 0.000 title description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 9
- 229950001817 alpha-ergocryptine Drugs 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 4
- 125000003368 amide group Chemical group 0.000 abstract 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 3
- HLPWNGZWBGZKPV-UHFFFAOYSA-N 3-bromo-6-chloro-2-methylimidazo[1,2-b]pyridazine dihydrobromide Chemical compound Br.Br.C1=CC(Cl)=NN2C(Br)=C(C)N=C21 HLPWNGZWBGZKPV-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229960004704 dihydroergotamine Drugs 0.000 description 2
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine 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]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- QYAPHLRPFNSDNH-MRFRVZCGSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O QYAPHLRPFNSDNH-MRFRVZCGSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-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
- VKRAXSZEDRWLAG-SJKOYZFVSA-N 2-bromo-lsd Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=C(Br)NC3=C1 VKRAXSZEDRWLAG-SJKOYZFVSA-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
- LHUSNTKCDGCCOB-UHFFFAOYSA-N 3-bromo-6-chloro-2-methylimidazo[1,2-b]pyridazine Chemical compound C1=CC(Cl)=NN2C(Br)=C(C)N=C21 LHUSNTKCDGCCOB-UHFFFAOYSA-N 0.000 description 1
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 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
- 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 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- -1 ergot alkaloids Chemical class 0.000 description 1
- 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 description 1
- 229960004943 ergotamine Drugs 0.000 description 1
- 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 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU2268/78A YU39849B (en) | 1978-09-26 | 1978-09-26 | Process for preparing 2-bromo-ergolene and 2-bromo-ergoline compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE791832L IE791832L (en) | 1980-03-26 |
| IE49076B1 true IE49076B1 (en) | 1985-07-24 |
Family
ID=25557457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1832/79A IE49076B1 (en) | 1978-09-26 | 1979-09-26 | Process for the preparation of brominated ergot alkaloids |
Country Status (45)
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU196394B (en) * | 1986-06-27 | 1988-11-28 | Richter Gedeon Vegyeszet | Process for preparing 2-halogenated ergoline derivatives |
| CN104016982A (zh) * | 2014-06-26 | 2014-09-03 | 华东理工大学 | 一种利用大孔树脂制备烟曲霉文丙的方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH507249A (de) * | 1968-05-31 | 1971-05-15 | Sandoz Ag | Verfahren zur Herstellung von 2-Brom-a-ergokryptin |
| YU39786B (en) * | 1976-12-23 | 1985-04-30 | Lek Tovarna Farmacevtskih | Process for preparing 2-bromo-alfa-ergocriptine |
| YU216177A (en) * | 1977-09-09 | 1984-02-29 | Rudolf Rucman | Process for preparing 2-bromo ergosine |
-
1978
- 1978-09-26 YU YU2268/78A patent/YU39849B/xx unknown
-
1979
- 1979-09-19 IT IT7950300A patent/IT1206988B/it active
- 1979-09-20 CH CH8492/79A patent/CH649769A5/de not_active IP Right Cessation
- 1979-09-21 DE DE19792938313 patent/DE2938313A1/de active Granted
- 1979-09-24 PT PT70216A patent/PT70216A/pt unknown
- 1979-09-24 BE BE1/9540A patent/BE878953A/fr not_active IP Right Cessation
- 1979-09-24 CY CY1240A patent/CY1240A/xx unknown
- 1979-09-24 FI FI792957A patent/FI66185C/fi not_active IP Right Cessation
- 1979-09-24 GB GB7932989A patent/GB2031890B/en not_active Expired
- 1979-09-24 LU LU81714A patent/LU81714A1/fr unknown
- 1979-09-24 GR GR60103A patent/GR73015B/el unknown
- 1979-09-24 AT AT0624379A patent/AT376439B/de not_active IP Right Cessation
- 1979-09-24 MX MX798393U patent/MX5864E/es unknown
- 1979-09-24 DD DD79215747A patent/DD146048A5/de not_active IP Right Cessation
- 1979-09-24 IS IS2512A patent/IS2512A7/is unknown
- 1979-09-24 NZ NZ191643A patent/NZ191643A/xx unknown
- 1979-09-24 AR AR278180A patent/AR223496A1/es active
- 1979-09-24 NO NO793058A patent/NO153852C/no unknown
- 1979-09-24 HU HU79SA3200A patent/HU182576B/hu unknown
- 1979-09-25 MA MA18795A patent/MA18595A1/fr unknown
- 1979-09-25 BG BG044956A patent/BG32716A3/xx unknown
- 1979-09-25 PL PL1979218497A patent/PL120388B1/pl unknown
- 1979-09-25 DK DK401979A patent/DK149956C/da not_active IP Right Cessation
- 1979-09-25 SU SU792818045A patent/SU1178324A3/ru active
- 1979-09-25 IL IL58318A patent/IL58318A/xx unknown
- 1979-09-25 SE SE7907942A patent/SE433497B/sv not_active IP Right Cessation
- 1979-09-25 AU AU51172/79A patent/AU529462B2/en not_active Ceased
- 1979-09-25 ES ES484445A patent/ES484445A1/es not_active Expired
- 1979-09-25 FR FR7923816A patent/FR2437411A1/fr active Granted
- 1979-09-25 UA UA2818045A patent/UA7078A1/uk unknown
- 1979-09-25 NL NL7907122A patent/NL7907122A/nl not_active Application Discontinuation
- 1979-09-25 CS CS796471A patent/CS215027B2/cs unknown
- 1979-09-25 JP JP12373279A patent/JPS5545699A/ja active Granted
- 1979-09-25 PH PH23062A patent/PH14986A/en unknown
- 1979-09-25 RO RO7998760A patent/RO78936A/fr unknown
- 1979-09-25 EG EG566/79A patent/EG14277A/xx active
- 1979-09-26 BR BR7906175A patent/BR7906175A/pt unknown
- 1979-09-26 IE IE1832/79A patent/IE49076B1/en not_active IP Right Cessation
- 1979-09-26 ZA ZA00795110A patent/ZA795110B/xx unknown
- 1979-09-26 CA CA336,448A patent/CA1128038A/fr not_active Expired
-
1980
- 1980-09-23 IN IN1077/CAL/80A patent/IN154914B/en unknown
-
1984
- 1984-03-05 SG SG204/84A patent/SG20484G/en unknown
- 1984-04-12 KE KE3392A patent/KE3392A/xx unknown
- 1984-06-14 HK HK491/84A patent/HK49184A/xx not_active IP Right Cessation
-
1985
- 1985-12-30 MY MY131/85A patent/MY8500131A/xx unknown
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |