30341-92-5

Usage

Uses

Used in Pharmaceutical Industry:
ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER is used as a potential therapeutic agent for the treatment of medical conditions such as migraines and Parkinson's disease. Its unique structure and properties allow it to target specific receptors and pathways involved in these conditions, offering new avenues for treatment and management.
Used in Research and Development:
ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER is used as a subject of research for its potential psychoactive effects. Its psychotropic properties make it a candidate for studies exploring its potential as a recreational drug or psychedelic substance. Further research is needed to fully understand its effects and potential applications in this area.
Used in Drug Delivery Systems:
As ERGOLINE-8-CARBOXYLIC ACID METHYL ESTER continues to be studied for its medicinal properties, drug delivery systems may be developed to enhance its bioavailability, efficacy, and targeted delivery to specific tissues or cells. This could improve the therapeutic outcomes and reduce potential side effects associated with its use in treating various medical conditions.

InChI:InChI=1/C16H18N2O2/c1-20-16(19)10-5-12-11-3-2-4-13-15(11)9(7-17-13)6-14(12)18-8-10/h2-4,7,10,12,14,17-18H,5-6,8H2,1H3/t10-,12?,14-/m1/s1

Synthetic route

9-methyl 7-(2,2,2-trichloroethyl) (6aR,9R,10aR)-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxylate (80993-64-2) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
With acetic acid; zinc for 60h; Heating;	72%
With zinc In methanol; acetic acid at 20℃; for 1.08333h;	71%

D-6-cyano-8β-methoxycarbonylergoline (51260-62-9) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
With hydrogen; W-7 Raney Ni In N,N-dimethyl-formamide
aluminum nickel In N,N-dimethyl-formamide

9,10-dihydrolysergic acid (5878-43-3) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2SO4 2: CH2Cl2 3: H2 / W-7 Raney Ni / dimethylformamide View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid / 15 h / 20 °C 2: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 3: zinc / methanol; acetic acid / 1.08 h / 20 °C View Scheme

9,10-dihydrolysergic acid methyl ester (3006-19-7, 5143-94-2, 35470-53-2, 77842-02-5, 87247-99-2, 96648-31-6, 96648-32-7) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: CH2Cl2 2: H2 / W-7 Raney Ni / dimethylformamide View Scheme
Multi-step reaction with 2 steps 1: 90 percent / CH2Cl2 / 48 h / Heating 2: 72 percent / Zn, AcOH / 60 h / Heating View Scheme
Multi-step reaction with 2 steps 1: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 2: zinc / methanol; acetic acid / 1.08 h / 20 °C View Scheme

methanol (67-56-1) + ergoline-8-carboxylic acid → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
With sulfuric acid

Dihydroergocryptine (25447-66-9) → methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide; sodium dithionite / water / 4 h / Reflux 2: sulfuric acid / 15 h / 20 °C 3: dmap / dichloromethane / 16 h / Reflux; Inert atmosphere 4: zinc / methanol; acetic acid / 1.08 h / 20 °C View Scheme

di-tert-butyl dicarbonate (24424-99-5) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 1,6-di(tert-butoxycarbonyl)-ergoline-8β-carboxylic acid methyl ester

Conditions	Yield
With triethylamine; dmap In dichloromethane at 40℃; for 5h;	95.2%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + allyl bromide (106-95-6) → methyl (6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (72821-79-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 35℃; for 2.5h;	94%
With potassium carbonate In N,N-dimethyl-formamide	80%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + phenyl isocyanate (103-71-9) → (4aR,8R,9aR)-methyl 6-(phenylcarbamoyl)-1,4,4a,6,7,8,9,9a-octahydroindolo[1,14-fg]quinoline-8-carboxylate (1624289-33-3)

Conditions	Yield
In dichloromethane at 20℃;	90%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + ethyl iodide (75-03-6) → 6-nor-6-n-ethyl-9,10-dihydrolysergic acid methyl ester (30341-94-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h;	75%
With potassium carbonate In N,N-dimethyl-formamide

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + propyl bromide (106-94-5) → 6-nor-6-n-propyl-9,10-dihydrolysergic acid methyl ester (63719-09-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	73%

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + 1-iodo-propane (107-08-4) → 6-nor-6-n-propyl-9,10-dihydrolysergic acid methyl ester (63719-09-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h;	47%
With potassium carbonate In N,N-dimethyl-formamide
With potassium carbonate In methanol; chloroform; N,N-dimethyl-formamide

ethyl bromide (74-96-4) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 6-nor-6-n-ethyl-9,10-dihydrolysergic acid methyl ester (30341-94-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide

Isobutyl iodide (513-38-2) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-7-Isobutyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester

pivaloyl chloride (3282-30-2) + methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-7-(2,2-Dimethyl-propionyl)-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (5R,8S,10R)-8-methoxycarbonylergoline (86891-09-0)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at 0℃; for 2h; Product distribution; other time;	16.6 % Chromat.

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) + cyclopropanecarboxylic acid chloride (4023-34-1) → (6aR,9R,10aR)-7-Cyclopropanecarbonyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester (82842-05-5)

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6-ethyl-ergolin-8-yl)-methanol (63719-20-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3 / dimethylformamide 2: 94 percent / LiAlH4 / tetrahydrofuran / 0.5 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → D-6-propyl-8β-hydroxymethylergoline (63719-21-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-9-Imidazol-1-ylmethyl-7-propyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 90 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (5R,8R,10R)-6-propyl-8-(1,2,4-triazol-4-ylmethyl)ergoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 80 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → Toluene-4-sulfonic acid (6aR,9R,10aR)-7-ethyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-ylmethyl ester (74627-23-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3 / dimethylformamide 2: 94 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 81 percent / pyridine / 3 h / Ambient temperature View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → Toluene-4-sulfonic acid (6aR,9R,10aR)-7-propyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-ylmethyl ester (79675-18-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (6aR,9R,10aR)-7-Ethyl-9-[1,2,4]triazol-1-ylmethyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 94 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 81 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 90 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → (5R,8R,10R)-6-propyl-8-(1,2,4-triazol-1-ylmethyl)ergoline

Conditions	Yield
Multi-step reaction with 4 steps 1: K2CO3 / dimethylformamide 2: 96 percent / LiAlH4 / tetrahydrofuran / 0.5 h 3: 85 percent / pyridine / 3 h / Ambient temperature 4: 1.) NaH / 1.) DMF, 2.) DMF, 80 deg C, 2 h View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → ((6aR,9R,10aR)-7-Isobutyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-methanol

Conditions	Yield
Multi-step reaction with 2 steps 2: NaBH4 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → [(6aR,9R,10aR)-7-allyl-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-yl]methanol (72821-88-6)

Conditions	Yield
Multi-step reaction with 2 steps 2: NaBH4 View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2.5 h / 35 °C 2: lithium aluminium tetrahydride / tetrahydrofuran; diethyl ether / 0.75 h / Inert atmosphere; Cooling with ice View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 6-cyclopropyl-methylergoline-8β-methanol (82842-03-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: LiAlH4 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 6-neopentylergoline-8β-methanol (88133-33-9)

Conditions	Yield
Multi-step reaction with 2 steps 2: LiAlH4 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 2-Cyano-3-((6aR,9S,10aR)-7-isobutyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-propionamide

Conditions	Yield
Multi-step reaction with 5 steps 2: NaBH4 5: NH3 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 3-((6aR,9S,10aR)-7-Allyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl)-2-cyano-propionamide

Conditions	Yield
Multi-step reaction with 5 steps 2: NaBH4 5: NH3 View Scheme

methyl (6aR,9R,10aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate (30341-92-5) → 2-Cyano-3-[(6aR,9S,10aR)-7-(2,2-dimethyl-propyl)-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinolin-9-yl]-propionamide

Conditions	Yield
Multi-step reaction with 5 steps 2: LiAlH4 5: NH3 View Scheme

Upstream product

• 67-56-1 methanol 
• 109698-20-6 4,5-dihydro-indolo[4,3-fg]quinoline-9-carboxylic acid ethyl ester 
• 3006-19-7 9,10-dihydrolysergic acid methyl ester 
• 25447-66-9 Dihydroergocryptine 
• 5878-43-3 9,10-dihydrolysergic acid 
• 51260-62-9 D-6-cyano-8β-methoxycarbonylergoline 
• 80993-64-2 9-methyl 7-(2,2,2-trichloroethyl) (6aR,9R,10aR)-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxylate 
• 109601-99-2 4-acetyl-4,5-dihydro-indolo[4,3-fg]quinoline-9-carbonitrile 

Downstream Products

• 3006-19-7 rac-6-methyl-5α-ergoline-8β-carboxylic acid methyl ester 
• 3006-19-7 rac-6-methyl-5α-ergoline-8α-carboxylic acid methyl ester 
• 2481-70-1 rac-6-methyl-5α-ergoline-8α-carboxylic acid 
• 1752-45-0 6-methyl-5α-ergoline-8α-carboxylic acid hydrazide 
• 1752-45-0 rac-6-methyl-5α-ergoline-8α-carboxylic acid hydrazide 
• 30341-94-7 rac-6-ethyl-ergoline-8β-carboxylic acid methyl ester 
• 63719-09-5 rac-6-propyl-ergoline-8β-carboxylic acid methyl ester 
• 2481-70-1 rac-9,10-dihydrolysergic acid 
• 3006-19-7 methyl (6aRS,9RS,10aSR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo<4,3-fg>quinoline-9-carboxylate 
• 2481-70-1 rac-6-methyl-ergoline-8α-carboxylic acid 
• 3006-19-7 methyl (6aRS,9SS,10aSR)-7-methyl-4,6,6a,7,8,9,10,10a-octahydroindolo<4,3-fg>quinoline-9-carboxylate 
• 2481-70-1 9,10-Dihydrolysergsaeure 
• 5878-43-3 9,10-dihydrolysergic acid 
• 1752-45-0 rac-6-methyl-ergoline-8α-carboxylic acid hydrazide 

Relevant academic research and scientific papers

Synthesis of European pharmacopoeial impurities A, B, C, and D of cabergoline

For the use of analytics, European pharmacopoeial impurities A, B, C, and D of cabergoline were synthesized. Ergocryptine was chosen as a starting material and synthesis was accomplished via two approaches, different in length and stereochemical outcome. A longer, indirect approach was realized through otherwise problematic oxidations of the 9,10-dihidrolysergol derivative, to the corresponding aldehyde and carboxylic acid. This was achieved by the use of activated DMSO and a Pinnick oxidation sequence. All four synthesized impurities are used as analytical standards in cabergoline manufacturing processes.

Ergoline derivatives as highly potent and selective antagonists at the somatostatin sst1 receptor

Non-peptidic compounds containing the octahydro-indolo[4,3-fg]quinoline (ergoline) structural element have been optimized into derivatives with high affinity (pKd r sst1 > 9) and selectivity (>1000-fold for h sst1 over h sst2-h sst5) for the somatostatin sst1 receptor. In functional assays, these ergolines act as antagonists at human recombinant sst1 receptors. Pharmacokinetic studies in rodents reveal good oral bioavailability and brain penetration for some of these compounds.

Synthesis and structure-activity relationships of new (5R,8R,10R)-ergoline derivatives with antihypertensive or dopaminergic activity

A series of new (5R,8R,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were tested in conscious spontaneously hypertensive rats and in rats with unilateral 6- hydroxydopamine-induced lesions of the substantia nigra. (5R,8R,10R)-6- Alkyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-methylergoline (4s, maleate: BAM-1110) exhibited potent dopaminergic activity, about 18- fold greater than that of bromocriptine mesylate. (5R,8R,10R)-8-(1,2,4- Triazol-1-ylmethyl)-6-propylergoline (8b, fumarate: BAM-1602) showed extremely potent dopaminergic activity, being about 220 and 1.15 times more active than bromocriptine mesylate and pergolide mesylate, respectively. Several compounds exhibited potent antihypertensive activity. Structure- activity relationships for antihypertensive and dopaminergic activities are discussed.

6-N-Propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds

6-n-Propyl (ethyl or allyl)-8β-methoxy-(methylsulfinyl, methylsulfonyl, or methylmercapto) methylergolines, 8-ergolenes or 9-ergolenes, useful as prolactin inhibitors and in the treatment of Parkinsonism.